BACKGROUND: In contrast to the well-known morphologic lesions of arteriosclerosis, the initial changes of the disease are less obvious. Commonly, functional disturbances of the endothelium, endothelial dysfunction, are suggested. On the other hand the significance of age-dependent changes in the extracellular matrix with their important role in vessel wall permeability and other features associated with arteriosclerosis should not be overlooked. New topics deal with possible infectious factors, the genetic basis of the disease and the particularities of the unstable atheroma. OBJECTIVE: Alterations in nitric monoxide and endothelin-1 balance of the endothelium are the key events in the initiation of arteriosclerosis induced by oxidized lipoproteins, cigarette smoking and endotoxin. This frequently supposed mechanism contrasts with earlier opinions on the primary alterations in glycosaminoglycan metabolism and other components of the extracellular matrix against atherogenic factors like hypertension, stress and physical inactivity. Based on a survey of the literature and our own experimental experiences, these changes in connection with the morphometrically determined age-conditioned increase in vascular wall thickness and the above-mentioned new topics on arteriosclerosis were analyzed. CONCLUSION: The initial lesions of arteriosclerosis starting in youth seem to be fundamentally different from those beginning in old age. The first step in the development of fatty streaks in the arteries of young people is endothelial dysfunction with a decreased formation of nitric monoxide and an increased expression of adhesion molecules. In comparison the genesis of arteriosclerosis in advanced age is characterized by metabolic changes in the endothelium combined with age-conditioned alterations in the extracellular matrix resulting in faster progression of the disease in old age. The multicausal genesis of arteriosclerosis cannot be doubted even if cooperation with infectious factors cannot be excluded. The histopathologic peculiarities of unstable atheroma are described. Copyright 2000 S. Karger AG, Basel
BACKGROUND: In contrast to the well-known morphologic lesions of arteriosclerosis, the initial changes of the disease are less obvious. Commonly, functional disturbances of the endothelium, endothelial dysfunction, are suggested. On the other hand the significance of age-dependent changes in the extracellular matrix with their important role in vessel wall permeability and other features associated with arteriosclerosis should not be overlooked. New topics deal with possible infectious factors, the genetic basis of the disease and the particularities of the unstable atheroma. OBJECTIVE: Alterations in nitric monoxide and endothelin-1 balance of the endothelium are the key events in the initiation of arteriosclerosis induced by oxidized lipoproteins, cigarette smoking and endotoxin. This frequently supposed mechanism contrasts with earlier opinions on the primary alterations in glycosaminoglycan metabolism and other components of the extracellular matrix against atherogenic factors like hypertension, stress and physical inactivity. Based on a survey of the literature and our own experimental experiences, these changes in connection with the morphometrically determined age-conditioned increase in vascular wall thickness and the above-mentioned new topics on arteriosclerosis were analyzed. CONCLUSION: The initial lesions of arteriosclerosis starting in youth seem to be fundamentally different from those beginning in old age. The first step in the development of fatty streaks in the arteries of young people is endothelial dysfunction with a decreased formation of nitric monoxide and an increased expression of adhesion molecules. In comparison the genesis of arteriosclerosis in advanced age is characterized by metabolic changes in the endothelium combined with age-conditioned alterations in the extracellular matrix resulting in faster progression of the disease in old age. The multicausal genesis of arteriosclerosis cannot be doubted even if cooperation with infectious factors cannot be excluded. The histopathologic peculiarities of unstable atheroma are described. Copyright 2000 S. Karger AG, Basel
Authors: Jason D Allen; Thomas Stabler; Aarti Kenjale; Katherine L Ham; Jennifer L Robbins; Brian D Duscha; Devon A Dobrosielski; Brian H Annex Journal: Free Radic Biol Med Date: 2010-07-08 Impact factor: 7.376
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