Role of the Vasa Vasorum and Vascular Resident Stem Cells in Atherosclerosis

Abstract

Atherosclerosis is considered an “inside-out” response, that begins with the dysfunction of intimal endothelial cells and leads to neointimal plaque formation. The adventitia of large blood vessels has been recognized as an active part of the vessel wall that is involved in the process of atherosclerosis. There are characteristic changes in the adventitial vasa vasorum that are associated with the development of atheromatous plaques. However, whether vasa vasorum plays a causative or merely reactive role in the atherosclerotic process is not completely clear. Recent studies report that the vascular wall contains a number of stem/progenitor cells that may contribute to vascular remodeling. Microvessels serve as the vascular niche that maintains the resident stem/progenitor cells of the tissue. Therefore, the vasa vasorum may contribute to vascular remodeling through not only its conventional function as a blood conducting tube, but also its new conceptual function as a stem cell reservoir. This brief review highlights the recent advances contributing to our understanding of the role of the adventitial vasa vasorum in the atherosclerosis and discusses new concept that involves vascular-resident factors, the vasa vasorum and its associated vascular-resident stem cells, in the atherosclerotic process.

Immortalized multipotent pericytes derived from the vasa vasorum in the injured vasculature. A cellular tool for studies of vascular remodeling and regeneration

“…18,32 Indeed, the number of mPCs increases in the adventitia of injured femoral arteries, and these cells participate in the restenotic response to arterial injury. 33,17 Along with these findings, we established mPCs, which have unique features as discussed below, at a relatively high proportion among immortalized PC lines (three of six lines). Therefore, it is suggested that the mPC is a specific PC subtype associating with the growing adventitial vasa vasorum and contributes to vascular remodeling.…”

“…14 Recent studies have demonstrated the existence of adventitial stem/progenitor cells, including mPCs as a system reservoir for tissue-resident stem cells. [15][16][17] In a vascular remodeling setting following vascular injury, in parallel with adventitial neovascularization, adventitial progenitor cells start a process of proliferation, migration and differentiation and contribute to vascular remodeling. 18,19 Therefore, the growing vasa vasorum may serve as a vascular niche for adventitial stem cells, including mutipotent PCs, and plays an active role in vascular remodeling.…”

“…18,19 Therefore, the growing vasa vasorum may serve as a vascular niche for adventitial stem cells, including mutipotent PCs, and plays an active role in vascular remodeling. 17 A transgenic mouse harboring the temperature-sensitive SV40 large T-antigen gene (tsSV40Tg mouse) expresses inactive tsSV40 in all tissues. When the isolated cells are cultured at 331C, cells can be easily immortalized by the activation of tsSV40.…”

Multidimensional Contribution of Matrix Metalloproteinases to Atherosclerotic Plaque Vulnerability: Multiple Mechanisms of Inhibition to Promote Stability

“…Advanced atherosclerotic lesions may become infiltrated by vessels of the vasa vasorum in response to hypoxia and inflammatory mediators [124]. This centripetal angiogenesis is frequently localized to the plaque shoulders, suspected to begin early in lesion progression beyond fatty streaks, and regarded as the likely source of intraplaque hemorrhage, providing another mechanism for plaque instability [3,125,126,127].…”

Heterogeneity in vascular smooth muscle cell embryonic origin in relation to adult structure, physiology, and disease

“…Like the epicardium, the adventitia is a connective tissue-rich protective layer. In the largest vessels such as the aorta, the adventitia contains the vasa vasorum which is the source of oxygenated blood for the media of these large vessels (Kawabe and Hasebe, 2014). While rich in connective tissue, the adventitia of the major vessels also contains a Sca1 + cell population capable of giving rise to VSMCs (Passman et al, 2008).…”