Robert L
Laboratoire de Biologie Cellulaire, Paris.
C R Seances Soc Biol Fil. 1995;189(6):959-66.
A distinction is made between atheromatous plaque formation and arteriosclerosis, only this second process is strictly age-dependent. Interactions between lipids and constituents of the vascular wall are however involved in both processes, although by different mechanisms. The progressive increase with age of elastase activity is a second important factor in the age-dependent progression of arteriosclerosis. The fragmentation of elastic fibers produces elastin peptides, present in the circulating blood in microgram/ml conc-s, increasing in several arteriopathies. The constant presence of elastin peptides in the circulation maintains activated the elastin receptor (16) on endothelial cells producing NO* with vasorelaxing activity (18). The simultaneous production of superoxyde leads to the formation of peroxynitrate, neutralized by reduced glutathion. This process, maintained over decades may well impair the antiradical defense mechanisms of the cells and deprive the endothelium from the vasorelaxing activity of NO*. We propose therefore that the maintained activation of the elastin receptor with free radical and lytic enzyme production might well represent the initiating process underlying atherogenesis.
动脉粥样硬化斑块形成与动脉硬化有所区别,只有第二个过程严格依赖年龄。然而,脂质与血管壁成分之间的相互作用在这两个过程中都有涉及,尽管机制不同。弹性蛋白酶活性随年龄的逐渐增加是动脉硬化年龄依赖性进展的第二个重要因素。弹性纤维的断裂产生弹性蛋白肽,以微克/毫升的浓度存在于循环血液中,在几种动脉病变中会增加。循环中持续存在的弹性蛋白肽会持续激活内皮细胞上的弹性蛋白受体(16),产生具有血管舒张活性的一氧化氮*(18)。同时产生的超氧化物会导致过氧亚硝酸盐的形成,被还原型谷胱甘肽中和。这个持续数十年的过程很可能会损害细胞的抗自由基防御机制,并使内皮细胞失去一氧化氮*的血管舒张活性。因此,我们提出,弹性蛋白受体的持续激活以及自由基和裂解酶的产生很可能代表了动脉粥样硬化发生的起始过程。