Abstract
IntroductionArteriogenesis is a vital process for maintaining blood supply in the event of abrupt obstruction of perfusion such as cardiac ischemia. Here, we sought to determine whether stromal‐interaction molecule 1 (STIM1) is a key molecular mechanism involved in arteriogenesis.HypothesisWe previously reported that disrupting STIM1 in vascular smooth muscle cells (VSMC’s) protects the heart against chronic ischemia; likely through the induction of arteriogenesis. We hypothesize that disrupting STIM1 specifically in VSMC’s results in greater cellular proliferation and migration, which subsequently aids in arteriogenesis.MethodsWe isolated VSMC’s from mice with a genetic knockdown of STIM1 (VSMCStim1−/−) and also from wild‐type mice (VSMCStim1+/+). We cultured these VSMC’s in vitro and measured well‐known anti‐angiogenic factors including; thrombospondin‐1 (TSP‐1), hydrogen peroxide‐inducible clone 5 (Hic‐5), and extracellular signal‐regulated kinase (ERK 1/2). Additionally, we assessed the levels of pro‐angiogenic agent, AMP‐activated protein kinase (AMPK). Lastly, we assessed VSMC proliferation and migration after scratch‐assay injury.ResultsUnder basal conditions, Western blot analysis revealed that anti‐arteriogenic TSP‐1, Hic‐5, and phosphorylated ERK1/2 expressions were significantly decreased in VSMCStim1−/− when compared to VSMCStim1+/+. Western blotting also revealed that pro‐arteriogenic AMPK expression was increased in VSMCStim1−/− relative to VSMCStim1+/+. Moreover, using real time PCR, we found that TSP‐1 mRNA levels were significantly reduced in VSMCStim1−/− versus VSMCStim1+/+. Finally, the scratch‐assay injury revealed that VSMCStim1−/− migrate more efficiently than VSMCStim1+/+.ConclusionOur data illustrated that disrupting STIM1 in VSMC’s attenuates arteriogenic antagonists and enhances pro‐arteriogenic factors indicating that STIM1 as an important mechanism in arteriogenesis. Therefore, lowering STIM1 expression specifically in VSMC’s could be a potential therapy for conditions such ischemic heart diseases.Support or Funding InformationAHA‐34380220
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