Inflammatory Mechanisms in Atherosclerosis: The Impact of Matrix Metalloproteinases

Author(s): Gerasimos Siasos, Dimitris Tousoulis, Stamatios Kioufis, Evangelos Oikonomou, Zoi Siasou, Maria Limperi, Athanasios G. Papavassiliou, Christodoulos Stefanadis.

Journal Name:Current Topics in Medicinal Chemistry

Volume 12 , Issue 10 , 2012

Abstract:

Inflammatory process is essential for the initiation and progression of vascular remodeling, entailing degradation and reorganization of the extra-cellular matrix (ECM) scaffold of the vessel wall, leading to the development of atherosclerotic lesions. Matrix metalloproteinases (MMPs) are zing dependent endo-peptidases found in most living organisms and act mainly by degrading ECM components. Most MMPs are formed as inactive proenzymes and are activated by proteolysis. This process depends and is regulated by other proteases and endogenous MMP inhibitors (TIMPs). MMPs and TIMPs play a major role not only in ECM degradation but also in mediating cell migration, proliferation, tissue remodeling; acting as a signal for the production and secretion of growth factors and cytokines. More importantly MMPs through proteolysis and degradation of ECM contribute in many physiological and pathological processes including organ development, wound healing, tissue support, vascular remodeling and restenosis, atherosclerosis progression, acute coronary syndromes, myocardial infarction, cardiomyopathy, aneurysms remodeling, cancer, arthritis, and chronic inflammatory diseases. A substantial body of evidence support the notion that imbalance between the activity of MMPs and their tissue inhibitors (TIMPs) contribute to the pathogenesis of cardiovascular diseases such as atherosclerosis, vascular remodeling and progression of heart failure. In this review, we will discuss the relationship between MMPs, inflammation and atherosclerosis under the topic of cardiovascular disease.

Keywords: Atherosclerosis, cardiac remodeling, cardiovascular risk factors, endothelial function, extra-cellular matrix, cell migration, inflammation, atherosclerosis progression, matrix metalloproteinases, cardiovascular disease. vascular remodeling, atherosclerotic lesion, cell surface proteins, chronic inflammatory diseases

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Article Details

VOLUME: 12
ISSUE: 10
Year: 2012
Page: [1132 - 1148]
Pages: 17
DOI: 10.2174/1568026611208011132
Price: $58