Robert L
Laboratoire de Biologie Cellulaire, Paris, France.
Atherosclerosis. 1996 Jun;123(1-2):169-79. doi: 10.1016/0021-9150(96)05804-2.
Aging of the vascular wall, arteriosclerosis and focal lipidic plaques, atheromatosis, often occur together but may occur separately as lipidic lesions in young children or vascular aging in some animal species resistant to lipid-rich diet as the rat. Most theories of athero-arteriosclerosis claim an endothelial lesion for its initiation, without proposing a detailed mechanism. The elastin-laminin receptor present also on endothelial cells, mediates NO.-dependent vasorelaxation. It could be shown that chronic exposure to higher concentrations of the agonist, elastin peptides, present in human blood at microgram/ml concentrations, and also during aging, the receptor gets "uncoupled" from its transmission pathway (G-protein, PLC, PKC) but continues releasing free radicals as superoxyde. NO. and O2-. give peroxynitrite, a toxic anion, needing GSH for its neutralisation. GSH production decreases with age. This process decreases available NO. for vasorelaxation and could then contribute to age-dependent blood pressure increase and produce the endothelial lesions leading to the development of athero-arteriosclerosis.
血管壁老化、动脉硬化和局灶性脂质斑块（动脉粥样化）常常同时出现，但也可能单独发生，如在幼儿中出现脂质病变，或在某些对富含脂质饮食有抵抗力的动物物种（如大鼠）中出现血管老化。大多数动脉粥样硬化理论认为其起始于内皮损伤，但未提出详细机制。内皮细胞上也存在的弹性蛋白 - 层粘连蛋白受体介导一氧化氮（NO）依赖性血管舒张。可以证明，长期暴露于更高浓度的激动剂弹性蛋白肽（在人血液中以微克/毫升浓度存在），以及在衰老过程中，该受体与其传导途径（G蛋白、磷脂酶C、蛋白激酶C）“解偶联”，但继续释放超氧阴离子等自由基。NO和O₂⁻会生成过氧亚硝酸盐，一种有毒阴离子，需要谷胱甘肽（GSH）来中和。GSH的产生随年龄增长而减少。这个过程会减少用于血管舒张的可用NO，进而可能导致与年龄相关的血压升高，并产生导致动脉粥样硬化发展的内皮损伤。
