Atherosclerosis extracellular matrix

These cells, located in the medial layer of the vessel wall, are normally relatively nonproliferative, but they secrete proteins which make up the extracellular matrix of the vessel wall. However, the narrowing of the arteries, a critical, often fatal, consequence of atherosclerosis is due to proliferation of VSMC and their migration into the intimal layer of the vessel wall. 

Sterol carrier protein 2 has also been shown to be involved in the intracellular transport and metabolism of cholesterol. Hirai et al. (1994) suggested that sterol carrier protein 2 plays an important role during foam cell formation induced by acetylated LDL and may be an important step in atherosclerosis [142], Lipoproteins can bind lipopolysaccharide and decrease the lipopoly-saccharide-stimulated production of proinflammatory cytokines [142, 143], In addition, lipoprotein entrapment by the extracellular matrix can lead to the progressive oxidation of LDL because of the action of lipoxygenases, reactive oxygen species, peroxynitrite, or myeloperoxidase [144, 145],... 

In the presence of specific stimuh, exemplified by cytokines and growth factors, MMPs can be up-regulated. Chronic activation of MMPs, due to an imbalance between the activity of MMPs and TIMPs, can result in excessive degradation of the extracellular matrix and is believed to contribute to the pathogenesis of several diseases, such as rheumatoid arthritis, osteoarthritis, periodontal disease, emphysema, atherosclerosis, skin ulceration, and cancer. 

Frequently called cholesterol-dependent clogging of the arteries, atherosclerosis is characterized by the progressive deposition of lipids, cells, and extracellular matrix material in the inner layer of the wall of an artery. The resulting distortion of the artery s wall can lead, either alone or in combination with a blood clot, to major blockage of blood flow. Thus, to understand the cellular basis of atherosclerosis, we need to first briefly consider the structure of an artery. ... 

Atherosclerosis is the progressive accumulation of cholesterol, inflammatoiy and other cells, and extracellular matrix in the subendothelial space (intima) of an artery wall, ultimately leading to the formation of a plaque that can occlude the lumen (see Figure 18-19). 

Slomp J, Van Munsteren JC, Poelmann RE, DeReeder EG, Bogers AJJC, Gittenber-ger-de Groot A (1992) Formation of intimal cushions in the ductus arteriosus as a model for vascular intimal thickening an immunohistochemical study of changes in the extracellular matrix components. Atherosclerosis 93 25-39... 

There has been a long-standing interest in the role of MMPs in cardiovascular disease (D2). Numerous studies have demonstrated increased levels of MMPs, especially MMP-9, at sites of atherosclerosis and aneurysms (G3, V2). The current opinion that the inflammatory process may play a leading role in the development of vascular atherosclerotic plaques has led to the suggestion that secretion and activation of MMPs by macrophages induces degradation of extracellular matrix in the atherosclerotic plaque leading to plaque rupture. Based on these concepts, MMPs have been proposed to represent sensitive markers of inflammation in patients with coronary artery disease. 

Extracellular matrix mimicry stress—strain behavior and compliance Rather than focusing on texture, one other approach arms to have similar mechanical properties to those of ECM and seems to be crucial in the cell differentiation process, especially since tissues are composed of smooth muscle cells that contract or relax depending on chemical stimuli. It has been observed that loose of vascular tissue contractility leads first to dilated vessels wall, secondly to endothelial cell dysfunction, and finally to atherosclerosis with free lumen dramatic decrease. Consequently, one assumption is to believe that newly formed tissue viability cannot be reached if mechanical properties of the fibrous scaffold do not mimic those of native tissue and particularly the native vascular wall compliance. 

The extracellular matrix of vascular wall cells, a complex array of collagen, elastin, adhesion proteins, and proteoglycans (see Chapter 13), mediates a variety of functions with significance for the development of atherosclerosis and cardiovascular disease. These include blood cell adhesion, lipoprotein binding, vascular wall... 

Abdominal aortic aneurysms represent potentially life-threatening conditions that occur in up to 10% of the aged populations in industrialized nations. An aneurysm is broadly defined as a permanent localized dilatation of an artery. AAAs arise because of substantial remodeling of the extracellular matrix and are frequently accompanied by atherosclerosis. They may be manifested by catastrophic rupture, signs of pressure on other viscera, or an embolism originating in the aneurysm wall, but most are asymptomatic. 

Wight T, The vascular extracellular matrix. In Atherosclerosis and Coronary Heart Disease, Fuster V, Ross R and Topol E, Editors. 1996, Lippincott-Raven Philadelphia, pp. 421-440. 

Wight TN. The extracellular matrix and atherosclerosis. Curr Opin Lipidol 6 326 34, 1995. 

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