Experimental angiogenesis of arterial vasa vasorum

Abstract

Vasa vasorum are important sources of oxygen and nutrients to vascular tissues and their proliferation influences the pathogenesis of arterial disease; however, the regulation of their growth is poorly understood partly because of a lack of appropriate experimental models. We cuffed common carotid arteries of rabbits with segments of the contralateral carotid artery, a procedure that resulted in rapid and extensive elaboration of adventitial vasa vasorum and connective tissue. Endothelium-lined microvessels were observed at 1 week but vessels as large as 300 microm with an organizing media were common by 3 weeks. These vasa vasorum arose primarily from the vascular supply to contiguous tissues, but also from the carotid artery. This angiogenesis was accompanied by increased expression of the angiogenic factor, vascular endothelial growth factor (VEGF), in the invading connective tissue cells and increased expression of the transcriptional regulator of VEGF, hypoxia-inducible factor-1alpha (HIF-1alpha), in these connective tissues and in the cuffing artery. These findings are consistent with the hypothesis that upregulation of HIF-1alpha and VEGF expression drives angiogenesis of vasa vasorum in this model. This simple model may be amenable to the study of the development and elaboration of vasa vasorum, especially in the context of vascular pathologies.

Three‐dimensional arrangement of the vasa vasorum in explanted segments of the aged human great saphenous vein: Scanning electron microscopy and three‐dimensional morphometry of vascular corrosion casts

“…1) is found, whereas in the cuffed rabbit common carotid, a large undulating artery arose from the lumen of the carotid artery with no vein aside [see Fig. 5B in Bayer et al (2002)]. The vein ran at some distance away from the artery and was only slightly wider.…”

“…Recently, SEM of resin corrosion casts was used in an experimental rabbit model to give an overview of the amount of neovascularization of the vasa vasorum occurring between the rabbit carotid artery cuffed by a segment of its contralateral partner (Bayer et al, 2002). This study gave no detailed account of the 3D arrangement of the vasa vasorum within the wall of the artery.…”

“…If these results are compared with those of Bayer et al (2002), who were the first to demonstrate the adventitial vasa vasorum network of the rabbit common carotid artery, it should be noted that the studies deal with anatomically and physiologically different kinds of blood vessels (artery versus vein), different species (rabbit vs. human), differently sized vessels (1 vs. 4 mm), different aged vessels (months vs. 69 -73 years), different casting conditions (in vivo casting with vessel under normal pressure vs. ex vivo with vessel under zero intravasal pressure), and different injection routes (common carotid artery vs. single feeding artery of the vasa vasorum). Both studies, however, clearly show the rich vascularization of the vessel walls by the vasa vasorum [compare Fig.…”

“…As yet, only the vasa vasorum of the rabbit common carotid artery have been studied using SEM of vascular casts in an experimental model (Bayer et al, 2002). The present study is the first to analyze the vasa vasorum system in a vein.…”

“…Recently, it was shown that in an experimental model (common carotid artery of a rabbit) upregulation of hypoxia-induced factor-1␣ (HIF-1␣) and vascular endothelial growth factor (VEGF) expression drive angiogenesis of the vasa vasorum (Bayer et al, 2002) and that formation of adventitial vasa vasorum is induced through the HIF-1␣/ VEGF/Ets-1 (transcription factor) pathway in hypertension . It is assumed that blockade of this pathway is a possible means to prevent restenosis of grafted or stented vessels.…”