The arteriosclerotic lesion is characterized by smooth muscle cell (SMC) hyperplasia or hypertrophy and matrix protein accumulations in the intima and/or media with or without lipid deposition, resulting in thickening and stiffness of the arterial wall. Spontaneous atherosclerotic lesions are defined by arterial intimal cell proliferation, lipid accumulation, and connective tissue deposition. Arteriosclerosis includes hypertension-related arteriosclerosis, transplant atherosclerosis, restenosis after percutaneous transluminal coronary angioplasty, vein graft arteriosclerosis and (spontaneous) atherosclerosis. In vivo, vessel walls are exposed to two main hemodynamic forces: shear stress, the dragging frictional force created by blood flow, and mechanical stretch, or tension, a cyclic strain stress created by blood pressure.For instance, factors ranging from physical exertion to psychological stress lead to a transient rise in blood pressure, and if the factors are persistent and chronic, the arteriole walls gradually thicken, resulting in hypertension.
The arterial wall is composed of a highly ordered structure of cells and extracellular matrix (ECM). In the intimal layer, endothelial cells sit upon a basement membrane rich in laminin, fibronectin and type IV collagen. In the media, individual smooth muscle cells (SMCs) are surrounded by a basement membrane, and are in turn embedded in fibrillar types I, III and V collagen, type XVIII collagen, fibronectin and proteoglycans. In elastic arteries, each layer of SMCs is separated by a well-defined, fenestrated elastic lamina. The outermost layer, the adventitia, is rich in fibroblasts, collagen types I and III and elastin. So collagens are very important for blood vessel structure and play the diverse roles in atherosclerosis such as the upregulation of the infiltration and differentiation of smooth muscle cells and macrophages and the control of matrix remodeling through feedback signaling to proteinases. Collagens are important regulators of CVC-mediated calcification. Vascular calcification is an active cell-driven process which may be orchestrated by differentiated intimal cells (SMCs or macrophages) or undifferentiated progenitor cells. Intimal calcification is believed to affect plaque mechanics and susceptibility to rupture.
Advanced glycation endproducts (AGEs) are a group of modified molecular species formed by nonenzymatic reactions between the aldehydic group of reducing sugars with proteins, lipids, or nucleic acids. AGES promote vascular damage and acceleration of atherosclerotic plaque progression mainly through two mechanisms: directly, altering the functional properties of vessel wall extracellular matrix molecules, or indirectly, through activation of cell receptor-dependent signaling.