Secreted frizzled-related protein 2, a novel mechanism to induce myocardial ischemic protection through angiogenesis

Dorothy E. Vatner, Marko Oydanich, Jie Zhang, Denis Babici, Stephen F. Vatner

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Our hypothesis is that Secreted Frizzled-Related Protein 2 (sFPR2) is an important mechanism mediating ischemic cardioprotection, since it is the most upregulated gene in the third window of ischemic preconditioning. One week after permanent coronary artery occlusion (CAO), sFRP2 TG mice exhibited a 49% higher LV ejection fraction and a 36% reduction in infarct size, p < 0.05, and reduced fibrosis in both adjacent and remote zones, along with an increase in collagen type III and a decrease in the collagen type I/III ratio compared with WTL. The ischemic cardioprotection was associated with increased angiogenesis and arteriogenesis, reflected by increased capillary and arteriolar proliferation in the ischemic zone, thereby preserving blood flow after CAO. The angiogenesis and arteriogenesis were mediated by cross talk between myocytes and endothelial cells. The mechanism for cardioprotection and angiogenesis/arteriogenesis did not involve a traditional vascular growth hormone, e.g., VEGF or FGF, but rather cTGF, and ATF6 through the stress signaling pathway. The ATF6 inhibitor, AEBSF, blocked the upregulation of cTGF and both the angiogenesis and arteriogenesis, resulting in abolition of the reduced infarct size and protection of cardiac function in the sFRP2 TG mouse following permanent CAO. sFRP2 is a novel mechanism to induce angiogenesis/arteriogenesis, mediated through the endoplasmatic reticulum (ER) stress signaling pathway, ATF6 and cTGF, which protects the heart from myocardial ischemia.

Original languageEnglish (US)
Article number48
JournalBasic research in cardiology
Volume115
Issue number4
DOIs
StatePublished - Jul 1 2020

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Keywords

  • Angiogenesis
  • Arteriogenesis
  • Cardioprotection
  • Secreted frizzled proteins

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