Mechanisms of stenosis after arterial injury

Abstract

The development of luminal narrowing in relationship to intimal thickening was investigated in rat common carotid artery denuded of endothelium. After denudation with a balloon embolectomy catheter endothelium was observed to regenerate from the ends of the denuded segment but not to cover the central third of the artery by 12 weeks. Cross-sections of denuded (Evans blue stained) and reendothelialized (white) areas showed that intimal thickening in the blue, but not the white, region progressively increased with time and was maximal between 4 and 12 weeks. Luminal narrowing was most pronounced at 2 weeks (75%) and less at 12 weeks (35%). The apparent discrepancy in these results was resolved by demonstrating that the vessel circumference in the blue region at the level of the internal elastic lamina was reduced at 2 weeks and the same as controls at 12 weeks; intravenous infusion of papaverine abolished this vasoconstriction of the left carotids at 2 weeks after injury. These results demonstrate that luminal narrowing early after injury is in large part due to smooth muscle contraction of the vessel and late due only to intimal thickening. During the period between 2 and 12 weeks the fraction of the intima occupied by smooth muscle cells decreased markedly, but the total volume due to smooth muscle cells remained relatively constant. Previous studies have demonstrated by DNA measurements that arterial wall cell number is the same at 2 and 12 weeks; these results taken together indicate that continued intimal thickening at late time points is due to synthesis and accumulation of connective tissue without further increase in smooth muscle cell number.