Endothelial deletion of PKCδ prevents VEGF inhibition and restores blood flow reperfusion in diabetic ischemic limb.

ABSTRACT:

Aims

Peripheral artery disease is a complication of diabetes leading to critical hindlimb ischemia. Diabetes-induced inhibition of VEGF actions is associated with the activation of protein kinase Cδ (PKCδ). We aim to specifically investigate the role of PKCδ in endothelial cell (EC) function and VEGF signaling.

Methods

Nondiabetic and diabetic mice, with (ec-Prkcd^-/-) or without (ec-Prkcd^f/f) endothelial deletion of PKCδ, underwent femoral artery ligation. Blood flow reperfusion was assessed up to 4 weeks post-surgery. Capillary density, EC apoptosis and VEGF signaling were evaluated in the ischemic muscle. Src homology region 2 domain-containing phosphatase-1 (SHP-1) phosphatase activity was assessed in vitro using primary ECs.

SUBMITTER: Croteau L 

PROVIDER: S-EPMC8481738 | biostudies-literature | 2021 Mar-Apr

REPOSITORIES: biostudies-literature