Smooth muscle cell apoptosis in aneurysmal, occlusive, and normal human aorta

Abstract

Purpose: Apoptosis is a universal physiologic mechanism of cell death that regulates mass and architecture in many tissues. Recently, apoptosis has been described as a feature in human vascular atherosclerosis and large-vessel structural integrity. To dissect mechanisms of aortic disease, we determined the extent of smooth muscle cell (SMC) apoptosis in aneurysmal, occlusive, and normal human aortic tissue.Methods: Tissue samples of aneurysmal, occlusive, and normal human infrarenal aorta were evaluated. DNA fragmentation detection methods and standard immunohistochemical techniques were used to determine apoptosis and SMC density in the medial layer of aortas. Apoptotic cells and SMC nuclei were counted by means of computer-generated image analysis. The results of all aortic subtypes were compared statistically by analysis of variance.Results: The samples evaluated were 16 aneurysmal, 6 occlusive, and 5 normal human aortas. α1-Actin immunostaining confirmed the predominance of SMC to the medial layer of all aortic samples. The SMC density was greatest within normal aortas with 291.0 ± 86.9 cells per high-powerfield (hpf) compared with occlusive aorta with 278.21 ± 117.7 cells per hpf (p = .43) and aneurysmal aorta with 271.76 ± 90.6 cells per hpf (p = .36). Correspondingly, apoptosis of SMCs was greatest within aneurysmal aortas, with 12.13 ± 11.0 cells per hpf compared with occlusive aortas with 1.29 ± 2.0 cells per hpf (p = .0007) and normal aortas with 3.75 ± 4.6 cells per hpf (p = .01).Conclusion: Apoptosis of SMCs is increased and SMC density is decreased within the medial layer of aneurysmal aortic tissue as compared with normal and occlusive aortas. Structural degeneration of aortic tissue at the cellular level contributes to aneurysm formation.