Alda‑1, an aldehyde dehydrogenase‑2 agonist, improves long‑term survival in rats with chronic heart failure following myocardial infarction

Mol Med Rep. 2018 Sep;18(3):3159-3166. doi: 10.3892/mmr.2018.9309. Epub 2018 Jul 24.

Abstract

Alda‑1, an aldehyde dehydrogenase 2 (ALDH2) agonist, has been demonstrated to reduce injury caused by acute myocardial infarction (MI) and ischemia/reperfusion. The present study aimed to investigate whether oral administration of Alda‑1 improved long‑term survival of rats with chronic heart failure (CHF) post‑MI. MI model rats treated daily with Alda‑1 exhibited an increase in 20‑week survival rate compared with untreated MI rats. Alda‑1 treatment decreased the heart weight/body weight ratio, collagen volume, left ventricular (LV) internal diameter at the end of diastole and LV internal diameter at the end of systole, while increasing LV ejection fraction with evident LV fractional shortening. Myocardial cell apoptosis index, the activity of caspase‑3 and the expression of cleaved‑caspase‑3 were also reduced by Alda‑1 treatment. The protective effects of Alda‑1 were associated with reduced 4‑hydroxynonenal accumulation. The results of the present study revealed that the long‑term treatment with Alda‑1 prevented the progression of ventricular remodeling and improved the long‑term survival of rats with CHF post‑MI.

MeSH terms

  • Aldehyde Dehydrogenase, Mitochondrial / metabolism*
  • Animals
  • Apoptosis / drug effects
  • Benzamides / therapeutic use*
  • Benzodioxoles / therapeutic use*
  • Cardiotonic Agents / therapeutic use*
  • Chronic Disease
  • Collagen / analysis
  • Collagen / metabolism
  • Enzyme Activators / therapeutic use*
  • Heart / drug effects
  • Heart Failure / drug therapy*
  • Heart Failure / etiology
  • Heart Failure / metabolism
  • Male
  • Myocardial Infarction / complications
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / metabolism
  • Myocardium / metabolism
  • Myocardium / pathology
  • Rats, Wistar

Substances

  • Benzamides
  • Benzodioxoles
  • Cardiotonic Agents
  • Enzyme Activators
  • N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide
  • Collagen
  • Aldehyde Dehydrogenase, Mitochondrial
  • Aldh2 protein, rat