[Frontiers in Bioscience S1, 391-405, June 1, 2009]

Chemokines and cardiac fibrosis

Marcin Dobaczewski1, Nikolaos Georgios Frangogiannis1

1Section of Cardiovascular Sciences, Baylor College of Medicine, One Baylor Plaza BCM620, Houston TX 77030 USA

TABLE OF CONTENTS

1. Abstract
2. Cardiac fibrosis
3. The extracellular matrix network in the normal heart
4. The functional consequences of cardiac fibrosis
5. Inflammation and cardiac fibrosis
6. The Chemokine superfamily
7. Chemokines and tissue fibrosis
8. Chemokines and reparative fibrosis following myocardial infarction
9. The role of the CC chemokines in healing myocardial infarction
10. How does MCP-1 modulate reparative fibrosis following myocardial infarction?
11. The role of other members of the CC chemokine family in myocardial infarction.
12. CXC chemokines and reparative fibrosis following myocardial infarction.
13. The role of the chemokines in cardiac fibrosis in the absence of myocardial infarction.
14. MCP-1 is involved in the pathogenesis of experimental ischemic cardiomyopathy.
15. MCP-1 expression in patients with ischemic fibrotic cardiomyopathy.
16. The role of MCP-1 in cardiac fibrosis due to pressure and volume overload.
17. Chemokines, TGF-beta, and the transition from inflammation to fibrosis.
18. Conclusions.
19. Acknowledgment
20. References

1. ABSTRACT

Several members of the chemokine family play an important role in reparative fibrosis and are involved in the pathogenesis of remodeling following myocardial infarction. Chemokines may regulate the fibrotic process through recruitment and activation of mononuclear cell subsets and fibroblast progenitors (fibrocytes), by exerting direct effects on resident fibroblasts, and by modulating angiogenesis. Monocyte Chemoattractant Protein (MCP)-1/CCL2 is the best studied chemokine in cardiac fibrosis. Disruption of the MCP-1 axis reduces fibrosis attenuating dilation of the infarcted ventricle. In addition, MCP-1 signaling is activated in response to insults that do not cause cardiomyocyte death, such as brief ischemia or pressure overload and regulates fibrous tissue deposition in experimental models of fibrotic non-infarctive cardiomyopathy. Understanding the role of chemokine-mediated interactions in the development of cardiac fibrosis may identify novel therapeutic targets for treatment of patients with heart failure.