Role of matrix metalloproteinases in hypertension-associated cardiac fibrosis.
OBJECTIVE
The potential contribution of alterations in matrix metalloproteinase activity to the development of myocardial fibrosis in hypertensive heart disease is reviewed.


RESULTS
A number of experimental and clinical studies provide information on alterations in the balance between matrix metalloproteinase-1 or collagenase and tissue inhibitor of matrix metalloproteinases-1, which result in depressed proteolytic activity of the enzyme in animals and humans with hypertensive heart disease. While some recent data point to a genetic origin of such an imbalance, other findings suggest that depressed collagenase activity may contribute to disturbances of cardiac function via facilitation of myocardial fibrosis. On the other hand, emerging information is providing the basis for the notion that other matrix metalloproteinases, namely gelatinases, may participate in the process of myocardial fibrosis through stimulation of fibrillar collagen synthesis. Some fragmented matrix peptides or matrikines may be the mediators of the profibrotic action of these matrix metalloproteinases.


CONCLUSIONS
The matrix metalloproteinases represent an important biological system within the myocardium designed to maintain the complex and dynamic microenvironment of the extracellular matrix. Improved understanding of how this system is dysregulated in hypertensive heart disease will probably provide new insights into, and strategies for, heart failure.
López
Begoña
B
Area of Cardiovascular Pathophysiology, Centre for Applied Medical Research, and Department of Cardiology and Cardiovascular Surgery, University Clinic, School of Medicine University of Navarra, Pamplona, Spain.
González
Arantxa
A
Díez
Javier
J
D005355:Fibrosis; D006331:Heart Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000150:complications*; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D020782:Matrix Metalloproteinases / Q000502:physiology*; D019714:Tissue Inhibitor of Metalloproteinases / Q000502:physiology
D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases