Vascular fibrosis in atherosclerosis

Vascular fibrosis, characterized by reduced lumen diameter and arterial wall thickening attributable to excessive deposition of extracellular matrix (ECM), links with many clinical diseases and pathological progresses including atherosclerosis. It involves proliferation of vascular smooth muscle cell (VSMC), accumulation of ECM and inhibition of matrix degradation. The risk factors associated with cardiovascular disease, including hypertension, hyperglycemia, dyslipidemia and hyperhomocysteinemia (HHcy), are also suggested as initiation and progression factors of vascular fibrosis. Vascular fibrosis has been found to relate to renin-angiotensin-aldosterone system (RAAS), oxidative stress, inflammatory factors, growth factors and imbalance of endothelium-derived cytokine secretion. Angiotensin II (Ang II) and aldosterone, the circulating effector hormones of RAAS, are recognized as responsible for the pathophysiology of vascular fibrosis. Transforming growth factor-beta (TGF-beta) plays a critical role in ECM accumulation and vascular remodeling via up-regulating the production of several agents including connective tissue growth factor (CTGF) and fibroblast growth factor. An imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) results in collagen accumulation and adverse matrix remodeling. Aberrant expression or function of peroxisome proliferator-activated receptor gamma (PPAR gamma) is also associated with, and very likely contributes to, the progression of pathological fibrosis and vascular remodeling. In this review, we discuss the pathogenesis of vascular fibrosis in atherosclerosis with focus on the networking among main responsible mediators. The main pathophysiologic factors leading to vascular fibrosis will also be discussed.