Qsox1 Contributes to Vascular Remodelling in Response to Hypertension.

INTRODUCTION

QSOX1, a sulfhydryl oxidase involved in arterial remodelling, has recently emerged as a biomarker for preeclampsia and acute heart failure. This study sought the cardiovascular roles of Qsox1 in response to angiotensin II (AngII)-induced hypertension.

METHODS

With approval from an Animal Ethics Committee (CNREEA#9), two models were developed: Qsox1-invalidated adult male mice (Qsox1-/-) mice (C57BL/6J background) and a tamoxifen-inducible, vascular smooth muscle cell (VSMC)-specific Qsox1 knockout. Hypertension was induced via AngII minipumps and trans-aortic constriction, with assessments of cardiac function, vessel size, and VSMC phenotype.

RESULTS

Qsox1-/- at baseline had lower blood pressure and exhibited a synthetic/immature VSMC phenotype in coronary arteries when compared to wild-type (WT). After 4 weeks of AngII infusion, Qsox1-/- mice showed acute heart failure, absent coronary media hypertrophy, and increased perivascular fibrosis compared to hypertensive WT controls (p < 0.01). VSMC-specific Qsox1 knockout leading to the lack of Qsox1 in VSMC only impairs the phenotype of these cells without effecting cardiac function in response to AngII.

CONCLUSION

These data implicate vascular Qsox1 in the adaptive mechanisms of VSMC to pressure overload such as the development of media hypertrophy.