Molecular and cellular mechanisms of myocardial failure.
Myocardial remodeling is a central feature in the progression of myocardial failure. This process, which can be stimulated by factors that are increased as a result of myocardial dysfunction such as mechanical stress, angiotensin, and norepinephrine, consists of a variety of molecular and cellular events that can lead to important changes in myocardial structure and function (or phenotype). These alterations include hypertrophy and cellular apoptosis of myocytes, changes in the molecular phenotype of the myocardium with reinduction of a fetal gene program, and alterations in the quantity and composition of the extracellular matrix. Agents that counteract these factors, such as vasodilators, angiotensin-converting enzyme inhibitors, and beta-adrenergic antagonists, slow the progression of myocardial failure and are of clinical value in the treatment of heart failure. Several additional mechanisms have recently been identified that could also be important in mediating myocardial remodeling. These include oxidative stress, inflammatory cytokines, nitric oxide, endothelin, and peptide growth factors. It is likely that additional strategies to inhibit these mechanisms will exert beneficial effects on the process of myocardial remodeling and the development of clinical heart failure.
Colucci
W S
WS
Myocardial Biology Unit, Boston University School of Medicine, Massachusetts, USA.
D000818:Animals; D017209:Apoptosis; D003285:Contractile Proteins / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D018450:Disease Progression; D005109:Extracellular Matrix / Q000473:pathology; D015870:Gene Expression; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology*; D006984:Hypertrophy; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D009569:Nitric Oxide / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology
D003285:Contractile Proteins; D016207:Cytokines; D012333:RNA, Messenger; D009569:Nitric Oxide