Cholesterol and atheroma lipids activate complement and stimulate granulocytes. A possible mechanism for amplification of ischemic injury in atherosclerotic states.
Previous studies in experimental myocardial infarction have suggested that PMNs and plasma C might interact to intensify ischemic injury. From the finding of large amounts of activated C (specifically C5a) in the plasma of a patient with severe, ulcerating atherosclerosis and the cholesterol embolization syndrome, we postulated that crystalline cholesterol might activate C and thereby amplify infarctive tissue damage. On simple incubation, crystalline cholesterol--as well as lipids from atheromata--activated plasma C; such plasma then potently aggregated normal PMNs and provoked them to damage cultured endothelial cells in vitro. The active principle in cholesterol-incubated plasma was of molecular weight and antigenicity consistent with C5a (or C5a[desarginine]). Optimal activation required the presence of Ig and an intact classical C pathway. Exposure of plasma to crystalline cholesterol by ulceration of, or hemorrhage into, atherosclerotic plaques might therefore activate C in vivo, promoting further ischemic damage by causing leukostatic-leukoembolic compromise of small vessels downstream from the site of activation.
D001161:Arteriosclerosis / Q000503:physiopathology*; D002784:Cholesterol / Q000494:pharmacology*; D003167:Complement Activation / Q000187:drug effects*; D003182:Complement C5 / Q000502:physiology; D003327:Coronary Disease / Q000503:physiopathology*; D006098:Granulocytes / Q000187:drug effects*; D006801:Humans; D008055:Lipids / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
D003182:Complement C5; D008055:Lipids; D013481:Superoxides; D002784:Cholesterol