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

详细信息	查看全文 | 推荐本文 |

• 作者：Takeishi ; Yasuchika ; Jalili ; Thunder ; Hoit ; Brian D. ; Kirkpatrick ; Darryl L. ; Wagoner ; Lynne E. ; et. al.
• 关键词：G-proteins ; Heart failure ; Protein kinases ; Signal transduction ; Transplantation
• 刊名：Cardiovascular Research
• 出版年：2000
• 期刊代码：48_00086363
• 类别：med
• 出版时间：March, 2000
• 卷：45
• 期：4
• 页码：883-888
• 文件大小：285 K

摘要

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 Gαq 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 Gαq, phospholipase C β1, regulators of G protein signaling (RGS), sarcoplasmic reticulum Ca²⁺ ATPase, phospholamban and translocation of protein kinase C isoforms (α, β1, and β2). Results: The paired pre- and post- left ventricular assist device samples revealed that RGS2, a selective inhibitor of Gαq, was decreased (P<0.01), while the status of Gαq, phospholipase C β1, 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 β1 activation may contribute to improved mechanical function produced by left ventricular assist device support in human heart failure.