| Popis: |
It is well known that cardiac dysfunction in ischemic heart disease is associated with myocardial cell damage, apoptosis and activation of proteolytic enzymes including matrix metalloproteases (MMPs), cathepsin, calpains and caspases. These alterations due to ischemia-reperfusion (I/R) injury are mainly elicited by the occurrence of oxidative stress and the development of intracellular Ca2+-overload in the heart. Depression in the activities of endogenous inhibitors such as tissue inhibitors of metalloproteases increases the activity of MMPs whereas that of calpastatin augments the activity of calpains. Endothelial dysfunction associated with depressed formation of nitric oxide (NO) due to I/R injury has also been shown to increase the activity of calpain. While the activation of MMPs and cathepsin is mainly focused with the degradation of extracellular matrix proteins, the activation of calpain and MMP-2 has been reported to degrade sarcolemmal, sarcoplasmic reticular, mitochondrial and myofibrillar proteins. The activation of caspases has also been demonstrated to induce apoptosis in the ischemic-reperfused heart. These defects in the structure and function of subcellular organelles induced by protease activation are suggested to result in contractile abnormalities in the heart due to I/R injury. |
