Role of proteases in the pathophysiology of cardiac disease.
Cardiovascular disease is a major cause of death and thus a great deal of effort has been made in salvaging the diseased myocardium. Although various factors have been identified as possible causes of different cardiac diseases such as heart failure and ischemic heart disease, there is a real need to elucidate their role for the better understanding of the cardiac disease pathology and formulation of strategies for developing newer therapeutic interventions. In view of the intimate involvement of different types of proteases in maintaining cellular structure, the role of proteases in various cardiac diseases has become the focus of recent research. Proteases are present in the cytosol as well as are localized in a number of subcellular organelles in the cell. These are known to use extracellular matrix, cytoskeletal, sarcolemmal, sarcoplasmic reticular, mitochondrial and myofibrillar proteins as substrates. Work from different laboratories using a wide variety of techniques has shown that the activation of proteases causes alterations of a number of specific proteins leading to subcellular remodeling and cardiac dysfunction. Inhibition of protease action by different drugs and agents, therefore, has a clinical relevance and is expected to form a part of new treatment paradigm for improving heart function. This review examines the biochemistry and localization of some of the proteases in the cardiac tissue in addition to identification of the sites of action of some protease inhibitors.
Singh
Raja B
RB
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Dandekar
Sucheta P
SP
Elimban
Vijayan
V
Gupta
Suresh K
SK
Dhalla
Naranjan S
NS
D000818:Animals; D002154:Calpain / Q000378:metabolism; D006331:Heart Diseases / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology*; D006801:Humans; D008247:Lysosomes / Q000201:enzymology; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008929:Mitochondria, Heart / Q000201:enzymology; D009124:Muscle Proteins / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010447:Peptide Hydrolases / Q000145:classification / Q000502:physiology*; D011480:Protease Inhibitors / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D013379:Substrate Specificity
D009124:Muscle Proteins; D011480:Protease Inhibitors; D010447:Peptide Hydrolases; D002154:Calpain; D020782:Matrix Metalloproteinases; D046988:Proteasome Endopeptidase Complex