[Frontiers in Bioscience S2, 194-208, January 1, 2010]

Pathophysiology of the proatherothrombotic state in the metabolic syndrome

Ivan Palomo1, Rodrigo Moore-Carrasco1, Marcelo Alarcon1, Armando Rojas2, Francisco Espana3, Vicente Andres4, Herminia Gonzalez-Navarro4

1Research Program of Cardiovascular Disease Risk, Department of Clinical Biochemistry and Immunohematology, Faculty of Health Sciences, Universidad de Talca, Chile, 2Biomedical Research Laboratory, School of Medicine, Universidad Catolica del Maule, Chile, 3Research Center, Hospital Universitario La Fe, Valencia, Spain, 4Laboratory of Vascular Biology, Department of Molecular and Cellular Pathology and Therapy, Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Cientificas, Valencia, Spain

TABLE OF CONTENTS

1. Abstract
2. Pathophysiology of the metabolic syndrome
3. Endothelial dysfunction in the metabolic syndrome
3.1. Evidence of endothelial dysfunction in the metabolic syndrome and underlying mechanisms
3.2. Mouse models of endothelial dysfunction based on nitric oxide synthase-deficiency
4. Alterations in plaque stability, coagulation and fibrinolysis systems in the metabolic syndrome
4.1. Hypercoagulation and hypofibrinolysis states
4.2. Platelet activation
5. Mouse models to study plaque vulnerability and thrombus formation
6. Mouse models of atherothrombosis and metabolic syndrome
7. Conclusions and perspectives
8. Acknowledgements
9. References

1. ABSTRACT

Obesity and insulin resistance are very frequently associated to the metabolic syndrome (MetS), play a pivotal role in the development of type 2 diabetes mellitus (T2DM) and increases the risk of cardiovascular disease. Although it varies among ethnic groups, the worldwide prevalence of MetS is 23% in young adults and increases with age. Remarkably, the prevalence of MetS is expected to rise during the next decades due to the acquisition of unhealthy life-style habits (sedentarism, smoking, unhealthy diet). A major pathological alteration present in the MetS is a prothrombotic state resulting from endothelial dysfunction and hypercoagulability produced by a dysbalance of coagulation factors and proteins regulating fibrinolysis. Although intensive research in recent years has identified a number of prothrombotic alterations in MetS patients, a better understanding of the molecular mechanisms underlying the relationship between MetS and atherotrombosis is required to improve prevention and treatment. In this review we discuss the main alterations in the endothelial function, coagulation cascade, fibrinolysis and platelet function promoting atherothrombosis in MetS and available mouse models exhibiting alterations in atherothrombosis.