+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Quantification of Adventitial Vasa Vasorum Vascularization in Double-injury Restenotic Arteries

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.



          Accumulating evidence indicates a potential role of adventitial vasa vasorum (VV) dysfunction in the pathophysiology of restenosis. However, characterization of VV vascularization in restenotic arteries with primary lesions is still missing. In this study, we quantitatively evaluated the response of adventitial VV to vascular injury resulting from balloon angioplasty in diseased arteries.


          Primary atherosclerotic-like lesions were induced by the placement of an absorbable thread surrounding the carotid artery of New Zealand rabbits. Four weeks following double-injury induced that was induced by secondary balloon dilation, three-dimensional patterns of adventitial VV were reconstructed; the number, density, and endothelial surface of VV were quantified using micro-computed tomography. Histology and immunohistochemistry were performed in order to examine the development of intimal hyperplasia.


          Results from our study suggest that double injured arteries have a greater number of VV, increased luminal surface, and an elevation in the intima/media ratio (I/M), along with an accumulation of macrophages and smooth muscle cells in the intima, as compared to sham or single injury arteries. I/M and the number of VV were positively correlated ( R 2 = 0.82, P < 0.001).


          Extensive adventitial VV neovascularization occurs in injured arteries after balloon angioplasty, which is associated with intimal hyperplasia. Quantitative assessment of adventitial VV response may provide insight into the basic biological process of postangioplasty restenosis.

          Related collections

          Most cited references 31

          • Record: found
          • Abstract: found
          • Article: not found

          Regulation of angiogenesis by hypoxia: role of the HIF system.

          The regulation of angiogenesis by hypoxia is an important component of homeostatic mechanisms that link vascular oxygen supply to metabolic demand. Molecular characterization of angiogenic pathways, identification of hypoxia-inducible factor (HIF) as a key transcriptional regulator of these molecules, and the definition of the HIF hydoxylases as a family of dioxygenases that regulate HIF in accordance with oxygen availability have provided new insights into this process. Here we review these findings, and the role of HIF in developmental, adaptive and neoplastic angiogenesis. We also discuss the implications of oncogenic activation of extensive, physiologically interconnected hypoxia pathways for the tumor phenotype.
            • Record: found
            • Abstract: found
            • Article: not found

            Vascular endothelial growth factor enhances atherosclerotic plaque progression.

            Vascular endothelial growth factor (VEGF) can promote angiogenesis but may also exert certain effects to alter the rate of atherosclerotic plaque development. To evaluate this potential impact on plaque progression, we treated cholesterol-fed mice doubly deficient in apolipoprotein E/apolipoprotein B100 with low doses of VEGF (2 microg/kg) or albumin. VEGF significantly increased macrophage levels in bone marrow and peripheral blood and increased plaque area 5-, 14- and 4-fold compared with controls at weeks 1, 2 and 3, respectively. Plaque macrophage and endothelial cell content also increased disproportionately over controls. In order to confirm that the VEGF-mediated plaque progression was not species-specific, the experiment was repeated in cholesterol-fed rabbits at the three-week timepoint, which showed comparable increases in plaque progression.
              • Record: found
              • Abstract: found
              • Article: not found

              Inhibition of plaque neovascularization reduces macrophage accumulation and progression of advanced atherosclerosis.

              Plaque angiogenesis promotes the growth of atheromas, but the functions of plaque capillaries are not fully determined. Neovascularization may act as a conduit for the entry of leukocytes into sites of chronic inflammation. We observe vasa vasorum density correlates highly with the extent of inflammatory cells, not the size of atheromas in apolipoprotein E-deficient mice. We show atherosclerotic aortas contain activities that promote angiogenesis. The angiogenesis inhibitor angiostatin reduces plaque angiogenesis and inhibits atherosclerosis. Macrophages in the plaque and around vasa vasorum are reduced, but we detect no direct effect of angiostatin on monocytes. After angiogenesis blockade in vivo, the angiogenic potential of atherosclerotic tissue is suppressed. Activated macrophages stimulate angiogenesis that can further recruit inflammatory cells and more angiogenesis. Our findings demonstrate that late-stage inhibition of angiogenesis can interrupt this positive feedback cycle. Inhibition of plaque angiogenesis and the secondary reduction of macrophages may have beneficial effects on plaque stability.

                Author and article information

                Department of Vascular Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
                Author notes
                Address for correspondence: Dr. Hao Zhang, Department of Vascular Surgery, Ren Ji Hospital, Shanghai Jiao Tong University, 160 Pu Jian Road, Shanghai 200127, China E-Mail: chlzhcx@
                Chin Med J (Engl)
                Chin. Med. J
                Chinese Medical Journal
                Medknow Publications & Media Pvt Ltd (India )
                05 August 2015
                : 128
                : 15
                : 2090-2096
                Copyright: © 2015 Chinese Medical Journal

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

                Original Article


                Comment on this article