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

Karina Laflamme^*, Charles J. Roberge^*, Guillaume Grenier^*, Murielle Rémy-Zolghadri^*, Stéphanie Pouliot^*, Kathleen Baker^*, Raymond Labbé^*, Pédro D’Orléans-Juste, François A. Auger^* and Lucie Germain^*,1

^* Laboratoire d’Organogénèse Expérimentale/LOEX, Hôpital Saint-Sacrement du Centre Hospitalier Affililié Universitaire de Quebec and Department of Surgery, Laval University, Québec, Canada; and

Institute of Pharmacology, Medical School, Sherbrooke University, Sherbrooke, Canada

¹Correspondence: Laboratoire d’Organogénése Expérimentale, Hôpital du Saint-Sacrement du CHA, 1050 Chemin Ste-Foy, Québec, QC G1S 4L8, Canada. E-mail: lucie.germain{at}chg.ulaval.ca

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.—Laflamme, K., Roberge, C. J., Grenier, G., Rémy-Zolghadri, M., Pouliot, S., Baker, K., Labbé, R., D’Orléans-Juste, P., Auger, F. A., Germain, L. Adventitia contribution in vascular tone: insights from adventitia-derived cells in a tissue-engineered human blood vessel.

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