Increased TNF-a, IL-6, PAI-1, leptin, and resistin, and decreased adiponectin promote insulin resistance, leading to impaired glucose management and diabetes. Some of these adipokines also affect endothelial function and the coagulation system, promoting atherosclerosis. The low-grade inflammatory state created by abnormal adipokine levels is likely an important connection between metabolic syndrome and cardiovascular disease.
Adipokines play several roles in the atherosclerotic inflammatory process:
- TNF-a activity produces inflammatory changes in vascular tissue and adhesion molecules. This increases the ability of monocytes to adhere to vessel walls.
- Resistin also promotes cell adhesion.
- Angiotensin II from angiotensinogen enhances the adhesion process of monocytes and platelets to vessel walls.
- When glucose levels are increased, leptin assists in the incorporation of lipids by enhancing uptake of cholesterol by macrophages.
- IL-6 enhances the inflammatory process and increases CRP.
- If there are ruptured atherosclerotic plaques, PAI-1 increases probability of thrombus formation and inhibits fibrin clot lysis.