Aging and arteriosclerosis. I. Development of myointimal hyperplasia after endothelial injury.

R J Hariri,D Coletti,D P Hajjar,M E Weksler,D R Alonso

doi:10.1084/jem.164.4.1171

Abstract

Old Fischer 344 rats are more susceptible to vascular lesions after arterial endothelial injury than are young animals. Thus, 20-26-mo-old Fischer 344 rats developed greater and more persistent intimal proliferative lesions than did 2-5-mo-old rats after aortic endothelial denudation. 3 d after deendothelialization, intimal thickness was increased two-fold in both old and young animals. However, 14 d after endothelial injury, intimal thickness had increased nearly five times in old animals, but had regressed to normal in young animals. Intimal thickness of young aortic grafts transplanted into young recipients did not differ significantly from adjacent host aorta or autotransplanted aortic segments 6 wk after surgery. In contrast, intimal thickness of old grafts transplanted into young recipients was eight times greater than adjacent young host aorta 6 wk after surgery. The density of cell nuclei in the intima of old grafts was also much greater than that in young grafts. Thus, in two experimental models of vascular injury, old rats have consistently had greater myointimal hyperplasia than young rats. The increased proliferative response of aortic smooth muscle cells after vascular injury of old animals may contribute to the increased prevalence of vascular disease with age.

Highlights

Materials and MethodsTwo microaneurysm clips were placed, -1 .5 cm apart, at the ends of the donor segment of the abdominal aorta and cut 1 .5 mm beyond the aneurysm clips
Intimal thickness of the injured segments of aorta in young rats had regressed and there was no significant difference in intimal thickness of injured and noninjured aorta
Old Fischer 344 rats are more susceptible to vascular lesions after arterial endothelial injury than are young animals

Summary

Materials and Methods

Two microaneurysm clips were placed, -1 .5 cm apart, at the ends of the donor segment of the abdominal aorta and cut 1 .5 mm beyond the aneurysm clips. This aortic cuff was irrigated with heparinized Ringers solution (1 u/ml) and the lumen was dilated by the insertion of the tips of microforceps and gentle dilation of the walls of the vessel. Endothelial cells of the abdominal aorta were removed by passing a wire catheter into the abdominal aorta with external pressure applied to the vessel. The aorta from the aortic arch to the iliac bifurcation was removed, opened longitudinally, and placed in formalin for 24-48 h before histologic processing. Data were from all analyzed statistically using the student t test

Results

Discussion

Summary