The adventitia and atherogenesis: removal initiates intimal proliferation in the rabbit which regresses on generation of a ‘neoadventitia’

Abstract

Removal of the carotid artery adventitia from rabbits induced the formation of an intimal hyperplastic lesion. In rabbits fed a normal diet, the lesion (measured as the intimal:medial ratio) was maximal by day 14 (0.456 ± 0.079, n = 5, P < 0.01) and thereafter, regressed towards control dimensions (0.037 ± 0.003, n = 14) by day 28 (0.080 ± 0.025, n = 7, P = 0.14). In rabbits fed a high cholesterol diet, the lesion was again maximal by day 14 (0.376 ± 0.056, n = 8, P < 0.01). Although some regression was seen, the lesion persisted to day 42 (0.272 ± 0.052, n = 8, P < 0.01). Electron microscopy and immunocytochemistry showed two types of lesion, (a) smooth muscle cell predominant on normal diet and, (b) macrophage predominant on high cholesterol diet. Smooth muscle cell predominant lesions underwent almost complete regression, whereas macrophage predominant lesions persisted. We propose that lesion formation may be initiated following the development of arterial wall hypoxia, secondary to excision of the adventitial vasa vasorum. Furthermore, we have devised a novel method to restore a highly vascular ‘neoadventitia’ to an artery whose adventitia has previously been removed, using loosely placed PVC tubing. We suggest this ‘neoadventitia’ was able to inhibit the formation of an intimal hyperplastic lesion and to promote regression of an already established lesion by restoring arterial wall oxygenation.