HOMOCYSTINE-INDUCED ARTERIOSCLEROSIS - ROLE OF ENDOTHELIAL CELL INJURY AND PLATELET RESPONSE IN ITS GENESIS
HOMOCYSTINE-INDUCED ARTERIOSCLEROSIS - ROLE OF ENDOTHELIAL CELL INJURY AND PLATELET RESPONSE IN ITS GENESIS
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DOI：
10.1172/jci108520
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发表时间：
1976-01-01
影响因子：
15.9
通讯作者：
SCOTT, CR
中科院分区：
文献类型：
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作者：
HARKER, LA;ROSS, R;SCOTT, CR
在灵长类动物模型中，通过测量内皮细胞丢失和再生、血小板消耗和内膜损伤形成来确定同型半胱氨酸血症的动脉粥样硬化机制。实验分三组：对照组8只，3个月后15只。持续同型半胱氨酸血症，3个月后11只。合并同型半胱氨酸血症和口服双嘧达莫治疗。实验性同型半胱氨酸血症导致斑片状内皮细胞脱屑，约占主动脉表面的10%，尽管内皮细胞再生增加了25倍。潘生丁对血管内皮细胞的丢失和再生均无明显影响。同型半胱氨酸诱导的血管内皮细胞脱内皮化使血小板消耗量增加3倍，但被潘生丁抑制血小板功能中断。所有同型半胱氨酸血症动物都出现了典型的动脉硬化或动脉粥样硬化前病变，由平均10-15个细胞层的增殖的平滑肌细胞组成，周围环绕着大量的胶原、弹性纤维、糖胺聚糖，有时还包括脂质。潘生丁治疗可预防血管内膜病变的形成。同型半胱氨酸诱导的内皮细胞损伤通过血小板介导的血管内膜细胞增殖导致动脉硬化，而药物诱导的血小板功能障碍可以预防这一过程。
The atherogenic mechanism of homocystinemia was defined by measuring endothelial cell loss and regeneration, platelet consumption and intimal lesion formation in a primate model. Three groups of baboons [Papio cynocephalus] were studied: 8 control animals, 15 animals after 3 mo. of continuous homocystinemia and 11 animals after 3 mo. of combined homocystinemia and oral treatment with dipyridamole. Experimental homocystinemia caused patchy endothelial desquamation comprising about 10% of the aortic surface despite a 25-fold increase in endothelial cell regeneration. Neither endothelial cell loss nor regeneration was changed significantly by dipyridamole. Homocystine-induced vascular deendothelialization produced a 3-fold increase in platelet consumption that was interrupted by dipyridamole inhibition of platelet function. All homocystinemic animals developed typical arteriosclerotic or preatherosclerotic intimal lesions composed of proliferating smooth muscle cells averaging 10-15 cell layers surrounded by large amounts of collagen, elastic fibers, glycosaminoglycans and sometimes lipid. Intimal lesion formation was prevented by dipyridamole therapy. Homocystine-induced endothelial cell injury resulted in arteriosclerosis through platelet-mediated intimal proliferation of smooth muscle cells that can be prevented by drug-induced platelet dysfunction.