Endothelial GPR68 Is Essential for Arteriogenesis and Represents a Therapeutic Target in a Model of Peripheral Artery Disease - PubMed
5 hours ago
- #Arteriogenesis
- #Peripheral Artery Disease
- #GPR68
- GPR68, a shear-stress sensitive G protein-coupled receptor, is associated with increased risk of Peripheral Artery Disease (PAD).
- Endothelial-specific Gpr68 knockout mice (Gpr68 iECKO) showed impaired blood perfusion recovery, smaller collateral artery diameter, and worsened muscle injury after hindlimb ischemia (HLI).
- Defects in Gpr68 iECKO mice were linked to reduced perivascular CCR2+ macrophage recruitment and downregulation of Spp1, Ccl2, and Itgb3.
- Pharmacological activation of GPR68 with agonist Compound 71 enhanced monocyte adhesion to endothelial cells via increased SPP1 in vitro.
- In vivo, Compound 71 improved perfusion recovery and reduced ischemic tissue damage, suggesting GPR68 activation as a therapeutic strategy for PAD.