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

Objective: Left ventricular assist device support mechanically unloads the failing ventricle with resultant improvement in cardiac geometry and functi on in patients with end-stage heart failure. Activation of the G alpha g si gnaling pathway, including protein kinase C, appears to be involved in the progression of heart failure. Similarly down-regulation of Ca2+ cycling pro teins may contribute to contractile depression in this clinical syndrome. T hus we examined whether protein kinase C activation and decreased Ca2+ cycl ing protein levels could be reversed by left ventricular assist device supp ort. Methods: Left ventricular myocardial specimens were obtained from seve n patients during placement of left ventricular assist device and heart tra nsplantation. We examined changes in protein levels of G alpha q, phospholi pase C beta 1, regulators of G protein signaling (RGS), sarcoplasmic reticu lum Ca2+ ATPase, phospholamban and translocation of protein kinase C isofor ms (alpha, beta 1, and beta 2). Results: The paired pre- and post- left ven tricular 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, phosphol ipase C beta 1, RGS3 and RGS4 were unchanged after left ventricular assist device implantation. Translocation of protein kinase C isoforms remained un changed. Left ventricular assist device support increased sarcoplasmic reti culum Ca2+ ATPase protein level (P<0.01), while phospholamban abundance was unchanged. Conclusions: We conclude that altered protein expression and st oichiometry of the major cardiomyocyte Ca2+ cycling proteins rather than re duced phospholipase C beta 1 activation may contribute to improved mechanic al function produced by left ventricular assist device support in human hea rt failure. (C) 2000 Elsevier Science B.V. All rights reserved.