Homocystine-induced arteriosclerosis. The role of endothelial cell injury and platelet response in its genesis.
The atherogenic mechanism of homocystinemia has been defined by measuring endothelial cell loss and regeneration, platelet consumption, and intimal lesion formation in a primate model. Three groups of baboons were studied: (a) 8 control animals; (b) 15 animals after 3 mo of continuous homocystinemia; and (c) 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 threefold 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. We conclude that 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.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001161:Arteriosclerosis / Q000139:chemically induced*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival; D004176:Dipyridamole / Q000494:pharmacology; D004727:Endothelium / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D000882:Haplorhini; D006711:Homocystine / Q000009:adverse effects* / Q000097:blood* / Q000494:pharmacology; D008297:Male; D009130:Muscle, Smooth / Q000473:pathology; D010215:Papio; D010974:Platelet Aggregation / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology; D012038:Regeneration
D000893:Anti-Inflammatory Agents; D011743:Pyrimidines; D006711:Homocystine; D004176:Dipyridamole