Alterations in cardiac contractile and regulatory proteins contribute to age-related cardiac dysfunction in male rats

Physiol Rep. 2024 Aug;12(16):e70012. doi: 10.14814/phy2.70012.

Abstract

Aging is associated with cardiac contractile abnormalities, but the etiology of these contractile deficits is unclear. We hypothesized that cardiac contractile and regulatory protein expression is altered during aging. To investigate this possibility, left ventricular (LV) lysates were prepared from young (6 months) and old (24 months) Fischer344 rats. There are no age-related changes in SERCA2 expression or phospholamban phosphorylation. Additionally, neither titin isoform expression nor phosphorylation differed. However, there is a significant increase in β-isoform of the myosin heavy chain (MyHC) expression and phosphorylation of TnI and MyBP-C during aging. In permeabilized strips of papillary muscle, force and Ca2+ sensitivity are reduced during aging, consistent with the increase in β-MyHC expression and TnI phosphorylation. However, the increase in MyBP-C phosphorylation during aging may represent a mechanism to compensate for age-related contractile deficits. In isolated cardiomyocytes loaded with Fura-2, the peak of the Ca2+ transient is reduced, but the kinetics of the Ca2+ transient are not altered. Furthermore, the extent of shortening and the rates of both sarcomere shortening and re-lengthening are reduced. These results demonstrate that aging is associated with changes in contractile and regulatory protein expression and phosphorylation, which affect the mechanical properties of cardiac muscle.

Keywords: Ca2+ sensitivity; Ca2+ transient; cross‐bridge cycling; myosin binding protein C; myosin heavy chain; titin; troponin.

MeSH terms

  • Aging* / metabolism
  • Aging* / physiology
  • Animals
  • Calcium / metabolism
  • Calcium-Binding Proteins / metabolism
  • Calmodulin-Binding Proteins / metabolism
  • Carrier Proteins
  • Connectin / metabolism
  • Male
  • Myocardial Contraction* / physiology
  • Myocytes, Cardiac* / metabolism
  • Myosin Heavy Chains / metabolism
  • Phosphorylation
  • Rats
  • Rats, Inbred F344*
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism
  • Troponin I / metabolism

Substances

  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • phospholamban
  • Myosin Heavy Chains
  • Calcium-Binding Proteins
  • Connectin
  • Troponin I
  • Calcium
  • myosin-binding protein C
  • Calmodulin-Binding Proteins
  • Carrier Proteins