Alterations in Ca2+ cycling proteins and G alpha q signaling after left ventricular assist device support in failing human hearts

Cardiovasc Res. 2000 Mar;45(4):883-8. doi: 10.1016/s0008-6363(99)00415-0.

Abstract

Objective: Left ventricular assist device support mechanically unloads the failing ventricle with resultant improvement in cardiac geometry and function in patients with end-stage heart failure. Activation of the G alpha q signaling pathway, including protein kinase C, appears to be involved in the progression of heart failure. Similarly down-regulation of Ca2+ cycling proteins may contribute to contractile depression in this clinical syndrome. Thus we examined whether protein kinase C activation and decreased Ca2+ cycling protein levels could be reversed by left ventricular assist device support.

Methods: Left ventricular myocardial specimens were obtained from seven patients during placement of left ventricular assist device and heart transplantation. We examined changes in protein levels of G alpha q, phospholipase C beta 1, regulators of G protein signaling (RGS), sarcoplasmic reticulum Ca2+ ATPase, phospholamban and translocation of protein kinase C isoforms (alpha, beta 1, and beta 2).

Results: The paired pre- and post-left ventricular assist device samples revealed that RGS2, a selective inhibitor of G alpha q, was decreased (P < 0.01), while the status of G alpha q, phospholipase C beta 1, RGS3 and RGS4 were unchanged after left ventricular assist device implantation. Translocation of protein kinase C isoforms remained unchanged. Left ventricular assist device support increased sarcoplasmic reticulum Ca2+ ATPase protein level (P < 0.01), while phospholamban abundance was unchanged.

Conclusions: We conclude that altered protein expression and stoichiometry of the major cardiomyocyte Ca2+ cycling proteins rather than reduced phospholipase C beta 1 activation may contribute to improved mechanical function produced by left ventricular assist device support in human heart failure.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Calcium-Binding Proteins / metabolism
  • Calcium-Transporting ATPases / metabolism
  • Case-Control Studies
  • Female
  • GTP-Binding Proteins / metabolism*
  • Heart Failure / metabolism*
  • Heart Failure / therapy
  • Heart-Assist Devices*
  • Humans
  • Immunoblotting
  • Isoenzymes / metabolism
  • Male
  • Middle Aged
  • Myocardium / metabolism*
  • Protein Kinase C / metabolism*
  • RGS Proteins / metabolism*
  • Sarcoplasmic Reticulum / drug effects
  • Sarcoplasmic Reticulum / enzymology
  • Signal Transduction / physiology
  • Statistics, Nonparametric

Substances

  • Calcium-Binding Proteins
  • Isoenzymes
  • RGS Proteins
  • Rgs2 protein, mouse
  • phospholamban
  • Protein Kinase C
  • GTP-Binding Proteins
  • Calcium-Transporting ATPases