ヒト冠状動脈硬化の進展における膠原線維と内膜平滑筋細胞の役割

Abstract

Diffuse intimal thickening (DIT) has developed in the human coronary artery even in infants. Eccentric intimal thickening (EIT) evolves from DIT and may develop into atheromatous plaque. The purpose of this study is to clarify histological changes in the intima during the development of DIT to EIT or plaque in the human coronary artery.Materials for histometrical examination were obtamed from 253 autopsy cases. Histometrical studies were carried out on the proximal portions of the right coronary artery (seg. 1) and the left anterior descending artery (seg. 6). Thicknesses of the intima and the media and the I/M ratio were measured in all cases. In cases over 20 years of age, volume fractions (Vfs) of SMCs, collagen fibers, and elastic fibers in the intima were analyzed by the point-counting method. The number and density of SMCs were counted within the same area. DIT in both segs. 1 and 6 tended to increase with age. The I/M ratio in DIT increased with age but did not exceed 2. EIT increased more markedly with age than did DIT. Collagen fibers were the major component of the intima. Vfs of collagen fibers increased with successive changes from DIT to EIT and finally to plaque in contrast to the decrease in the density of SMCs when compared within the same age groups.In immunohistochemical studies, anti-muscle antigen (HHF35) positive SMCs were present in DIT as well as in EIT. A great number of anti-macrophage antigen positive foam cells were present in the plaque, particularly in plaque shoulder. Proliferating cell nuclear antigen (PCNA) positive cells were predominantly distributed in plaque shoulder, and prolyl hydroxylase (PH) positive cells were present within the same area. Anti-collagen Type I antibody reacted intensely to fibers in plaque, but fibers which reacted with the anti-collagen Type III antibody were randomly distributed in every layer of the arterial wall.In conclusion, DIT, EIT and plaque thickening in the coronary artery were chiefly due to SMC proliferation in the younger subjects; however, after the 4th decade, thickening was mainly due to an accumulation of collagen fibers.