Downregulation of sarcoplasmic reticulum Ca2+-ATPase during progression of left ventricular hypertrophy

Q. I. Ming, Thomas R. Shannon, David E. Euler, Donald M Bers, Allen M. Samarel

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Abstract

To determine whether reduced sarcoplasmic reticulum (SR) Ca2+-adenosinetriphosphatase (ATPase) (SERCA2) activity contributes to delayed myocardial relaxation during chronic left ventricular hypertrophy (LVH) progression, LVH was produced in rats by abdominal aortic coarctation. Systolic and diastolic functions were assessed in vivo 8 and 16 wk after surgery, and compositional alterations in LV myocardium [SERCA2 concentration, myosin heavy chain (MHC) isoenzymes, and tissue collagen] were correlated with the development of prolonged isovolumic relaxation and impaired cardiac performance over time. Myocardial relaxation was prolonged in 8-wk banded rats, despite normal isovolumic systolic function and LV end-diastolic pressure (LVEDP). No significant alterations in SERCA2 protein, -MHC, or fibrillar collagen levels were observed at this early time point. In contrast, LV SERCA2, -MHC, and fibrillar collagen concentrations were all significantly altered in 16-wk banded rats. These late compositional changes were associated with reduced cardiac performance, as manifested by a significant elevation in LVEDP (14 ±2 mmHg). The 34% decrease in SERCA2 protein was associated with reduced SR Ca2+ uptake and an even greater reduction (76%) in SERCA2 mRNA. SERCA2 mRNA levels were also significantly reduced to 43 ±10% of sham-operated rats 8 wk after banding, despite unchanged SERCA2 protein levels and normal SR Ca2+ uptake. These results argue against a significant contribution of SERCA2 downregulation to the subtle alterations in myocardial relaxation observed in compensated LVH. However, the early reduction in SERCA2 mRNA levels may serve as a molecular marker for impaired cardiac performance during the transition from compensated LVH to heart failure.

Original languageEnglish (US)
JournalAmerican Journal of Physiology
Volume272
Issue number5 PART 2
StatePublished - 1997
Externally publishedYes

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Keywords

  • Calcium transport
  • Collagen
  • Fibrosis
  • Gene expression
  • Heart
  • Heart failure
  • Hemodynamics
  • Myocardial relaxation
  • Myosin

ASJC Scopus subject areas

  • Physiology (medical)

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