Resveratrol prevents palmitic-acid-induced cardiomyocyte contractile impairment

Can J Physiol Pharmacol. 2019 Dec;97(12):1132-1140. doi: 10.1139/cjpp-2019-0051. Epub 2019 Aug 2.

Abstract

Long-chain saturated fatty acids, especially palmitic acid (PA), contribute to cardiomyocyte lipotoxicity. This study tests the effects of PA on adult rat cardiomyocyte contractile function and proteins associated with calcium regulating cardiomyocyte contraction and relaxation. Adult rat cardiomyocytes were pretreated with resveratrol (Resv) and then treated with PA. For the reversal study, cardiomyocytes were incubated with PA prior to treatment with Resv. Cardiomyocyte contractility, ratio of rod- to round-shaped cardiomyocytes, and Hoechst staining were used to measure functional and morphological changes in cardiomyocytes. Protein expression of sarco-endoplasmic reticulum ATPase 2a (SERCA2a), native phospholamban (PLB) and phosphorylated PLB (pPLB ser16 and pPLB thr17), and troponin I (TnI) and phosphorylated TnI (pTnI) were measured. SERCA2a activity was also measured. Our results show that PA (200 μM) decreased the rate of cardiomyocyte relaxation, reduced the number of rod-shaped cardiomyocytes, and increased the number of cells with condensed nuclei; pre-treating cardiomyocytes with Resv significantly prevented these changes. Post-treatment with Resv did not reverse morphological changes induced by PA. Protein expression levels of SERCA2a, PLB, pPLBs, TnI, and pTnI were unchanged by PA or Resv. SERCA2a activity assay showed that Vmax and Iono ratio were increased with PA and pre-treatment with Resv prevented this increase. In conclusion, our results show that Resv protect cardiomyocytes from contractile dysfunction induced by PA.

Keywords: acide gras saturé; cardiomyocyte contractility; contractilité des cardiomyocytes; obesity; obésité; resveratrol; resvératrol; saturated fatty acid.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Gene Expression Regulation / drug effects
  • Male
  • Myocardial Contraction / drug effects*
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / physiology*
  • Palmitic Acid / adverse effects*
  • Rats
  • Rats, Sprague-Dawley
  • Resveratrol / pharmacology*
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism
  • Troponin I / metabolism

Substances

  • Troponin I
  • Palmitic Acid
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Resveratrol