Cholesterol oxidation derivatives and arterial endothelial damage.
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Three groups of New Zealand male while rabbits were given either 2.5 mg/kg of 25-hydroxycholesterol, cholestane-3 beta, 5 alpha, 6 beta-triol or vehicle only, intravenously. 24 h after treatment, the luminal surfaces of aortae of rabbits receiving 25-hydroxycholesterol were examined by scanning electron microscopy (SEM) and showed numerous balloon-like protrusions and crater-like defects as well as circulating, formed elements adhering on the luminal surface. The luminal surface of aortae of rabbits given cholestane-3 beta, 5 alpha, 6 beta-triol had similar but more frequent lesions when compared with those of the 25-hydroxycholesterol group. Microthrombi were occasionally found. The aortae of the control group had significantly fewer lesions. Transmission electron-microscopic studies showed intracytoplasmic vacuoles and diffuse subendothelial edema in the aortae of the two groups receiving the oxidation derivatives of cholesterol. The balloon-like protrusions and crater-like defects observed by SEM appeared to represent the initial sterol-induced endothelial cell injury. Repeated episodes of arterial injury followed by thrombus formation could eventually lead to atherosclerosis.