Dynamic Changes in Lymphocyte GRK2 Levels in Cardiac Transplant Patients: A Biomarker for Left Ventricular Function

被引:32
作者
Bonita, Raphael E. [1 ]
Raake, Philip W. [2 ,3 ]
Otis, Nicholas J. [2 ,3 ]
Chuprun, J. Kurt [2 ,3 ]
Spivack, Talya
Dasgupta, Abhijit [4 ]
Whellan, David J. [1 ]
Mather, Paul J. [1 ]
Koch, Walter J. [1 ]
机构
[1] Thomas Jefferson Univ, Dept Med, Div Cardiol, Philadelphia, PA 19107 USA
[2] Thomas Jefferson Univ, George Zallie & Family Lab Cardiovasc Gene Therap, Philadelphia, PA 19107 USA
[3] Thomas Jefferson Univ, Ctr Translat Med, Philadelphia, PA 19107 USA
[4] Thomas Jefferson Univ, Div Biostat, Dept Pharmacol & Expt Therapeut, Philadelphia, PA 19107 USA
来源
CTS-CLINICAL AND TRANSLATIONAL SCIENCE | 2010年 / 3卷 / 01期
关键词
heart failure; biomarkers; GRK2; heart transplantation; BETA-ADRENOCEPTOR DENSITY; FAILING HUMAN HEART; FAILURE; EXPRESSION; RECEPTORS;
D O I
10.1111/j.1752-8062.2010.00176.x
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
100103 [病原生物学]; 100218 [急诊医学];
摘要
G protein-coupled receptor kinase 2 (GRK2), which is upregulated in the failing human myocardium, appears to have a role in heart failure (HF) pathogenesis. In peripheral lymphocytes, GRK2 expression has been shown to reflect myocardial levels. This study represents an attempt to define the role for GRK2 as a potential biomarker of left ventricular function in HF patients. We obtained blood from 24 HF patients before and after heart transplantation and followed them for up to 1 year, also recording hemodynamic data and histological results from endomyocardial biopsies. We determined blood GRK2 protein by Western blotting and enzyme-linked immunosorbent assay. GRK2 levels were obtained before transplant and at first posttransplant biopsy. GRK2 levels significantly declined after transplant and remained low over the course of the study period. After transplantation, we found that blood GRK2 signifi cantly dropped and remained low consistent with improved cardiac function in the transplanted heart. Blood GRK2 has potential as a biomarker for myocardial function in end-stage HF. Clin Trans Sci 2010; Volume #: 1-5.
引用
收藏
页码:14 / 18
页数:5
相关论文
共 13 条
[1]
Biomarkers in heart failure [J].
Braunwald, Eugene .
NEW ENGLAND JOURNAL OF MEDICINE, 2008, 358 (20) :2148-2159
[2]
BRISTOW MR, 1992, CLIN INVESTIGATOR, V70, pS105
[3]
HUMAN BETA-ADRENOCEPTORS - RELATION OF MYOCARDIAL AND LYMPHOCYTE BETA-ADRENOCEPTOR DENSITY [J].
BRODDE, OE ;
KRETSCH, R ;
IKEZONO, K ;
ZERKOWSKI, HR ;
REIDEMEISTER, JC .
SCIENCE, 1986, 231 (4745) :1584-1585
[4]
Relationship between alterations in lymphocyte and myocardial beta-adrenoceptor density in patients with left heart valvular disease [J].
Dzimiri, N ;
Moorji, A .
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 1996, 23 (6-7) :498-502
[5]
Genetic manipulation of myocardial β-adrenergic receptor activation and desensitization [J].
Hata, JA ;
Williams, ML ;
Koch, WJ .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2004, 37 (01) :11-21
[6]
Lymphocyte levels of GRK2 (βARK1) mirror changes in the LVAD-supported failing human heart:: Lower GRK2 associated with improved β-adrenergic signaling after mechanical unloading [J].
Hata, Jonathan A. ;
Williams, Matthew L. ;
Schroder, Jacob N. ;
Lima, Brian ;
Keys, Janelle R. ;
Blaxall, Burns C. ;
Petrofski, Jason A. ;
Jakoi, Andre ;
Milano, Carmelo A. ;
Koch, Walter J. .
JOURNAL OF CARDIAC FAILURE, 2006, 12 (05) :360-368
[7]
Elevated myocardial and lymphocyte GRK2 expression and activity in human heart failure [J].
Iaccarino, G ;
Barbato, E ;
Cipolletta, E ;
De Amicis, V ;
Margulies, KB ;
Leosco, D ;
Trimarco, B ;
Koch, WJ .
EUROPEAN HEART JOURNAL, 2005, 26 (17) :1752-1758
[8]
Ventricular assist devices as a bridge to transplant or recovery [J].
Kherani, AR ;
Maybaum, S ;
Oz, MC .
CARDIOLOGY, 2004, 101 (1-3) :93-103
[9]
Glucocorticoids reverse IL-1β-induced impairment of β-adrenoceptor-mediated relaxation and up-regulation of G-protein-coupled receptor kinases [J].
Mak, JCW ;
Hisada, T ;
Salmon, M ;
Barnes, PJ ;
Chung, KF .
BRITISH JOURNAL OF PHARMACOLOGY, 2002, 135 (04) :987-996
[10]
G protein-coupled receptor kinase 2 ablation in cardiac myocytes before or after myocardial infarction prevents heart failure [J].
Raake, Philip W. ;
Vinge, Leif E. ;
Gao, Erhe ;
Boucher, Matthieu ;
Rengo, Giuseppe ;
Chen, Xiongwen ;
DeGeorge, Brent R., Jr. ;
Matkovich, Scot ;
Houser, Steven R. ;
Most, Patrick ;
Eckhart, Andrea D. ;
Dorn, Gerald W., II ;
Koch, Walter J. .
CIRCULATION RESEARCH, 2008, 103 (04) :413-422