Tert-butylhydroquinone promotes angiogenesis and improves heart functions in rats after myocardial infarction

Clin Exp Hypertens. 2017;39(5):402-408. doi: 10.1080/10641963.2016.1259322. Epub 2017 May 23.

Abstract

Background: Hypertension is an increased risk of heart failure and acute myocardial infarction (MI). Tert-butylhydroquinone (tBHQ), as an antioxidant, shows multiple cardioprotective actions including the reduction in blood pressure. The aim of this study was to investigate whether and how tBHQ improves heart functions in rats.

Methods: The MI model was established in WKY and spontaneously hypertensive rats (SHRs) by ligation of left anterior descending coronary artery. Akt phosphorylation was examined by western blot in human umbilical vein endothelial cells (HUVECs) or in rats. Angiogenesis was assessed by immunohistochemistry and immunofluorescence. Heart function was determined by echocardiography.

Results: tBHQ increased Akt phosphorylation, promoted cell proliferations and migrations in HUVECs, which were abolished by Akt inhibitor wortmannin. In SHRs following MI, administration of tBHQ significantly increased Akt phosphorylation, promoted angiogenesis, reduced infarct size, and improved heart functions after 14 postoperative days. Importantly, these in vivo effects of tBHQ were ablated by wortmannin in SHRs.

Conclusion: tBHQ via Akt activation promotes ischemia-induced angiogenesis and improves heart functions in hypertensive rats. In perspectives, the application of tBHQ should be considered in patients with ischemic diseases such as MI and stroke.

Keywords: Akt; angiogenesis; hypertension; myocardial infarction; tBHQ.

MeSH terms

  • Androstadienes / pharmacology
  • Angiogenesis Inducing Agents / pharmacology
  • Angiogenesis Inducing Agents / therapeutic use*
  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Echocardiography
  • Heart / drug effects
  • Heart / physiopathology*
  • Heart Failure / physiopathology
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hydroquinones / pharmacology
  • Hydroquinones / therapeutic use*
  • Hypertension / complications
  • Hypertension / physiopathology
  • Male
  • Myocardial Infarction / diagnostic imaging
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / physiopathology
  • Neovascularization, Physiologic / drug effects*
  • Phosphorylation / drug effects
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Wortmannin

Substances

  • Androstadienes
  • Angiogenesis Inducing Agents
  • Antioxidants
  • Hydroquinones
  • Protein Kinase Inhibitors
  • 2-tert-butylhydroquinone
  • Proto-Oncogene Proteins c-akt
  • Wortmannin