Galectin-3 Marks Activated Macrophages in Failure-Prone Hypertrophied Hearts and Contributes to Cardiac Dysfunction

DOI Web Site 被引用文献18件
  • Umesh C. Sharma
    From the Experimental and Molecular Cardiology Laboratory, Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM) (U.C.S., S.P., J.H.v.B., B.S., H.J.G.M.C., Y.M.P.), the Department of Cardiothoracic Surgery, University Hospital Maastricht (U.C.S., T.J.v.B., J.M.), and the Department of Pathology, CARIM, University of Maastricht (J.P.M.C.), Maastricht, the Netherlands; and the Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians University,...
  • Saraswati Pokharel
    From the Experimental and Molecular Cardiology Laboratory, Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM) (U.C.S., S.P., J.H.v.B., B.S., H.J.G.M.C., Y.M.P.), the Department of Cardiothoracic Surgery, University Hospital Maastricht (U.C.S., T.J.v.B., J.M.), and the Department of Pathology, CARIM, University of Maastricht (J.P.M.C.), Maastricht, the Netherlands; and the Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians University,...
  • Thomas J. van Brakel
    From the Experimental and Molecular Cardiology Laboratory, Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM) (U.C.S., S.P., J.H.v.B., B.S., H.J.G.M.C., Y.M.P.), the Department of Cardiothoracic Surgery, University Hospital Maastricht (U.C.S., T.J.v.B., J.M.), and the Department of Pathology, CARIM, University of Maastricht (J.P.M.C.), Maastricht, the Netherlands; and the Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians University,...
  • Jop H. van Berlo
    From the Experimental and Molecular Cardiology Laboratory, Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM) (U.C.S., S.P., J.H.v.B., B.S., H.J.G.M.C., Y.M.P.), the Department of Cardiothoracic Surgery, University Hospital Maastricht (U.C.S., T.J.v.B., J.M.), and the Department of Pathology, CARIM, University of Maastricht (J.P.M.C.), Maastricht, the Netherlands; and the Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians University,...
  • Jack P.M. Cleutjens
    From the Experimental and Molecular Cardiology Laboratory, Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM) (U.C.S., S.P., J.H.v.B., B.S., H.J.G.M.C., Y.M.P.), the Department of Cardiothoracic Surgery, University Hospital Maastricht (U.C.S., T.J.v.B., J.M.), and the Department of Pathology, CARIM, University of Maastricht (J.P.M.C.), Maastricht, the Netherlands; and the Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians University,...
  • Blanche Schroen
    From the Experimental and Molecular Cardiology Laboratory, Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM) (U.C.S., S.P., J.H.v.B., B.S., H.J.G.M.C., Y.M.P.), the Department of Cardiothoracic Surgery, University Hospital Maastricht (U.C.S., T.J.v.B., J.M.), and the Department of Pathology, CARIM, University of Maastricht (J.P.M.C.), Maastricht, the Netherlands; and the Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians University,...
  • Sabine André
    From the Experimental and Molecular Cardiology Laboratory, Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM) (U.C.S., S.P., J.H.v.B., B.S., H.J.G.M.C., Y.M.P.), the Department of Cardiothoracic Surgery, University Hospital Maastricht (U.C.S., T.J.v.B., J.M.), and the Department of Pathology, CARIM, University of Maastricht (J.P.M.C.), Maastricht, the Netherlands; and the Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians University,...
  • Harry J.G.M. Crijns
    From the Experimental and Molecular Cardiology Laboratory, Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM) (U.C.S., S.P., J.H.v.B., B.S., H.J.G.M.C., Y.M.P.), the Department of Cardiothoracic Surgery, University Hospital Maastricht (U.C.S., T.J.v.B., J.M.), and the Department of Pathology, CARIM, University of Maastricht (J.P.M.C.), Maastricht, the Netherlands; and the Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians University,...
  • Hans -J. Gabius
    From the Experimental and Molecular Cardiology Laboratory, Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM) (U.C.S., S.P., J.H.v.B., B.S., H.J.G.M.C., Y.M.P.), the Department of Cardiothoracic Surgery, University Hospital Maastricht (U.C.S., T.J.v.B., J.M.), and the Department of Pathology, CARIM, University of Maastricht (J.P.M.C.), Maastricht, the Netherlands; and the Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians University,...
  • Jos Maessen
    From the Experimental and Molecular Cardiology Laboratory, Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM) (U.C.S., S.P., J.H.v.B., B.S., H.J.G.M.C., Y.M.P.), the Department of Cardiothoracic Surgery, University Hospital Maastricht (U.C.S., T.J.v.B., J.M.), and the Department of Pathology, CARIM, University of Maastricht (J.P.M.C.), Maastricht, the Netherlands; and the Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians University,...
  • Yigal M. Pinto
    From the Experimental and Molecular Cardiology Laboratory, Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM) (U.C.S., S.P., J.H.v.B., B.S., H.J.G.M.C., Y.M.P.), the Department of Cardiothoracic Surgery, University Hospital Maastricht (U.C.S., T.J.v.B., J.M.), and the Department of Pathology, CARIM, University of Maastricht (J.P.M.C.), Maastricht, the Netherlands; and the Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians University,...

説明

<jats:p> <jats:bold> <jats:italic>Background—</jats:italic> </jats:bold> Inflammatory mechanisms have been proposed to be important in heart failure (HF), and cytokines have been implicated to add to the progression of HF. However, it is unclear whether such mechanisms are already activated when hypertrophied hearts still appear well-compensated and whether such early mechanisms contribute to the development of HF. </jats:p> <jats:p> <jats:bold> <jats:italic>Methods and Results—</jats:italic> </jats:bold> In a comprehensive microarray study, galectin-3 emerged as the most robustly overexpressed gene in failing versus functionally compensated hearts from homozygous transgenic TGRmRen2-27 (Ren-2) rats. Myocardial biopsies obtained at an early stage of hypertrophy before apparent HF showed that expression of galectin-3 was increased specifically in the rats that later rapidly developed HF. Galectin-3 colocalized with activated myocardial macrophages. We found galectin-3-binding sites in rat cardiac fibroblasts and the extracellular matrix. Recombinant galectin-3 induced cardiac fibroblast proliferation, collagen production, and cyclin D1 expression. A 4-week continuous infusion of low-dose galectin-3 into the pericardial sac of healthy Sprague-Dawley rats led to left ventricular dysfunction, with a 3-fold differential increase of collagen I over collagen III. Myocardial galectin-3 expression was increased in aortic stenosis patients with depressed ejection fraction. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusions—</jats:italic> </jats:bold> This study shows that an early increase in galectin-3 expression identifies failure-prone hypertrophied hearts. Galectin-3, a macrophage-derived mediator, induces cardiac fibroblast proliferation, collagen deposition, and ventricular dysfunction. This implies that HF therapy aimed at inflammatory responses may need to be targeted at the early stages of HF and probably needs to antagonize multiple inflammatory mediators, including galectin-3. </jats:p>

収録刊行物

  • Circulation

    Circulation 110 (19), 3121-3128, 2004-11-09

    Ovid Technologies (Wolters Kluwer Health)

被引用文献 (18)*注記

もっと見る

詳細情報 詳細情報について

問題の指摘

ページトップへ