Vasorin plays a critical role in vascular smooth muscle cells and arterial functions

Abstract

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 (VasnCRE‐ERT KO and VasnSMMHC‐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 VasnCRE‐ERT KO mice 21 days after tamoxifen injection was concomitant with decreases in blood pressure, angiotensin II levels, and vessel contractibility to phenylephrine. The VasnSMMHC‐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 Ca2+ 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.

Vasorin as an actor of bone turnover?

“…Vasn, a transmembrane protein involved in the pathophysiology of several organs including the large vessels and the kidney (Ikeda et al, 2004; Louvet et al, 2022; Man et al, 2018), is also expressed in the skeleton during development (Krautzberger et al, 2012). In the present study, we investigated the role of Vasn on long‐bone pathophysiology.…”

“…Accordingly, we reported the role of Vasn in vascular smooth muscle cells (VSMC) for vascular function maintenance (Louvet et al, 2022).…”

“…Vasn regulation is important during vessel repair as shown in a rat arterial injury model (Ikeda et al, 2004). Accordingly, we reported the role of Vasn in vascular smooth muscle cells (VSMC) for vascular function maintenance (Louvet et al, 2022).…”

The Oligomeric State of Vasorin in the Plasma Membrane Measured Non-Invasively by Quantitative Fluorescence Fluctuation Spectroscopy

“…Specific expression patterns of VASN vary depending on the developmental stage and physiological conditions. However, a consensus has emerged that VASN is highly expressed in smooth muscle cells and endothelial cells, the essential cell types in blood vessels [2,3]. Lately, VASN has been shown to play a key role in vascular development and homeostasis [4,5].…”

Enhanced vasorin signaling mitigates adverse cardiovascular remodeling

“…[2][3][4][5][6] In the aging cardiovascular system, a loss of balance between the pro-fibrotic signaling molecule, transforming growth factor-beta1 (TGF-β1), and the anti-fibrotic signaling molecule Vasorin (VASN), may play a determinant role in the initiation and progression of cardiovascular thickening, collagen deposition, and calcification, prompting age-associated adverse cardiovascular remodeling and triggering age-associated diseases. 4,[7][8][9][10][11] In fact, this imbalance has been shown to significantly contribute to cardiovascular fibrosis and stiffening with advancing age, development, or mechanical and metabolic insults. 4,7,9,10,12 During aging, both TGF-β1 and angiotensin II (Ang II) signaling increase in the cardiovascular system.…”