Matrix metalloproteinases in the progression of heart failure - Potential therapeutic implications

被引:31
作者
Li, YY [1 ]
Feldman, AM [1 ]
机构
[1] Univ Pittsburgh, Sch Med, Cardiovasc Inst, Pittsburgh, PA 15213 USA
关键词
D O I
10.2165/00003495-200161090-00002
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Matrix metalloproteinases (MMPs) are a family of functionally related zinc-containing enzymes that denature and degrade fibrillar collagens and other components of the extracellular matrix. Myocardial extracellular matrix remodelling and fibrosis regulated by MMPs are believed to be important contributors to the progression of heart failure. The role of MMPs in cardiac fibrosis and the progression of heart failure, along with the possibility of halting the progression of heart failure by modulating extracellular matrix remodelling are important issues under intense study. MMPs are increased in the failing hearts of both animal models and patients with heart failure. MMP inhibition may therefore modulate extracellular matrix remodelling and the progression of heart failure. It is a great advantage that various MMP inhibitors have been developed initially for the treatment of cancer, arthritis and other diseases believed to be associated with increased MMP activity. Several preclinical studies have shown that treatment of heart failure in animal models with MMP inhibitors results in less collagen matrix damage, favourable extracellular matrix remodelling, and improved cardiac structure and function. The results suggest that modulation of MMP activity can prevent myocardial dysfunction and the progression of heart failure through alterations in the remodelling process of extracellular matrix and the left ventricle. Although these promising results suggest potential benefits of MMP inhibition for human heart failure, no clinical data evaluating MMP inhibitors in heart failure have been reported. As the preclinical evidence continues to grow and the potential of MMP inhibition for the treatment of heart failure continues to unfold, MMP inhibition may prove to be an effective treatment for heart failure.
引用
收藏
页码:1239 / 1252
页数:14
相关论文
共 119 条
[1]  
Abbruzzese TA, 1998, SURGERY, V124, P328, DOI 10.1067/msy.1998.91338
[2]   Expression of matrix metalloproteinase 9 (96-kd gelatinase B) in human rheumatoid arthritis [J].
Ahrens, D ;
Koch, AE ;
Pope, RM ;
SteinPicarella, M ;
Niedbala, MJ .
ARTHRITIS AND RHEUMATISM, 1996, 39 (09) :1576-1587
[3]  
Alvarez RJ, 2000, CIRCULATION, V102, P501
[4]   STRUCTURAL BASIS OF END-STAGE FAILURE IN ISCHEMIC CARDIOMYOPATHY IN HUMANS [J].
BELTRAMI, CA ;
FINATO, N ;
ROCCO, M ;
FERUGLIO, GA ;
PURICELLI, C ;
CIGOLA, E ;
QUAINI, F ;
SONNENBLICK, EH ;
OLIVETTI, G ;
ANVERSA, P .
CIRCULATION, 1994, 89 (01) :151-163
[5]  
BENDER SL, 1999, Patent No. 6008243
[6]   The matrix metalloproteinase inhibitor BB-94 limits expansion of experimental abdominal aortic aneurysms [J].
Bigatel, DA ;
Elmore, JR ;
Carey, DJ ;
Cizmeci-Smith, G ;
Franklin, DP ;
Youkey, JR .
JOURNAL OF VASCULAR SURGERY, 1999, 29 (01) :130-138
[7]   MATRIX METALLOPROTEINASES - A REVIEW [J].
BIRKEDALHANSEN, H ;
MOORE, WGI ;
BODDEN, MK ;
WINDSOR, LJ ;
BIRKEDALHANSEN, B ;
DECARLO, A ;
ENGLER, JA .
CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE, 1993, 4 (02) :197-250
[8]   ENHANCED DEPOSITION OF PREDOMINANTLY TYPE-I COLLAGEN IN MYOCARDIAL-DISEASE [J].
BISHOP, JE ;
GREENBAUM, R ;
GIBSON, DG ;
YACOUB, M ;
LAURENT, GJ .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 1990, 22 (10) :1157-1165
[9]   ASTACINS, SERRALYSINS, SNAKE-VENOM AND MATRIX METALLOPROTEINASES EXHIBIT IDENTICAL ZINC-BINDING ENVIRONMENTS (HEXXHXXGXXH AND MET-TURN) AND TOPOLOGIES AND SHOULD BE GROUPED INTO A COMMON FAMILY, THE METZINCINS [J].
BODE, W ;
GOMISRUTH, FX ;
STOCKLER, W .
FEBS LETTERS, 1993, 331 (1-2) :134-140
[10]   The ageing spontaneously hypertensive rat as a model of the transition from stable compensated hypertrophy to heart failure [J].
Boluyt, MO ;
Bing, OHL ;
Lakatta, EG .
EUROPEAN HEART JOURNAL, 1995, 16 :19-30