Intimal thickness and layering, and smooth muscle cell phenotypes in aorta of youth

Proneness to the lesions of atherosclerosis varies along the length and circumferential topography of the aorta. Smooth muscle cells, in particular those of the 'modulated' synthetic phenotype which are able to proliferate and synthesize matrix proteins, are considered to play an important role in lesion progression. We report on a study of the aortic intima at a lesion-prone site from abdominal aorta and a lesion-resistant site from thoracic aorta in young humans to determine (1) whether the histologic structure and the smooth muscle cell composition show quantitative differences between lesion-prone and lesion-resistant aortic sites; (2) whether there are gender differences, and (3) whether any differences increase in degree with increasing age in this young population. Material for this study was obtained as part of the NIH-funded multicenter study on Pathobiological Determinants of Atherosclerosis in Youth (PDAY) from autopsies of male and female subjects between the ages of 15 and 34, victims of unexpected sudden death, usually from trauma. The samples consisted of strips of abdominal and thoracic aorta, all derived from the same anatomical sites standardized in the PDAY studies. The thickness of total intima (TI) and its elastic hyperplastic (EH) layer was measured. Smooth muscle cells of all types (SMC) and separately those of the synthetic phenotype (SynSMC) were quantified in each site using immunohistochemical procedures in replicate sections of uniform thickness. The intima of the atherosclerotic lesion-prone dorsal half of the abdominal aorta (AD) shows significant differences from the lesion-resistant ventral half of thoracic aorta (TV) in that (1) its EH layer is significantly thicker; (2) its EH layer has a comparatively higher number of both total SMC and SynSMC, even when adjusted for intimal thickness, and (3) the age-related increase in thickness of both TI and EH layer of AD is much greater than that of TV.