Regression of myointimal thickening following carotid endothelial injury and development of aortic foam cell lesions in long term hypercholesterolemic rats.
In an earlier report (Clowes AW, Ryan GB, Breslow JL, Karnovsky MJ: Lab Invest 35:6, 1976) we demonstrated that cholesterol feeding of rats led to hypercholesterolemia but no increase in smooth muscle cell (SMC) proliferation in right carotid arteries subjected to a standard endothelial injury when compared with normolipemic control animals. We have now examined these plaques at 6 months and 1 year after injury. In control animals, the carotid initimal thickening regressed to a relatively small, acellular, fibrous scar; there was no evidence of renewed endothelial injury and secondary SMC proliferation. Regression of the intimal thickening in the injured carotids of cholesterol-fed animals proceeded exactly as in control animals except for the accumulation of lipid. Unlike control animals, cholesterol-fed rats developed aortic intimal lesions containing extracellular lipid crystals and lipid-laden macrophages derived from mononuclear phagocytes in the blood. In addition to the lack of continued intimal SMC proliferation in the injured carotid, in the face of severe hypercholesterolemia the intima of the aorta did not contain mature SMC, or SMC-derived collagen and elastin. There was also no evidence of increased permeability to Evans blue, injected intravascularly. These findings suggest that hypercholesterolemia in the rat does not produce chronic endothelial injury, development of proliferative fibrous plaques, or enhancement of established SMC lesions.
D000818:Animals; D001011:Aorta / Q000473:pathology*; D002199:Capillary Permeability; D002339:Carotid Arteries / Q000473:pathology / Q000648:ultrastructure; D020212:Carotid Artery Injuries; D004727:Endothelium / Q000473:pathology; D005487:Foam Cells / Q000473:pathology*; D006937:Hypercholesterolemia / Q000150:complications* / Q000473:pathology; D008264:Macrophages / Q000473:pathology*; D008297:Male; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D009130:Muscle, Smooth / Q000473:pathology*; D051381:Rats; D013997:Time Factors; D014945:Wound Healing