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Role of Stromal Interaction Molecule 1 in Arteriogenesis
Author(s) -
Frost Michaela,
Belmadani Souad,
Matrougui Khalid
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.03294
Subject(s) - arteriogenesis , vascular smooth muscle , stim1 , microbiology and biotechnology , mural cell , western blot , chemistry , biology , medicine , endocrinology , ischemia , biochemistry , endoplasmic reticulum , smooth muscle , gene
Arteriogenesis 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. Hypothesis We 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. Methods We isolated VSMC’s from mice with a genetic knockdown of STIM1 (VSMC Stim1−/− ) and also from wild‐type mice (VSMC Stim1+/+ ). 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. Results Under basal conditions, Western blot analysis revealed that anti‐arteriogenic TSP‐1, Hic‐5, and phosphorylated ERK1/2 expressions were significantly decreased in VSMC Stim1−/− when compared to VSMC Stim1+/+ . Western blotting also revealed that pro‐arteriogenic AMPK expression was increased in VSMC Stim1−/− relative to VSMC Stim1+/+ . Moreover, using real time PCR, we found that TSP‐1 mRNA levels were significantly reduced in VSMC Stim1−/− versus VSMC Stim1+/+ . Finally, the scratch‐assay injury revealed that VSMC Stim1−/− migrate more efficiently than VSMC Stim1+/+ . Conclusion Our 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 Information AHA‐34380220