Adventitia contribution in vascular tone: insights from adventitia‐derived cells in a tissue‐engineered human blood vessel

Abstract

Whether the adventitia component of blood vessels directly participates in the regulation of vascular tone remains to be demonstrated. We have recently developed a human tissue-engineered blood vessel comprising the three tunicae of a native blood vessel using the self-assembly approach. To investigate the role of the adventitia in the modulation of vascular tone, this tissue-engineering method was used to produce three vascular constructs from cells explanted and proliferated from donor vessel tunicae 1) an adventitia + a media, or only 2) an adventitia, or 3) a media. The vasoconstriction responses of these 3 constructs to endothelin, the most potent vasopressor known up-to-date, as well as to nonselective and selective agonists and antagonists, were compared. The adventitia contracted to endothelin-1, -2, whereas the media and the media+adventitia contracted to all three endothelins. Endothelin-induced contraction of the adventitia was dependent on ET(A) receptors, whereas that of the media and the adventitia+media was ET(A) and ET(B) receptor-dependent. RT-PCR studies corroborated these results. SNP induced a dose-dependent relaxation of the three tissue constructs. We also demonstrated that the endothelin-converting enzyme, responsible for the formation of the active endothelin peptides, was present and functional in the adventitia. In conclusion, this is the first direct demonstration that the adventitia has the capacity to contract and relax in response to vasoactive factors. The present study suggests that the adventitia of a blood vessel could play a greater role than expected in the modulation of blood vessel tone.

Morphological Reconstruction of Main Arteries by Perivascular Implantation of Sulfated Chitosan in Experimental Atherosclerosis

“…In the plaque mass there appear clusters of xanthoma cells, interstitial edema, subintimal and medial proliferation of smooth myocytes. On day 110 of cholesterol diet, these changes correspond to lipoidosis stage and are consistent with previously published data [4,7,17,18].…”

“…New methods of atherosclerosis prevention and treatment are developed through managing the process of atherogenic inflammation. The special role in the pathogenesis of atherosclerosis is given to the adventitia [6,7]. This vessel wall component is considered to be as important as the medial layer and the intima because it takes part in regulating the proliferation of smooth muscle cells of the medial and inner vessel layers during atherogenesis [8][9][10][11].…”

Tissue engineering of a collagen-based vascular media

“…Cell sheet tissue-engineered vascular medias (TEVM) have been extensively tested through use of a comprehensive panel of agents, 6 as well as investigations of the endothelin system. 7 Despite issues with cell culture, vasoactivity has been seen in TEVM that used adult smooth muscle cells [8][9][10] as well as TEVM using umbilical cord derived, 6,7,11,12 bone marrow progenitor, 13 and neonatal cells. 14,15 One reason why few groups have demonstrated function is that obtaining the number of cells necessary to make a TEVM requires extensive passaging of cells.…”

New perspectives on vascular wall signaling: role of perivascular adipocytes and fibroblasts

“…Evidence also suggests that the vascular adventitia may play an important role in vasomotor responses. The ability of the adventitia to respond to vasoactive peptides has been discovered recently in human tissue-engineered blood vessels [29] . On the other hand, the adventitia has been demonstrated to be a richer source of NO than the media, and that the adventitiaderived NO is able to activate guanylyl cyclase and vasodilatation within the media of the rat aorta [30,31] .…”