| pubmed-article:17653215 | pubmed:abstractText | Extracellular matrix (ECM) remodeling with successive tissue fibrosis is a key feature of chronic cardiovascular diseases, including atherosclerosis and restenosis. The atherogenic changes underlying these pathologies result from chronification of an acute repair response towards injurious and inflammatory stimuli. Thereby functional tissue is replaced by excessive ECM deposition. In the kidney, impaired remodeling is a major cause of perivascular, interstitial, and glomerular fibrosis but also a common complication of chronic hypertension. Experimental evidence points to the matrix metalloproteases (MMPs) and their intrinsic inhibitors, the tissue inhibitors of MMPs as key mediators of atherogenic and fibrotic pathologies. Mechanistically, a deregulation in ECM turnover tightly correlates with an increased production and release of proinflammatory and profibrotic factors including interleukin-1beta, transforming growth factor beta, angiotensin II, and reactive oxygen species. Unlike these factors the pleiotropic messenger molecule nitric oxide (NO) by acting as the major physiological vasodilator has emerged as one of the most atheroprotective factors. However, under inflammatory conditions NO does acquire proatherogenic and profibrotic properties thereby exacerbating tissue fibrosis. In this review, the mechanisms underlying both opposing properties of NO on perivascular ECM remodeling will exemplarily be discussed for renal fibrosis with a particular focus on the MMPs and intrinsic protease inhibitors. | lld:pubmed |
