Figure 3

Natural history of the coronary atherosclerotic plaque in general population, including most of CHD patients. The starting point is a nodular hyperplasia of smooth muscle cells and elastic tissue with progressive fibrous replacement. No other changes as subendothelial lipo-protein-cholesterol storage, inflammatory process of any type, platelet aggregation and/or fibrin-platelet thrombi are found (A). Proteoglycan accumulation in the deep intima between tunica media and the fibrous cap is the second step (B). In this proteoglycan pool, lipo-protein/cholesterol cleft, in macrophages ("foam cells") and/or Ca⁺⁺ salts appear. Vascularization of the plaque and hemorrhage (C) follow. In the stage of proteoglycan accumulation, lympho-plasmacellular infiltrates occur in the adventitia and intima (C) with specific localization, around adventitial nerves closed to the tunica media (medial neuritis) (D, E). This natural history is totally different from that obtained experimentally by hypercholesterol diet in animals free of spontaneous atherosclerosis or in the small group of patients with familial hypercholesterolemia (F), in which transendothelial lipo-protein insudation is the starting point.