The integrin ligand SVEP1 regulates GPCR-mediated vasoconstriction via integrins α9β1 and α4β1.

ABSTRACT:

Background and purpose

Vascular tone is regulated by the relative contractile state of vascular smooth muscle cells (VSMCs). Several integrins directly modulate VSMC contraction by regulating calcium influx through L-type voltage-gated Ca²⁺ channels (VGCCs). Genetic variants in ITGA9, which encodes the α9 subunit of integrin α9β1, and SVEP1, a ligand for integrin α9β1, associate with elevated blood pressure; however, neither SVEP1 nor integrin α9β1 has reported roles in vasoregulation. We determined whether SVEP1 and integrin α9β1 can regulate VSMC contraction.

Experimental approach

SVEP1 and integrin binding were confirmed by immunoprecipitation and cell binding assays. Human induced pluripotent stem cell-derived VSMCs were used in in vitro [Ca²⁺ ]

SUBMITTER: Morris GE 

PROVIDER: S-EPMC9805129 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature