APOLIPOPROTEIN(A) DEPOSITION IN ATHEROSCLEROTIC PLAQUES OF CEREBRAL VESSELS - A POTENTIAL ROLE FOR ENDOTHELIAL-CELLS IN LESION FORMATION

Atherosclerosis is the leading cause of death and serious morbidity in economically developed societies through its sequelae of coronary art ery and cerebrovascular disease. The causes and mechanisms of atherosc lerosis are still largely unknown. Serum levels of a lipoprotein, Lp(a ), have been shown, in retrospective and some prospective clinical stu dies, to be associated with increased risk of myocardial and cerebral infarction. The active part of Lp(a), apo(a), has >80% homology with p lasminogen; thus it may competitively inhibit the thrombolytic action of plasminogen and enhance thrombogenesis. Lp(a) has been shown to be deposited in the vascular wall of the aorta and coronary vessels, but its presence in the cerebral vessels has not yet been shown. Autopsy s pecimens of vessels of the circle of Willis from 23 patients were exam ined for degree of atherosclerosis and deposition of apo(a) by immunoh istochemistry with apo(a)-specific monoclonal antibodies. The amount o f apo(a) deposition in cerebral vessels correlated well with the degre e of cerebral atherosclerosis. Arterial deposition of apo(a) was found entirely within the endothelial cell and sub-endothelial cell layers. There was no staining within the media and adventitia, with the excep tion of staining within the endothelial cells of the vasa vasorum. Cor relation between the morphology of apo(a) deposition and plaque stage was found suggesting that detection of apo(a) in endothelial cells is an early event in the development of the atherosclerotic plaque of cer ebral vessels.