[Frontiers In Bioscience, Scholar, 10, 185-196, January 1, 2018]

Inflammatory biomarkers of coronary heart disease

Hongyu Li1, Kai Sun2, Ruiping Zhao1, Jiang Hu3, Zhiru Hao1, Fei Wang1, Yaojun Lu1, Fu Liu1,Yong Zhang1

1 Department of Cardiology, Baotou Central Hospital, Baotou, China, 2 Department of Radiology,Baotou Central Hospital, Baotou, China, 3 Department of Surgery, Baotou Central Hospital, Baotou, China


1. Abstract
2. Introduction
3. Characteristics of atherosclerosis
4. Inflammation cascade involved the development of atherosclerosis and CHD
5. Predictive inflammatory biomarkers in CHD
5.1. C-reactive protein (CRP)
5.2. Complement
5.3. IL-6
5.4. Serum amyloid A (SAA)
5.5. CD40/CD40 Ligand (CD40L) system
5.6. Myeloperoxidase (MPO)
6. Conclusions
7. Acknowledgments
8. References


Coronary heart disease (CHD) is one of the leading causes of death worldwide. CHD is characterized by formation of arterial plaques which are mainly comprised of lipids, calcium and inflammatory cells. These plaques narrow the lumen of coronary arteries leading to episodic or persistent angina. Rupture of these plaques leads to the formation of thrombus, which as a result of cessation of blood flow, causes myocardial infarct and death. CHD is exacerbated by risk factors including obesity, diabetes mellitus, and hypertension. Diagnosis is established by the level of blood cholesterol, triglycerides and lipoproteins Inflammation is considered significant in the pathogenesis of CHD and for this reason, severity and prognosis of CHD is assessed by the levels of inflammatory biomarkers, including interleukin-6, C-reactive protein (CRP), complement, CD40 and myeloperoxidase (MPO).


CHD is more common in males than females and is characterized by stable or unstable angina, heart failure, irregular heart beats. CHD can lead to myocardial infarction, which is the leading cause of death in developed countries (1-2, 6–10). CHD was the underlying cause of >8.14 million deaths in 2013, a dramatic increase from 5.2 million CHD-associated deaths reported in 1990 (3–5). CHD affects individuals at any age, but becomes significantly more common with age, tripling in incidence in each decade of life. The underlying mechanism of CHD is atherosclerosis of cornonary arteries. Risk factors for CHD include high blood pressure, obesity, diabetes mellitus, increased blood cholesterol, smoking, lack of exercise, poor diet, excessive consumption of alcohol, and depression (11–14). Diagnosis is established by the level of blood cholesterol, triglycerides and lipoproteins (15–16). CHD is characterized by plaques that develop from accumulation of fatty deposits, inflammatory cells and calcification leading to stiffening of arteries (17–19). Gradual narrowing of the lumen leads to ischemia which may cause ventricular arrhythmia and upon closure of the lumen leads to ventricular fibrillation to infarction (20-22).


Atherosclerosis, characterized by hyperlipidemia and inflammation, is a leading cause of morbidity and mortality due to peripheral vascular diseases (23–24). “Atherogenesis” refers to the development of atheromatous plaques, characterized by arterial remodeling as a result of subendothelial accumulation of fatty deposits. An atheromatous plaque develops over several years through a complex series of cellular events that occur within the arterial wall in response to various local factors (25).

Atherogenesis results from endothelial damage by leukocytes infiltrating the arterial wall and fatty deposits (e.g., monocytes, basophils) (26–28). The primary “driver” of this process is considered to be oxidized lipoproteins within the vascular wall. Marginally normal or elevated glucose concentration in blood is also considered to play a major role in this process ). The low-density lipoprotein (LDL) in plasma invades the endothelium and get oxidized by a complex set of biochemical reactions involving enzymes (e.g., Lp-LpA2) and free radicals (33–35). Although, the LDL is considered to be a risk factor for the development of cardiovascular disease, its direct role is not clarified since fatty streaks may disappear from the plaques (30–32). Early atherogenesis is characterized by adherence of circulating monocytes to the endothelial lining. These subsequently migrate to the sub-endothelial space, and upon activation convert to tissue macrophages (29). Chemokines, such as monocyte chemoattractant protein (MCP)-1, recruit monocytes from the bloodstream to arterial walls and platelets adhere to the area of insult (36–37). This phenomenon may be promoted by induction of redox signaling factors, such as E-selectin, P-selectin, vascular cell adhesion molecule (VCAM)-1, as well as macrophage colony-stimulating factor (M-CSF) secreted by endothelial cells and smooth muscle cells which are stimulated by oxidized LDL. The macrophages phagocytose and ingest oxidized LDL and ultimately convert to large “foam cells” which as a result of numerous internal cytoplasmic vesicles and high lipid content appear as fatty streaks under microscope (38-40). Ultimately, the foam cells die, further propagating the inflammatory process. Moreover, in response to cytokines secreted by damaged endothelial cells, smooth muscle cells proliferate and migrate from the tunica media into the intima and covert the fatty streaks to a fibrous capsule (41–43).


Disruption of normal endothelial function favors vasoconstriction through decreased synthesis of NO and increased synthesis of endothelin I and angiotensin II (44–46). Activation of endothelial cells is mediated by the pro-inflammatory cytokines, interleukin (IL)-1β and tumor necrosis factor (TNF)-α. The activation of endothelial cells upregulates E-selectin, VCAM-1 and intercellular adhesion molecule (ICAM)-1, which facilitates the binding of monocytes and T-cells to the endothelium (47–49).

Migration of inflammatory cells into the intima is promoted by chemokines (including MCP-1), (50). Monocytes once within the intima, are transformed into macrophages that express “scavenger receptors” for modified lipoproteins, such as oxidized LDL (51). Cluster of differentiation (CD)36 and oxidized lectin-like low-density lipoprotein receptor (LOX)-1 allow internalization of oxidized LDL, and promote conversion of macrophages to foam cells. These cells secrete various inflammatory mediators (IL-1β, IL-6, TNF-α) and chemokines (MCP-1) that stimulate expression of endothelial cell adhesion molecules and cause an ongoing leukocyte accumulation in the intima. Recruitment of additional immune cells into the intima, in particular T-lymphocytes and mast cells, contributes to the extravascular inflammatory processes. T-cells within the intima are predominantly T-helper (Th1) cells. These cells secrete cytokines, including interferon (IFN)-γ, IL-2 and TNF-α, and enhance the local inflammatory responses. Mast cells are also recruited to the site of macrophage and T-cell accumulation. These cells secrete various cytokines and chemokines, promote ongoing inflammation and contribute to the formation of foam cells by stimulating with aggregated LDL aggregation which are phagocytosed by macrophages (52–53).

With the production of inflammatory stimuli as well as migration and proliferation of vascular smooth muscle cells (VSMCs) within the intima, the plaques increase in complexity over time (54). VSMCs synthesize and secrete collagen, resulting in expansion of the extracellular matrix (ECM) and formation of a fibrous cap. Additionally, VSMCs secrete cytokines and chemokines that promote recruitment of leukocytes, increase endothelial permeability, and contribute to the expansion of atherosclerotic plaques. Cytokines also stimulate the expression of the coagulation factors such as tissue factor (TF) by macrophages, endothelial cells and VSMCs. TF acts as a potent initiator of the coagulation cascade via interaction with plasma coagulation factor VII, resulting in generation of thrombin and consequent activation of platelets and conversion of fibrinogen to fibrin . Binding of CD40 ligand (CD40L) to CD40 receptors on activated T-cells, endothelial cells, VSMCs, and macrophages that subsequently express TF. Excessive accumulation of oxidized LDL in macrophages ultimately leads to their demise and release of lipids and TF from these cells creates a necrotic plaque (55–56).


The inflammatory mediators contributing to atherosclerosis and CHD are synthesized and secreted in the vicinity of plaques and influence the disease progression.

5.1. C-reactive protein (CRP)

Low plasma level of CRP is an indicator of health while high levels is an indication of inflammation in CHD. After a cardiovascular event, CRP levels may be useful in short-term prognosis and long-term risk assessment of the disease. CRP is an annular, pentameric protein found in plasma that increases in response to inflammation. The protein binds to phosphocholine which is expressed on the surface of dying or dead cells. This interaciton activates the complement system, and promotes phagocytosis by macrophages that clear necrotic and apoptotic cells at the site of injury. CRP is mainly synthesized in the liver, but is also produced by leukocytes and adipocytes (57). This protein has been shown to be a marker of systemic inflammation, injury, infection, and other inflammatory stimuli (58). Serum level of CRP is stable in the absence inflammation, however, its level is increased by hepatocytes by IL-6 stimulation. Patients with elevated basal levels of CRP are at increased risk of diabetes, hypertension and cardiovascular disease (59).

Circulating levels of CRP increase in response to several cardiovascular risk factors, such as obesity, smoking, high blood pressure, increased heart rate, as well as serum levels of triglycerides, apolipoprotein B, fasting blood glucose, fibrinogen and high-density lipoprotein (HDL) cholesterol. In addition to its role as a powerful inflammatory marker, increasing evidence suggests that CRP participates directly in atherogenesis (60–61). Serum levels of CRP are elevated in patients with acute and chronic coronary heart disease and correlate with the plaque composition as well as in patients who suffer from complications of heart failure (62). A large-scale prospective study has documented a strong association between the predictive power of CRP and CHD risk with CRP levels being a more reliable biomarker of cardiovascular disease than LDL-cholesterol (63). However, a combination of CRP and LDL-cholesterol levels has a higher prognostic value than each factor alone.

5.2. Complement

Complement is a component of the innate immune system that with antibodies and phagocytic cells clear pathogens. By and large, the proteins of the complement system are synthesized by hepatocytes. A significant amount of complement is also produced by tissue macrophages, blood monocytes, and epithelial cells of the genitourinary and gastrointestinal tracts. Complements are activated through a classical as well as an alternate pathway. Activation of the classical complement pathway is, in general, initiated by binding of antibody to C1 (comprising C1q, C1r and C1s subunits) via the C1q subunit. This action induces a conformational change and promotes C4 cleavage by C1s. Subsequently, C2 forms C4b2b C3 convertase, which cleaves C3 to C3a and C3b. Factors B or D and properdin are proteins specific for the alternative complement cascade that give rise to C3 convertase, C5 convertase and C5b-9 (64–65). C5 convertase activates the common pathway of the complement cascade and leads to the generation of C5b-9 (“membrane attack complex”). However, the alternative pathway is continuously activated at a low level as a result of spontaneous C3 hydrolysis due to breakdown of the internal thioester bonds. Unlike other pathways, the alternative pathway does not rely on binding of antibodies to pathogens. C3b is generated from C3 by a C3 convertase enzyme complex in the fluid phase, and is inactivated rapidly by Factors H and I. C3b-like C3 is a product that is produced as a result of spontaneous cleavage of the internal thioester. In contrast, when the internal thioester of C3 reacts with a hydroxyl or amino group of a molecule on the surface of a cell or pathogen, C3b covalently binds to the surface and is protected from inactivation by factor H. Surface-bound C3b may bind factor B to form C3bB. In the presence of factor D, this complex is cleaved to Ba and Bb. Bb remains associated with C3b and forms C3bBb complex which represents the stabilized form of C3 convertase. This complex is further stabilized via binding to oligomers of factor P. C3bBbP acts enzymatically to cleave significantly more C3, some of which becomes covalently attached to the same surface as C3b. The newly bound C3b recruits more B, D and P, and amplifies the complement activation to a significant extent (66–67). Depending on the cell type, endogenous complement regulatory proteins, such as CD35, CD46, CD55 and CD59 limit the extent of the activtion of complement pathway.

Because inflammation is an integral part of pathogenesis of CDH, the complement system is integral to the development of the disease. Activated complement components are observed even in early atherosclerotic lesions, and frequently co-localize with CRP in plaques in the vicinity of modified lipoproteins (68-69). CRP is one of the activators of the classical complement cascade that interacts with C1q. Complement pathway is also activated through an alternative pathway that involves modified lipoproteins, which their effects are enhanced by CRP (70). Upon activation of the complement cascade by either pathway, various complexes and cleaved products of complement pathway promote the formation and progression of plaques. Two cleavage products of complement activation, C3a and C5a, are anaphylatoxins, and are potent mediators of inflammation and chemotaxis. C5a, in particular, is highly chemotactic for monocytes and T-lymphocytes, and promotes infiltration of monocytes into the ECM (71). C5a also stimulates leukocyte synthesis of IL-6, IL-1β and TNF-α and further enhances the inflammatory process (72). Both C3a and C5a can induce degranulation of mast cells, and progressively contribute to the destabilization of plaques. C5a has been shown to promote the synthesis of plasminogen activator inhibitor (PAI)-1 and inhibits fibrinolysis in mast cells (73). The C5b-9 complex is relatively ineffective in lysing nucleated cells but exerts several non-lytic effects, including promotion of release of cytokines and chemokines from VSMCs, further enhancing accumulation of monocytes and T-cells within the ECM. Upon plaque rupture, C5b-9 leads to exposure of cell membranes, promoting assembly of the prothrombinase complex which potentiates formation of TF-induced thrombin (74–75).

5.3. IL-6

IL-6 is a circulating cytokine that is secreted largely by activated macrophages and lymphocytes (76). The biologic activities of IL-6 are initiated upon its binding to a high-affinity receptor complex consisting of two membrane glycoproteins. The 80 kDa ligand binding receptor (IL-6R) binds IL-6 with low affinity, whereas a second 130 kDa signal-transducing component (gp130) is required for high-affinity binding of gp80-bound IL-6 (77). gp-130 does not interact with or bind free IL-6. A ~50 kDa soluble form of IL-6R is generated from proteolytic cleavage of membrane-bound IL-6R (78). Recombinant soluble IL-6R interacts with IL-6 in solution and augments the activity of IL-6 as a result of binding of the IL-6:IL-6sR complex to membrane-bound gp130. Elevated levels of IL-6 are associated with increased production of IL-6R. Binding and interaction of IL-6 with its receptors, gp130 and IL-6R proteins, leads to the formation of an activated signaling complex (79). These complexes bring together the intracellular regions of gp130 to initiate a signal transduction cascade through janus kinases (JAKs) and signal transducers and activators of transcription (STATs) (80). More recently, a soluble form of the gp130 receptor has been shown to be antagonistic in IL-6 signaling (81). However, the regulatory mechanisms of soluble receptor release and its functional significance are not yet clearly understood.

Obesity contributes to increased IL-6 levels and a proportion of circulating IL-6 is thought to be produced by subcutaneous adipose tissue in humans. Thus, serum level of IL-6 is correlated with body mass index (BMI) and is correlated with insulin resistance (82). Inflammation and production of IL-6 and other inflammatory proteins may be key contributing mechanisms to the development of obesity, diabetes and CHD (83–84). IL-6 along with other inflammatory proteins are systemic mediators of acute response to infection and inflammation (85). Apolipoprotein E (ApoE)–/– mice on a high-fat diet responded to stress by elevation of serum IL6 levels and showed an enhanced plaque formation (86). Increased IL-6 levels have also been reported in mice deficient in mast cells (87). As one of the key mediators in the inflammatory process, IL-6 may act upstream of CRP and complement components and contributes to a pro-coagulant state through upregulation of fibrinogen expression. The value of IL-6 as a predictor of CHD is limited due to its labile nature (half-life of ~5 min). However, other inflammatory predictors of CHD, such as CRP and complement C3, may act as surrogates for enhanced secretion of IL-6 (88). Clearly, IL-6 levels are elevated in systemic infection and inflammation, which may contribute to increased CRP in at-risk CHD patients.

5.4. Serum amyloid A (SAA)

SAA is a major protein produced in large quantities during the acute-phase response. Increased concentration of SAA in the blood is a marker of active inflammation. SAA activates multiple receptors, including toll-like receptors (TLRs), the scavenger receptor SR-BI, and the adenosine triphosphate receptor P2X7 (89). Recent studies have shown that SAA activates transcription factors, including the nuclear factor-kappa B (NF-κB) pathway (90). It is postulated that activation of the NF-κB pathway promotes release of pro-inflammatory factors expressed by M2 macrophages. These functional properties distinguish SAA from the well-characterized inflammatory factors, such as lipopolysaccharide and TNF-α, suggesting a role in maintaining homeostasis during inflammation. Elevated SAA were correlated with severity of CHD as assessed by angiography and increased risk of complications and has been used to predict increased risk of mortality in CHD patients (91-92). However, measurement of SAA level after myocardial infarction was not correlated with an increased risk of recurrent cardiovascular events (93).

5.5. The CD40/CD40 Ligand (CD40L) system

CD40 is a type of I transmembrane protein receptor and is a member of the TNF superfamily (94). CD40 exists as a dimer that, after binding of CD40L, is trimerized. CD40 is expressed mainly on B-cells and in other immune cells, epithelial cells, neuronal cells, fibroblasts, vascular-wall cells and platelets (95-96). CD40 is induced by pro-inflammatory stimuli, such as TNF-α and IFNs. CD40 is usually upregulated 6–12 hr after an initial stimulation, and remains on the cell surface for 24–72 hr. CD40L is shed in a truncated soluble form (sCD40L) which then binds CD40. Transmembrane CD40L on the platelet surface is cleaved into a 18kDa fragment, and provides the major source of circulating sCD40L. CD40L and sCD40L interact with CD40 in a range of cell types, leading to various inflammatory processes.

Increasing evidence suggests that the CD40-CD40L complex plays a pivotal role in the pathogenesis of atherosclerosis. In 1998, an anti-CD40L antibody was shown to markedly reduce the size and lipid content of atherosclerotic lesions (97). Subsequent studies reported significantly decreased plaque in CD40L knockout ApoE–/– mice (98). CD40L by stimulation of endothelial cells to express adhesion molecules accelerates adhesion of macrophages to these cells. Circulating level of sCD40L is an important marker for existence of cardiovascular disease, including atherosclerosis and acute coronary syndromes (99–100). sCD40L upregulates scavenger receptor type A and CD36, stimulates the levels of adipocyte enhancer-binding protein 1 and cholesterol efflux, activates NF-κB in macrophages, promotes formation of foam cells via CD40 ligation and enhances lipid deposition (56). Contribution of CD40 to the formation of foam cells has been established by disruption of binding of CD40 and CD40L with small interfering RNA or blockage of anti-CD40 antibody (56, 101).

5.6. Myeloperoxidase (MPO)

MPO is a peroxidase, which most abundant in leukocytes, induces free oxygen radicals (102). This lysosomal protein is stored in azurophilic granules of neutrophils and released into the extracellular space by degranulation. Recent studies have reported an association between elevated levels of MPO and severity of CHD (103). In patients with CHD, MPO produced by neutrophils is a marker for instability of plaques. Particularly in patients with stable and unstable angina pectoris, Yunoki et al. observed a significant inverse correlation between levels of plasma MPO and paraoxonase-1 bound to HDL (104) These findings suggest that a mismatch between pro- and anti-oxidants contributes to progression of coronary plaque instability.


Advances in our understanding of the mechanisms underlying atherosclerosis have implicated inflammation as a central contributor to the initiation and progression of this disease including CHD. Inflammatory biomarkers may have prognostic value for predicting cardiovascular risk in high risk patients. Traditional biomarkers, such as CRP, complement and IL-6 as well as MPO can be used for detection and assessment of severity of CHD. A combination of biomarkers are utilized in clinical diagnosis and in prognosis of CHD.


Drs Hongyu Li and Kai Sun are first authors. This study was supported by the Natural Science Foundation of the Inner Mongolia Autonomous Region (2013MS1172 and 2013MS0849).


1. N. D. Wong: Epidemiological studies of CHD and the evolution of preventive cardiology. Nat Rev Cardiol, 11(5), 276-89 (2014)
DOI: 10.1038/nrcardio.2014.26

2. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet, 385(9963), 117-71 (2015)
DOI: 10.1016/S0140-6736(14)61682-2

3. A. E. Moran, M. H. Forouzanfar, G. A. Roth, G. A. Mensah, M. Ezzati, C. J. Murray and M. Naghavi: Temporal trends in ischemic heart disease mortality in 21 world regions, 1980 to 2010: the Global Burden of Disease 2010 study. Circulation, 129(14), 1483-92 (2014)
DOI: 10.1161/CIRCULATIONAHA.113.004042
PMid:24573352 PMCid:PMC4181359

4. A. E. Moran, M. H. Forouzanfar, G. A. Roth, G. A. Mensah, M. Ezzati: The global burden of ischemic heart disease in 1990 and 2010: the Global Burden of Disease 2010 study. Circulation, 129(14), 1493-501 (2014)
DOI: 10.1161/CIRCULATIONAHA.113.004046
PMid:24573351 PMCid:PMC4181601

5. A. E. Moran, J. T. Oliver, M. Mirzaie, M. H. Forouzanfar, M. Chilov Assessing the Global Burden of Ischemic Heart Disease: Part 1: Methods for a Systematic Review of the Global Epidemiology of Ischemic Heart Disease in 1990 and 2010. Glob Heart, 7(4), 315-329 (2012)
DOI: 10.1016/j.gheart.2012.10.004
PMid:23682350 PMCid:PMC3652434

6. N. Oba, R. McCaffrey, P. Choonhapran, P. Chutug and S. Rueangram: Development of a community participation program for diabetes mellitus prevention in a primary care unit, Thailand. Nurs Health Sci, 13(3), 352-9 (2011)
DOI: 10.1111/j.1442-2018.2011.00627.x

7. A. Vaidya, P. K. Pokharel, S. Nagesh, P. Karki, S. Kumar and S. Majhi: Prevalence of coronary heart disease in the urban adult males of eastern Nepal: a population-based analytical cross-sectional study. Indian Heart J, 61(4), 341-7 (2009)

8. M. Grau, V. Bongard, M. Fito, J. B. Ruidavets, J. Sala, D. Taraszkiewicz: Prevalence of cardiovascular risk factors in men with stable coronary heart disease in France and Spain. Arch Cardiovasc Dis, 103(2), 80-9 (2010)
DOI: 10.1016/j.acvd.2009.11.006

9. M. C. Kontos, D. B. Diercks and J. D. Kirk: Emergency department and office-based evaluation of patients with chest pain. Mayo Clin Proc, 85(3), 284-99 (2010)
DOI: 10.4065/mcp.2009.0560
PMid:20194155 PMCid:PMC2843115

10. S. Kaukola: The diagonal ear-lobe crease, a physical sign associated with coronary heart disease. Acta Med Scand Suppl, 619, 1-49 (1978)

11. T. F. Luscher, A. von Eckardstein and B. Simic: Therapeutic targets to raise HDL in patients at risk or with coronary artery disease. Curr Vasc Pharmacol, 10(6), 720-4 (2012)
DOI: 10.2174/157016112803520972

12. P. de Araujo Goncalves, H. M. Garcia-Garcia, M. S. Carvalho, H. Dores: Diabetes as an independent predictor of high atherosclerotic burden assessed by coronary computed tomography angiography: the coronary artery disease equivalent revisited. Int J Cardiovasc Imaging, 29(5), 1105-14 (2013)
DOI: 10.1007/s10554-012-0168-4

13. Y. Li, X. M. Wang, Y. L. Liu, K. Shi, Y. F. Yang and Y. H. Guo: (Risk factors for coronary artery lesions in children with Kawasaki disease). Zhongguo Dang Dai Er Ke Za Zhi, 14(12), 938-41 (2012)

14. N. Mahalle, M. V. Kulkarni and S. S. Naik: Is hypomagnesaemia a coronary risk factor among Indians with coronary artery disease? J Cardiovasc Dis Res, 3(4), 280-6 (2012)

15. N. Koitabashi and M. Kurabayashi: Stroke and cardiovascular disease related with hypertriglyceridemia. Nihon Rinsho, 71(9), 1606-10 (2013)

16. B. G. Talayero and F. M. Sacks: The role of triglycerides in atherosclerosis. Curr Cardiol Rep, 13(6), 544-52 (2011) doi:10.1.007/s11886-011-0220-3
DOI: 10.1.007/s11886-011-0220-3

17. G. Ambrosio and I. Tritto: Interaction between the endothelium and blood cells in acute coronary syndromes. Ital Heart J, 2 Suppl 3, 43S-44S (2001)

18. S. Kinlay, A. P. Selwyn, P. Libby and P. Ganz: Inflammation, the endothelium, and the acute coronary syndromes. J Cardiovasc Pharmacol, 32 Suppl 3, S62-6 (1998)

19. A. Tuttolomondo, D. Di Raimondo, R. Pecoraro, V. Arnao, A. Pinto and G. Licata: Atherosclerosis as an inflammatory disease. Curr Pharm Des, 18(28), 4266-88 (2012)
DOI: 10.2174/138161212802481237
DOI: 10.2174/138161212802481246

20. A. Abbate, A. C. Morton and D. C. Crossman: Anti-inflammatory therapies in myocardial infarction. Lancet, 385(9987), 2573-4 (2015)
DOI: 10.1016/S0140-6736(15)61153-9

21. M. R. Bacci, J. A. Santos and L. F. Nogueira: Coronary stent stenosis in acute myocardial infarction. BMJ Case Rep, 2013 (2013)

22. N. H. Pijls: Acute myocardial infarction and underlying stenosis severity. Am J Cardiol, 103(9), 1204-5 (2009)
DOI: 10.1016/j.amjcard.2009.01.027

23. K. Tanaka and M. Sata: Atherosclerosis: progress in diagnosis and treatments. Topics: II. Atherosclerosis -promoting factors; pathogenesis and pathophysiology; 3. From basic research: focusing on large and peripheral vessels. Nihon Naika Gakkai Zasshi, 102(2), 305-12 (2013)
DOI: 10.2169/naika.102.305

24. H. Plasschaert, S. Heeneman and M. J. Daemen: Progression in atherosclerosis: histological features and pathophysiology of atherosclerotic lesions. Top Magn Reson Imaging, 20(4), 227-37 (2009)
DOI: 10.1097/RMR.0b013e3181ea2869

25. K. Sakakura, M. Nakano, F. Otsuka, E. Ladich, F. D. Kolodgie and R. Virmani: Pathophysiology of atherosclerosis plaque progression. Heart Lung Circ, 22(6), 399-411 (2013)
DOI: 10.1016/j.hlc.2013.03.001

26. D. Tousoulis, A. M. Kampoli, N. Papageorgiou, E. Androulakis, C. Antoniades: Pathophysiology of atherosclerosis: the role of inflammation. Curr Pharm Des, 17(37), 4089-110 (2011)
DOI: 10.2174/138161211798764843

27. P. Libby, P. M. Ridker and G. K. Hansson: Inflammation in atherosclerosis: from pathophysiology to practice. J Am Coll Cardiol, 54(23), 2129-38 (2009)
DOI: 10.1016/j.jacc.2009.09.009
PMid:19942084 PMCid:PMC2834169

28. A. D’Souza, M. Hussain, F. C. Howarth, N. M. Woods: Pathogenesis and pathophysiology of accelerated atherosclerosis in the diabetic heart. Mol Cell Biochem, 331(1-2), 89-116 (2009)

29. V. Mallika, B. Goswami and M. Rajappa: Atherosclerosis pathophysiology and the role of novel risk factors: a clinicobiochemical perspective. Angiology, 58(5), 513-22 (2007)
DOI: 10.1177/0003319707303443

30. M. F. Lopes-Virella and G. Virella: Pathogenic role of modified LDL antibodies and immune complexes in atherosclerosis. J Atheroscler Thromb, 20(10), 743-54 (2013)
DOI: 10.5551/jat.19281

31. I. Peluso, G. Morabito, L. Urban, F. Ioannone and M. Serafini: Oxidative stress in atherosclerosis development: the central role of LDL and oxidative burst. Endocr Metab Immune Disord Drug Targets, 12(4), 351-60 (2012)
DOI: 10.2174/187153012803832602

32. A. Hovland, K. T. Lappegard and T. E. Mollnes: LDL apheresis and inflammation--implications for atherosclerosis. Scand J Immunol, 76(3), 229-36 (2012)
DOI: 10.1111/j.1365-3083.2012.02734.x

33. R. L. Wilensky, Y. Shi, E. R. Mohler, 3rd, D. Hamamdzic, M. E. Burgert: Inhibition of lipoprotein-associated phospholipase A2 reduces complex coronary atherosclerotic plaque development. Nat Med, 14(10), 1059-66 (2008)
DOI: 10.1038/nm.1870
PMid:18806801 PMCid:PMC2885134

34. R. S. Rosenson, M. Vracar-Grabar and I. Helenowski: Lipoprotein associated phospholipase A2 inhibition reduces generation of oxidized fatty acids: Lp-LPA2 reduces oxidized fatty acids. Cardiovasc Drugs Ther, 22(1), 55-8 (2008)
DOI: 10.1007/s10557-008-6080-4

35. K. M. Patel, A. Strong, J. Tohyama, X. Jin, C. R. Morales: Macrophage sortilin promotes LDL uptake, foam cell formation, and atherosclerosis. Circ Res, 116(5), 789-96 (2015)
DOI: 10.1161/CIRCRESAHA.116.305811
PMid:25593281 PMCid:PMC4602371

36. D. Rott, J. Zhu, Y. F. Zhou, M. S. Burnett, A. Zalles-Ganley and S. E. Epstein: IL-6 is produced by splenocytes derived from CMV-infected mice in response to CMV antigens, and induces MCP-1 production by endothelial cells: a new mechanistic paradigm for infection-induced atherogenesis. Atherosclerosis, 170(2), 223-8 (2003)
DOI: 10.1016/S0021-9150(03)00295-8

37. J. Fruebis, V. Gonzalez, M. Silvestre and W. Palinski: Effect of probucol treatment on gene expression of VCAM-1, MCP-1, and M-CSF in the aortic wall of LDL receptor-deficient rabbits during early atherogenesis. Arterioscler Thromb Vasc Biol, 17(7), 1289-302 (1997)
DOI: 10.1161/01.ATV.17.7.1289

38. M. Drechsler, J. Duchene and O. Soehnlein: Chemokines control mobilization, recruitment, and fate of monocytes in atherosclerosis. Arterioscler Thromb Vasc Biol, 35(5), 1050-5 (2015)
DOI: 10.1161/ATVBAHA.114.304649

39. E. Butoi, A. M. Gan and I. Manduteanu: Molecular and functional interactions among monocytes/macrophages and smooth muscle cells and their relevance for atherosclerosis. Crit Rev Eukaryot Gene Expr, 24(4), 341-55 (2014)
DOI: 10.1615/CritRevEukaryotGeneExpr.2014012157

40. A. Roessner, A. Herrera, H. J. Honing, E. Vollmer, G. Zwadlo, R. Schurmann, C. Sorg and E. Grundmann: Identification of macrophages and smooth muscle cells with monoclonal antibodies in the human atherosclerotic plaque. Virchows Arch A Pathol Anat Histopathol, 412(2), 169-74 (1987)
DOI: 10.1007/BF00716190

41. J. F. Zhao, L. C. Ching, Y. C. Huang, C. Y. Chen, A. N. Chiang: Molecular mechanism of curcumin on the suppression of cholesterol accumulation in macrophage foam cells and atherosclerosis. Mol Nutr Food Res, 56(5), 691-701 (2012)
DOI: 10.1002/mnfr.201100735

42. Y. Yuan, P. Li and J. Ye: Lipid homeostasis and the formation of macrophage-derived foam cells in atherosclerosis. Protein Cell, 3(3), 173-81 (2012)
DOI: 10.1007/s13238-012-2025-6
PMid:22447659 PMCid:PMC4875426

43. N. R. Webb and K. J. Moore: Macrophage-derived foam cells in atherosclerosis: lessons from murine models and implications for therapy. Curr Drug Targets, 8(12), 1249-63 (2007)
DOI: 10.2174/138945007783220597

44. Z. J. Cheng, H. Vapaatalo and E. Mervaala: Angiotensin II and vascular inflammation. Med Sci Monit, 11(6), RA194-205 (2005)

45. H. S. Lim, D. Felmeden and G. Y. Lip: Angiotensin II-mediated vascular inflammation: the balance between vascular endothelial growth factor and angiopoietins. Hypertension, 45(2), e3 (2005)
DOI: 10.1161/01.HYP.0000151886.26341.4b

46. C. R. Tirapelli, D. Bonaventura, L. F. Tirapelli and A. M. de Oliveira: Mechanisms underlying the vascular actions of endothelin 1, angiotensin II and bradykinin in the rat carotid. Pharmacology, 84(2), 111-26 (2009)
DOI: 10.1159/000231974

47. S. J. Hwang, C. M. Ballantyne, A. R. Sharrett, L. C. Smith: Circulating adhesion molecules VCAM-1, ICAM-1, and E-selectin in carotid atherosclerosis and incident coronary heart disease cases: the Atherosclerosis Risk In Communities (ARIC) study. Circulation, 96(12), 4219-25 (1997)
DOI: 10.1161/01.CIR.96.12.4219

48. A. K. Stannard, R. Khurana, I. M. Evans, V. Sofra, D. I. Holmes and I. Zachary: Vascular endothelial growth factor synergistically enhances induction of E-selectin by tumor necrosis factor-alpha. Arterioscler Thromb Vasc Biol, 27(3), 494-502 (2007)
DOI: 10.1161/01.ATV.0000255309.38699.6c

49. Y. Wang, L. Wang, X. Ai, J. Zhao, X. Hao, Y. Lu and Z. Qiao: Nicotine could augment adhesion molecule expression in human endothelial cells through macrophages secreting TNF-alpha, IL-1beta. Int Immunopharmacol, 4(13), 1675-86 (2004)
DOI: 10.1016/j.intimp.2004.07.028

50. X. Zhang, X. Liu, H. Shang, Y. Xu and M. Qian: Monocyte chemoattractant protein-1 induces endothelial cell apoptosis in vitro through a p53-dependent mitochondrial pathway. Acta Biochim Biophys Sin (Shanghai), 43(10), 787-95 (2011)
DOI: 10.1093/abbs/gmr072

51. G. Virella, D. Atchley, S. Koskinen, D. Zheng and M. F. Lopes-Virella: Proatherogenic and proinflammatory properties of immune complexes prepared with purified human oxLDL antibodies and human oxLDL. Clin Immunol, 105(1), 81-92 (2002)
DOI: 10.1006/clim.2002.5269

52. I. Kriszbacher, M. Koppan and J. Bodis: Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med, 353(4), 429-30; author reply 429-30 (2005)

53. C. Weber and H. Noels: Atherosclerosis: current pathogenesis and therapeutic options. Nat Med, 17(11), 1410-22 (2011)
DOI: 10.1038/nm.2538

54. H. Li, M. I. Cybulsky, M. A. Gimbrone, Jr. and P. Libby: An atherogenic diet rapidly induces VCAM-1, a cytokine-regulatable mononuclear leukocyte adhesion molecule, in rabbit aortic endothelium. Arterioscler Thromb, 13(2), 197-204 (1993)
DOI: 10.1161/01.ATV.13.2.197

55. C. Antoniades, C. Bakogiannis, D. Tousoulis, A. S. Antonopoulos and C. Stefanadis: The CD40/CD40 ligand system: linking inflammation with atherothrombosis. J Am Coll Cardiol, 54(8), 669-77 (2009)
DOI: 10.1016/j.jacc.2009.03.076

56. M. Yuan, H. Fu, L. Ren, H. Wang and W. Guo: Soluble CD40 ligand promotes macrophage foam cell formation in the etiology of atherosclerosis. Cardiology, 131(1), 1-12 (2015)
DOI: 10.1159/000374105

57. M. B. Pepys and G. M. Hirschfield: C-reactive protein: a critical update. J Clin Invest, 111(12), 1805-12 (2003)
DOI: 10.1172/JCI200318921
PMid:12813013 PMCid:PMC161431

58. Y. Wu, L. A. Potempa, D. El Kebir and J. G. Filep: C-reactive protein and inflammation: conformational changes affect function. Biol Chem (2015)

59. L. H. Kuller, R. P. Tracy, J. Shaten and E. N. Meilahn: Relation of C-reactive protein and coronary heart disease in the MRFIT nested case-control study. Multiple Risk Factor Intervention Trial. Am J Epidemiol, 144(6), 537-47 (1996)
DOI: 10.1093/oxfordjournals.aje.a008963

60. R. Rajtar, W. Kolasinska-Kloch and M. Kloch: (C-reactive protein in patients with coronary heart disease). Folia Med Cracov, 45(1-2), 25-32 (2004)

61. G. Latkovskis, N. Licis and U. Kalnins: C-reactive protein levels and common polymorphisms of the interleukin-1 gene cluster and interleukin-6 gene in patients with coronary heart disease. Eur J Immunogenet, 31(5), 207-13 (2004)
DOI: 10.1111/j.1365-2370.2004.00476.x

62. M. Kivimaki and I. Kawachi: Regarding the relationship between the inflammatory marker C-reactive protein and coronary heart disease. Am J Epidemiol, 178(1), 154-5 (2013)
DOI: 10.1093/aje/kwt105
PMid:23980285 PMCid:PMC3698995

63. P. M. Ridker, W. Koenig and V. Fuster: C-reactive protein and coronary heart disease. N Engl J Med, 351(3), 295-8; author reply 295-8 (2004)

64. K. Sakai, M. Yasuda, K. Tomooka and M. Nobunaga: (Activation mechanism and reaction process of the complement system--the classical pathway). Nihon Rinsho, 37(5), 943-55 (1979)

65. R. R. Porter and K. B. Reid: Activation of the complement system by antibody-antigen complexes: the classical pathway. Adv Protein Chem, 33, 1-71 (1979)
DOI: 10.1016/S0065-3233(08)60458-1

66. C. Bentley, W. Fries and V. Brade: Synthesis of factors D, B and P of the alternative pathway of complement activation, as well as of C3, by guinea-pig peritoneal macrophages in vitro. Immunology, 35(6), 971-80 (1978)

67. T. Fujita: Activation pathway of complement (classical, alternative, lectin). Nihon Rinsho, 63 Suppl 4, 269-73 (2005)

68. K. Yasojima, C. Schwab, E. G. McGeer and P. L. McGeer: Complement components, but not complement inhibitors, are upregulated in atherosclerotic plaques. Arterioscler Thromb Vasc Biol, 21(7), 1214-9 (2001)
DOI: 10.1161/hq0701.092160

69. K. Yasojima, C. Schwab, E. G. McGeer and P. L. McGeer: Generation of C-reactive protein and complement components in atherosclerotic plaques. Am J Pathol, 158(3), 1039-51 (2001)
DOI: 10.1016/S0002-9440(10)64051-5

70. J. E. Volanakis and M. H. Kaplan: Interaction of C-reactive protein complexes with the complement system. II. Consumption of guinea pig complement by CRP complexes: requirement for human C1q. J Immunol, 113(1), 9-17 (1974)

71. S. R. Marder, D. E. Chenoweth, I. M. Goldstein and H. D. Perez: Chemotactic responses of human peripheral blood monocytes to the complement-derived peptides C5a and C5a des Arg. J Immunol, 134(5), 3325-31 (1985)

72. S. O’Barr and N. R. Cooper: The C5a complement activation peptide increases IL-1beta and IL-6 release from amyloid-beta primed human monocytes: implications for Alzheimer’s disease. J Neuroimmunol, 109(2), 87-94 (2000)
DOI: 10.1016/S0165-5728(00)00291-5

73. H. Ali: Regulation of human mast cell and basophil function by anaphylatoxins C3a and C5a. Immunol Lett, 128(1), 36-45 (2010)
DOI: 10.1016/j.imlet.2009.10.007
PMid:19895849 PMCid:PMC2815128

74. H. G. Rus, F. Niculescu, E. Constantinescu, A. Cristea and R. Vlaicu: Immunoelectron-microscopic localization of the terminal C5b-9 complement complex in human atherosclerotic fibrous plaque. Atherosclerosis, 61(1), 35-42 (1986)
DOI: 10.1016/0021-9150(86)90111-5

75. R. Vlaicu, F. Niculescu, H. G. Rus and A. Cristea: Immunohistochemical localization of the terminal C5b-9 complement complex in human aortic fibrous plaque. Atherosclerosis, 57(2-3), 163-77 (1985)

76. J. Mauer, J. L. Denson and J. C. Bruning: Versatile functions for IL-6 in metabolism and cancer. Trends Immunol, 36(2), 92-101 (2015)
DOI: 10.1016/j.it.2014.12.008

77. T. Taga, M. Hibi, Y. Hirata, K. Yamasaki, K. Yasukawa, T. Matsuda, T. Hirano and T. Kishimoto: Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130. Cell, 58(3), 573-81 (1989)
DOI: 10.1016/0092-8674(89)90438-8

78. T. Kubota and A. Yokoyama: Interleukin-6 (IL-6)/soluble IL-6 receptor(sIL-6R). Nihon Rinsho, 68 Suppl 7, 75-7 (2010)

79. M. Kaneda, T. Odaka, H. Suetake, D. Tahara and T. Miyadai: Teleost IL-6 promotes antibody production through STAT3 signaling via IL-6R and gp130. Dev Comp Immunol, 38(2), 224-31 (2012)
DOI: 10.1016/j.dci.2012.02.002

80. F. Legendre, J. Dudhia, J. P. Pujol and P. Bogdanowicz: JAK/STAT but not ERK1/ERK2 pathway mediates interleukin (IL)-6/soluble IL-6R down-regulation of Type II collagen, aggrecan core, and link protein transcription in articular chondrocytes. Association with a down-regulation of SOX9 expression. J Biol Chem, 278(5), 2903-12 (2003)
DOI: 10.1074/jbc.M110773200

81. K. Murakami-Mori, T. Taga, T. Kishimoto and S. Nakamura: The soluble form of the IL-6 receptor (sIL-6R alpha) is a potent growth factor for AIDS-associated Kaposi’s sarcoma (KS) cells; the soluble form of gp130 is antagonistic for sIL-6R alpha-induced AIDS-KS cell growth. Int Immunol, 8(4), 595-602 (1996)
DOI: 10.1093/intimm/8.4.595

82. J. Mauer, B. Chaurasia, J. Goldau, M. C. Vogt, J. Ruud, K. D. Nguyen: Signaling by IL-6 promotes alternative activation of macrophages to limit endotoxemia and obesity-associated resistance to insulin. Nat Immunol, 15(5), 423-30 (2014)
DOI: 10.1038/ni.2865
PMid:24681566 PMCid:PMC4161471

83. G. B. Lim: Coronary artery disease: IL-6 signaling linked with CHD. Nat Rev Cardiol, 9(6), 313 (2012)
DOI: 10.1038/nrcardio.2012.46

84. X. W. Jia, Y. P. Tian, Y. Wang, X. X. Deng and Z. N. Dong: Correlation of polymorphism in IL-6 gene promoter with BMI, inflammatory factors, and pathogenesis and progression of CHD. Zhongguo Shi Yan Xue Ye Xue Za Zhi, 15(6), 1270-5 (2007)

85. K. M. Beavers, D. P. Beavers, J. J. Newman, A. M. Andersonr: Effects of total and regional fat loss on plasma CRP and IL-6 in overweight and obese, older adults with knee osteoarthritis. Osteoarthritis Cartilage, 23(2), 249-56 (2015)
DOI: 10.1016/j.joca.2014.11.005
PMid:25450847 PMCid:PMC4304884

86. E. Bernberg, M. A. Ulleryd, M. E. Johansson and G. M. Bergstrom: Social disruption stress increases IL-6 levels and accelerates atherosclerosis in ApoE-/- mice. Atherosclerosis, 221(2), 359-65 (2012)
DOI: 10.1016/j.atherosclerosis.2011.11.041

87. K. Ganeshan and P. J. Bryce: Regulatory T cells enhance mast cell production of IL-6 via surface-bound TGF-beta. J Immunol, 188(2), 594-603 (2012)
DOI: 10.4049/jimmunol.1102389
PMid:22156492 PMCid:PMC3253181

88. J. M. Stapp, V. Sjoelund, H. A. Lassiter, R. C. Feldhoff and P. W. Feldhoff: Recombinant rat IL-1beta and IL-6 synergistically enhance C3 mRNA levels and complement component C3 secretion by H-35 rat hepatoma cells. Cytokine, 30(2), 78-85 (2005)
DOI: 10.1016/j.cyto.2004.12.007

89. R. D. Ye and L. Sun: Emerging functions of serum amyloid A in inflammation. J Leukoc Biol (2015)

90. Y. Lv, X. Zhang, Y. Sun and S. Zhang: Activation of NF-kappaB contributes to production of pig-major acute protein and serum amyloid A in pigs experimentally infected with porcine circovirus type 2. Res Vet Sci, 95(3), 1235-40 (2013)
DOI: 10.1016/j.rvsc.2013.08.006

91. J. R. Delanghe, M. R. Langlois, D. De Bacquer, R. Mak, P. Capel, L. Van Renterghem and G. De Backer: Discriminative value of serum amyloid A and other acute-phase proteins for coronary heart disease. Atherosclerosis, 160(2), 471-6 (2002)
DOI: 10.1016/S0021-9150(01)00607-4

92. B. D. Johnson, K. E. Kip, O. C. Marroquin, P. M. Ridker: Serum amyloid A as a predictor of coronary artery disease and cardiovascular outcome in women: the National Heart, Lung, and Blood Institute-Sponsored Women’s Ischemia Syndrome Evaluation (WISE). Circulation, 109(6), 726-32 (2004)
DOI: 10.1161/01.CIR.0000115516.54550.B1

93. T. S. Harb, W. Zareba, A. J. Moss, P. M. Ridker, V. J. Marder, N. Rifai: Association of C-reactive protein and serum amyloid A with recurrent coronary events in stable patients after healing of acute myocardial infarction. Am J Cardiol, 89(2), 216-21 (2002)
DOI: 10.1016/S0002-9149(01)02204-4

94. S. X. Anand, J. F. Viles-Gonzalez, J. J. Badimon, E. Cavusoglu and J. D. Marmur: Membrane-associated CD40L and sCD40L in atherothrombotic disease. Thromb Haemost, 90(3), 377-84 (2003)
DOI: 10.1160/TH03-05-0268

95. U. Schonbeck and P. Libby: The CD40/CD154 receptor/ligand dyad. Cell Mol Life Sci, 58(1), 4-43 (2001)
DOI: 10.1007/PL00000776

96. R. J. Armitage, W. C. Fanslow, L. Strockbine, T. A. Sato.: Molecular and biological characterization of a murine ligand for CD40. Nature, 357(6373), 80-2 (1992)
DOI: 10.1038/357080a0

97. F. Mach, U. Schonbeck, G. K. Sukhova, E. Atkinson and P. Libby: Reduction of atherosclerosis in mice by inhibition of CD40 signalling. Nature, 394(6689), 200-3 (1998)
DOI: 10.1038/28204

98. S. Hoving, S. Heeneman, M. J. Gijbels, J. A. te Poele, J. F. Pol, K. Gabriels: Anti-inflammatory and anti-thrombotic intervention strategies using atorvastatin, clopidogrel and knock-down of CD40L do not modify radiation-induced atherosclerosis in ApoE null mice. Radiother Oncol, 101(1), 100-8 (2011)
DOI: 10.1016/j.radonc.2011.09.019

99. I. Erturan, B. K. Koroglu, A. Adiloglu, A. M. Ceyhan: Evaluation of serum sCD40L and homocysteine levels with subclinical atherosclerosis indicators in patients with psoriasis: a pilot study. Int J Dermatol, 53(4), 503-9 (2014)
DOI: 10.1111/ijd.12397

100. B. L. Xu, C. H. Bei, R. Wang and X. X. Lei: Serum sCD40L detection for risk evaluation of acute coronary syndromes. Nan Fang Yi Ke Da Xue Xue Bao, 26(11), 1656-7 (2006)

101. B. Pamukcu, G. Y. Lip, V. Snezhitskiy and E. Shantsila: The CD40-CD40L system in cardiovascular disease. Ann Med, 43(5), 331-40 (2011)
DOI: 10.3109/07853890.2010.546362

102. N. Sato, K. Kashima, Y. Tanaka, H. Shimizu and M. Mori: Effect of granulocyte-colony stimulating factor on generation of oxygen-derived free radicals and myeloperoxidase activity in neutrophils from poorly controlled NIDDM patients. Diabetes, 46(1), 133-7 (1997)
DOI: 10.2337/diab.46.1.133
DOI: 10.2337/diabetes.46.1.133

103. C. Liu, G. Xie, W. Huang, Y. Yang, P. Li and Z. Tu: Elevated serum myeloperoxidase activities are significantly associated with the prevalence of ACS and High LDL-C levels in CHD patients. J Atheroscler Thromb, 19(5), 435-43 (2012)
DOI: 10.5551/jat.9704

104. K. Yunoki, T. Naruko, M. Inaba, T. Inoue, M. Nakagawa, K. Sugioka. Becker and M. Ueda: Gender-specific correlation between plasma myeloperoxidase levels and serum high-density lipoprotein-associated paraoxonase-1 levels in patients with stable and unstable coronary artery disease. Atherosclerosis, 231(2), 308-14 (2013)
DOI: 10.1016/j.atherosclerosis.2013.08.037

Abbreviations: ApoE, apolipoprotein E; BMI, body mass index; CD40L, CD40 ligand; CHD, coronary heart disease; CRP, C-reactive protein; ECM, extracellular matrix; ICAM-1, intercellular adhesion molecule 1; IFN-γ, interferon-gamma; IL, interleukin; JAKs, janus kinases; LDL, low-density lipoprotein; MCP-1, monocyte chemoattractant protein-1; M-CSF, macrophage colony-stimulating factor; MPO, myeloperoxidase; NF-κB, nuclear factor-kappa B; NO, nitric oxide; SAA, serum amyloid A; STATs, signal transducers and activators of transcription; TF, tissue factor; TLRs, toll-like receptors; TNF-α, tumor necrosis factor-α; VCAM-1, vascular cell adhesion molecule-1; VSMCs, vascular smooth muscle cells

Key Words: Coronary heart disease, atherosclerosis, inflammation, C-reactive protein, review

Send correspondence to: Ruiping Zhao, Department of Cardiology, Baotou Central Hospital, Inner Mongolia, Baotou 014040, China, Tel.: 86 13604722558, Fax: 86-0472-6955063, E-mail: ruiping_zhao@yahoo.com