Morphological studies on age changes of arterial walls and progression of atherosclerosis in human aorta and cerebral arteries, and effects of lipoproteins on proliferation of monkey aortic smooth muscle cells.

First, age changes and progression of atherosclerosis in the human aorta and cerebral arteries were studied morphologically. Secondly, effects of normolipemic high-density lipoprotein (HDL) on the proliferation of medial smooth muscle cells from the monkey aortas induced by hyperlipemic low-density lipoprotein (LDL) were investigated in vitro. Atherosclerosis developed in cellulofibrous intimal thickening in the human arteries. The first hitological evidence of the intimal proliferation of the middle cerebral arteries leading to the cellulofibrous intimal thickening was observed at bifurcations in 6 month-old fetuses. The initial event in the morphogenesis of the intimal thickening was believed to be the endothelial injuries caused by hemodynamic forces, namely, shear stress and turbulence of the blood flow at bifurcations of the arteries. The endothelial injuries resulted in increased endothelial permeability which permitted the entry of blood plasma into the tunica intima to proliferate myointimal cells (intimal smooth muscle cells) derived from the tunica media. The intimal thickening increased gradually with advancing age associated with the increase of the number of myointimal cells and of the amount of glycosaminoglycans and collagen and elastic fibers in the intima with individual variation. It might be considered that the cellulofibrous intimal thickening of the arteries, which was observed in normal subjects from fetal life up to adolescence and was regarded as the physiological development of the arterial wall, was actually a complex of changes resulting from mechanical injuries and related to age. Repeated proliferation of the intima formed the multilayered intimal thickening in cases over the age around ten. The so-called physiological intimal thickening also occurred in the aorta, markedly in the thoracic and abdominal aorta. The thickened intima was more vulnerable to injurious factors affecting the arterial walls than the less thickened intima. When hypertension, hyperlipemia or any kind of vascular injuries affected the arterial walls, enhancement of endothelial permeability and stagnation of the insudated blood plasma in the intima occurred more easily in the thickened intima. Particularly, the marginal areas of the thickened intima showed more increased permeability of the endothelial cells.