The biomarker plasma galectin-3 in advanced heart failure and survival with mechanical circulatory support devices

被引:22
作者
Erkilet, Guelsuem [1 ]
Oezpeker, Cenk [1 ]
Boethig, Dietmar [2 ]
Kramer, Frank [3 ]
Roefe, Daniela [1 ]
Bohms, Birte [1 ]
Morshuis, Michiel [1 ]
Gummert, Jan [1 ]
Milting, Hendrik [1 ]
机构
[1] Erich & Hanna Klessmann Inst Cardiovasc Rsearch &, Heart & Diabet Ctr NRW, Clin Thorac & Cardiovasc Surg, D-32545 Bad Oeynhausen, Germany
[2] Hannover Med Sch, Dept Heart Thorac Transplantat & Vasc Surg, Hannover, Germany
[3] Bayer Schering Pharma, Dept Target Discovery, Wuppertal, Germany
关键词
Galectin; 3; survival; biomarker; ventricular assist device; mechanical unloading; risk assessment; FIBROSIS;
D O I
10.1016/j.healun.2012.11.011
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND: During screening of heart transplantation (HTx) candidates supported by ventricular assist devices (VADs) for plasma biomarkers we found that galectin-3 (Gal-3) was increased pre-operatively in patients who later died during VAD support. Therefore, we analyzed the predictive value of plasma Gal-3 in the context of other potential clinical risk factors for death on device (DOD) in a cohort of 175 VAD patients. METHODS: We analyzed numerous clinical factors and plasma Gal-3 levels of 175 VAD patients before device implantation. Eighty VAD patients were successfully bridged to HTx (BTT, 45.7%), 80 (45.7%) died on VAD, 2 recovered on device (BTR, 1.1%). and 13 (7.4%) were still on device. Uni- and multivariate analyses were performed to assess the importance of Gal-3 with respect to other clinical factors. Myocardial gene expression of Gal-3 was investigated in apex samples by RT-PCR (n = 30) and Western blotting (n = 45). RESULTS: Plasma Gal-3 levels were higher in VAD patients than in controls (16.6 +/- 9.3 vs 9.5 +/- 3.9 ng/ml, p < 0.0001). Cox regression showed several clinical factors and type of VAD as independent outcome predictors, but Gal-3 was not among them. Using the regression equation we grouped patients according to their factor constellation for prediction of survival on VAD. We propose a calculation method for VAD survival prediction. Gal-3 mRNA and protein were detectable in failing myocardium, but did not correlate with its plasma concentration. CONCLUSIONS: Galectin-3 levels are associated with severe heart failure but do not provide sufficient discrimination for prediction of outcomes after VAD implantation. Importantly, we were unable to confirm myocardial tissue as a primary source for the observed plasma elevations of Gal-3. J Heart Lung Transplant 2013;32:221-230 (c) 2013 International Society for Heart and Lung Transplantation. All rights reserved.
引用
收藏
页码:221 / 230
页数:10
相关论文
共 18 条
[1]   The fibrosis marker galectin-3 and outcome in the general population [J].
de Boer, R. A. ;
van Veldhuisen, D. J. ;
Gansevoort, R. T. ;
Kobold, A. C. Muller ;
van Gilst, W. H. ;
Hillege, H. L. ;
Bakker, S. J. L. ;
van der Harst, P. .
JOURNAL OF INTERNAL MEDICINE, 2012, 272 (01) :55-64
[2]   Predictive value of plasma galectin-3 levels in heart failure with reduced and preserved ejection fraction [J].
de Boer, Rudolf A. ;
Lok, Dirk J. A. ;
Jaarsma, Tiny ;
van der Meer, Peter ;
Voors, Adriaan A. ;
Hillege, Hans L. ;
van Veldhuisen, Dirk J. .
ANNALS OF MEDICINE, 2011, 43 (01) :60-68
[3]   Galectin-3: a novel mediator of heart failure development and progression [J].
de Boer, Rudolf A. ;
Voors, Adriaan A. ;
Muntendam, Pieter ;
van Gilst, Wiek H. ;
van Veldhuisen, Dirk J. .
EUROPEAN JOURNAL OF HEART FAILURE, 2009, 11 (09) :811-817
[4]  
Grandio Emilio, 2011, CLIN CHEM, P58
[5]   Predictors of Death and Transplant in Patients With a Mechanical Circulatory Support Device: A Multi-institutional Study [J].
Holman, William L. ;
Kormos, Robert L. ;
Naftel, David C. ;
Miller, Marissa A. ;
Pagani, Frank D. ;
Blume, Elizabeth ;
Cleeton, Timothy ;
Koenig, Steven C. ;
Edwards, Leah ;
Kirklin, James K. .
JOURNAL OF HEART AND LUNG TRANSPLANTATION, 2009, 28 (01) :44-50
[6]   N-acetyl-seryl-aspartyl-lysyl-proline prevents cardiac remodeling and dysfunction induced by galectin-3, a mammalian adhesion/growth-regulatory lectin [J].
Liu, Yun-He ;
D'Ambrosio, Martin ;
Liao, Tang-dong ;
Peng, Hongmei ;
Rhaleb, Nour-Eddine ;
Sharma, Umesh ;
Andre, Sabine ;
Gabius, Hans-J. ;
Carretero, Oscar A. .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2009, 296 (02) :H404-H412
[7]   Prognostic value of galectin-3, a novel marker of fibrosis, in patients with chronic heart failure: data from the DEAL-HF study [J].
Lok, Dirk J. A. ;
Van Der Meer, Peter ;
Bruggink-Andre de la Porte, Pieta W. ;
Lipsic, Erik ;
Van Wijngaarden, Jan ;
Hillege, Hans L. ;
van Veldhuisen, Dirk J. .
CLINICAL RESEARCH IN CARDIOLOGY, 2010, 99 (05) :323-328
[8]   Differential regulation of Ca2+-dependent ATPase-activity in left ventricular myocardium during mechanical circulatory support [J].
Milting, H ;
Kassner, A ;
Böthig, D ;
Thieleczek, R ;
Kögler, H ;
Teucher, N ;
Meyer, HE ;
Arusoglu, L ;
Minami, K ;
Körfer, R ;
El Banayosy, A .
JOURNAL OF HEART AND LUNG TRANSPLANTATION, 2003, 22 (11) :1209-1216
[9]   Plasma biomarkers of myocardial fibrosis and remodeling in terminal heart failure patients supported by mechanical circulatory support devices [J].
Milting, Hendrik ;
Ellinghaus, Peter ;
Seewald, Michael ;
Cakar, Hamdin ;
Bohms, Birte ;
Kassner, Astrid ;
Koerfer, Reiner ;
Klein, Martina ;
Krahn, Thomas ;
Kruska, Lothar ;
El Banayosy, Aly ;
Kramer, Frank .
JOURNAL OF HEART AND LUNG TRANSPLANTATION, 2008, 27 (06) :589-596
[10]   Galectin-3 gene inactivation reduces atherosclerotic lesions and adventitial inflammation in ApoE-deficient mice [J].
Nachtigal, Maurice ;
Ghaffar, Abdul ;
Mayer, Eugene P. .
AMERICAN JOURNAL OF PATHOLOGY, 2008, 172 (01) :247-255