Vasorin Plays a Critical Role in Vascular Smooth Muscle Cells and Arterial Functions

Autor: Loïc Louvet, Gaëlle Lenglet, A. Michaela Krautzberger, Romuald Mentaverri, Frédéric Hague, Clara Kowalewski, Nassim Mahtal, Julie Lesieur, Anne‐Laure Bonnet, Caroline Andrique, Céline Gaucher, Cathy Gomila, Heinrich Schrewe, Pierre‐Louis Tharaux, Said Kamel, Catherine Chaussain, Isabelle Six
Přispěvatelé: Marrow Adiposity & Bone Lab - Adiposité Médullaire et Os - ULR 4490 (MABLab (ex-pmoi)), Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Laboratoire de Physiologie Cellulaire et Moléculaire - UR UPJV 4667 (LPCM), Université de Picardie Jules Verne (UPJV), Service d'Ingénierie Moléculaire pour la Santé (ex SIMOPRO) (SIMoS), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Chimie Bio-Organique et de Marquage (SCBM), Pathologies, imagerie et biothérapies oro-faciales = Orofacial pathologies, imaging and biotherapies (URP 2496), Université Paris Cité (UPCité), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UFR Odontologie [Santé] - Université Paris Cité (UFR Odontologie UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Journal of Cellular Physiology
Journal of Cellular Physiology, 2022, ⟨10.1002/jcp.30838⟩
ISSN: 0021-9541
1097-4652
DOI: 10.1002/jcp.30838⟩
Popis: International audience; Within the cardiovascular system, the protein vasorin (Vasn) is predominantly expressed by vascular smooth muscle cells (VSMCs) in the coronary arteries and the aorta. Vasn knockout (Vasn(-/-) ) mice die within 3 weeks of birth. In the present study, we investigated the role of vascular Vasn expression on vascular function. We used inducible Vasn knockout mice (Vasn(CRE-ERT KO) and Vasn(SMMHC-CRE-ERT2 KO) , in which respectively all cells or SMCs only are targeted) to analyze the consequences of total or selective Vasn loss on vascular function. Furthermore, in vivo effects were investigated in vitro using human VSMCs. The death of Vasn(CRE-ERT KO) mice 21 days after tamoxifen injection was concomitant with decreases in blood pressure, angiotensin II levels, and vessel contractibility to phenylephrine. The Vasn(SMMHC-CRE-ERT2 KO) mice displayed concomitant changes in vessel contractibility in response to phenylephrine and angiotensin II levels. In vitro, VASN deficiency was associated with a shift toward the SMC contractile phenotype, an increase in basal intracellular Ca(2+) levels, and a decrease in the SMCs' ability to generate a calcium signal in response to carbachol or phenylephrine. Additionally, impaired endothelium-dependent relaxation (due to changes in nitric oxide signaling) was observed in all Vasn knockout mice models. Our present findings highlight the role played by Vasn SMC expression in the maintenance of vascular functions. The mechanistic experiments suggested that these effects are mediated by SMC phenotype switching and changes in intracellular calcium homeostasis, angiotensin II levels, and NO signaling.
Databáze: OpenAIRE
Externí odkaz: