Engelberg H
California Arteriosclerosis Research Foundation, Beverly Hills, California 90210, USA.
Semin Thromb Hemost. 1997;23(2):159-66. doi: 10.1055/s-2007-996085.
Known atherosclerotic risk factors account today for only 50% of atherogenesis. Evidence is presented that a deficiency of endogenous heparin may account for the other half. Sensitive techniques have shown that there are trace quantities of heparin in plasma of humans. An inverse relationship has been found between plasma heparin levels and triglyceride-bearing Sf 12-400 lipoprotein, and a lower plasma heparin level could be an important determinant of atherogenesis fostering lipid abnormalities. Endogenous heparin also protects endothelium from harmful mediators that can impair normal function. Since atherosclerosis is a chronic inflammatory disease process, with monocyte-mediated release of cytokines and activation of integrins and phospholipase A2-mediated generation of platelet activating factor, heparin inhibits many of these events. Endogenous heparin activity thus opposes the effects of inflammatory activators. Heparin is also kown to inhibit complement activation and to suppress endothelin release from endothelial cells. In addition, endogenous heparin may suppress smooth muscle cell proliferation and decrease microthrombi formation on injured endothelial sites. All of these data seem to suggest that a deficiency of endogenous heparin or heparin-like substances predipose to atherosclerosis. It is conceivable that a genetically determined endogenous heparin deficiency is involved in atherosclerosis.
目前已知的动脉粥样硬化风险因素仅占动脉粥样硬化形成原因的50%。有证据表明，内源性肝素缺乏可能是另外50%的原因。敏感技术已显示，人体血浆中存在微量肝素。血浆肝素水平与携带甘油三酯的Sf 12 - 400脂蛋白之间呈负相关，血浆肝素水平较低可能是促进脂质异常的动脉粥样硬化形成的一个重要决定因素。内源性肝素还可保护内皮细胞免受能损害正常功能的有害介质的影响。由于动脉粥样硬化是一种慢性炎症性疾病过程，伴有单核细胞介导的细胞因子释放以及整合素和磷脂酶A2介导的血小板活化因子生成，肝素可抑制其中许多过程。因此，内源性肝素活性可对抗炎症激活剂的作用。肝素还已知可抑制补体激活，并抑制内皮细胞释放内皮素。此外，内源性肝素可能抑制平滑肌细胞增殖，并减少受损内皮部位的微血栓形成。所有这些数据似乎都表明，内源性肝素或类肝素物质缺乏易导致动脉粥样硬化。可以想象，基因决定的内源性肝素缺乏与动脉粥样硬化有关。
