Abstract 15643: Differential Role of Endothelial vs. VSMC STIM1 in Angiogenesis and Arteriogenesis
Introduction: We previously reported that stromal-interacting molecule 1 (STIM1) plays opposing roles in vascular smooth muscle vs. endothelial cells in the regulation of vascular reactivity. In the present study, we determined the in vivo role of endothelial vs. VSMC STIM1 on angiogenesis and arteriogenesis in response to chronic ischemia.
Hypothesis: The specific deletion of STIM1 in endothelial cell blunts angiogenesis and arteriogenesis through the induction of the endoplasmic reticulum stress and oxidative stress. Whereas, the deletion of STIM1 specifically in SMC accelerates the angiogenesis and arteriogenesis in response to chronic ischemia via the reduction in oxidative stress and ER stress.
Methods: We specifically deleted STIM1 in endothelial cells (Stim1EC-/- mice) and in SMC (Stim1SMC-/- mice). The ischemic hind limb is the most representative model of peripheral artery disease and ischemic lower extremities that occur in diabetic patients. Stim1EC-/-, Stim1SMC-/-, and the wild type mice (WT: C57/Bl6) were submitted to chronic femoral artery ligation and then blood flow recovery was assessed once a week.
Results: The blood flow recovery, which reflects angiogenesis and arteriogenesis, in Stim1EC-/- was significantly blunted compared to Stim1SMC-/- and WT. Moreover, blood flow recovery in Stim1SMC-/- was earlier (2.5 weeks) than in WT (3 weeks). Western blot analysis in the ischemic hind limb muscle revealed the induction of the ER stress-CHOP and BIP, the increase in oxidative stress related to the augmented in the NADPH oxidase activity-Nox1-dependent, and the reduction in VEGFR2 and eNOS phosphorylation in Stim1EC-/- compared to Stim1SMC-/- and WT mice.
Conclusions: Our data demonstrated that specific deletion of STIM1 in endothelial cell impairs the basic mechanism of angiogenesis and arteriogenesis, while the specific deletion of STIM1 in VSMC accelerates angiogenesis and arteriogenesis, which will benefit type 2 diabetic patients with peripheral artery diseases and chronic ischemia in the lower extremities.
Author Disclosures: M. Ali: None. V. Mali: None. S. Haddox: None. M. Trebak: None. S. Belmadani: None. K. Matrougui: None.
- © 2016 by American Heart Association, Inc.