The dynamic interaction between matrix metalloproteinase activity and adverse myocardial remodeling.
The process of cardiac remodeling in response to cardiac injury and/or persistent elevations in wall stress generally relates to the progressive changes that occur in ventricular chamber dimensions and the various components of the myocardium, in particular the cardiomyocytes and the extracellular matrix. Volume overload, pressure overload or myocardial injury produces a sustained abnormal elevation in myocardial wall stress which initiates cardiac remodeling that frequently results in ventricular decompensation and heart failure. Regardless of the inciting cause, there appear to be three distinct phases to this process. In the initial phase, fibrillar collagen is partially degraded secondary to increased matrix metalloproteinase (MMP) activity. Following this, there is a chronic compensatory phase during which MMP activity and collagen concentration return to normal while cardiomyocyte size continues to progressively increase. The final phase is attained once the compensatory hypertrophic mechanisms are exhausted and is characterized by elevated MMP activity, marked ventricular dilatation and prominent fibrosis. Details of this progressive, dynamic remodeling process and its effect on ventricular function during chronic volume overload, chronic pressure overload and following myocardial infarction will be the focus of this article.
Janicki
Joseph S
JS
Department of Anatomy, Physiology & Pharmacology, Auburn University, Auburn, AL 36849-5517, USA. janicjs@auburn.edu
Brower
Gregory L
GL
Gardner
Jason D
JD
Chancey
Amanda L
AL
Stewart
James A
JA
D006332:Cardiomegaly / Q000503:physiopathology; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000502:physiology; D004789:Enzyme Activation; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009203:Myocardial Infarction / Q000209:etiology / Q000503:physiopathology*; D013318:Stroke Volume / Q000502:physiology; D016276:Ventricular Function / Q000502:physiology; D017725:Ventricular Pressure / Q000502:physiology; D020257:Ventricular Remodeling / Q000502:physiology*
D016207:Cytokines; D003094:Collagen; D020782:Matrix Metalloproteinases