DEPENDENCE OF DISORDERS OF ENERGY METABOLISM OF THE MYOCARDIUM ON THE LEVEL OF MATRIX METALLOPROTEINASE IN PATIENTS WITH METABOLIC SYNDROME
O.M. Kovalyova, Ye.O. Bolokadze
50 patients with metabolic syndrome and 20 practically healthy people were been examined. They underwent anthropometry and echocardiography. Plasma levels of proform of matrix metalloproteinase-1, insulin, glucose, MB-isoenzyme of creatine phosphokinase, pyruvate, lactate and lipid spectrum have been established. Close positive correlations between plasma levels of proMMP-1 and indices of energy metabolism have been established in patients with metabolic syndrome. Matrix metalloproteinase influences not only the condition of extracellular matrix but also the efficiency of different elements of energy-supply of the myocardium in patients with metabolic syndrome
Key words: matrix metalloproteinase, energy metabolism, remodeling of the myocardium of the left ventricle, extracellular matrix, metabolic syndrome.
For many years processes of energy-supply of the myocardium in different pathological conditions have been the subject of significant scientific discussions. It is known that myocardial contractility directly depends on the energy of phosphate bindings represented by adenosine triphosphate (ATP) and phosphocreatine (PC) [1-4]. For a long time PC has been considered a so-called energy buffer used in case of increase of muscular exercise. It was assumed that creatine phosphokinase (CPK) reactions were equilibrious to cytoplasmic ATP and intracellular energy transport was a passive diffusion of ATP from mitochondria till the place of its use in myofibrillas and in membranous ATP reactions [2,3]. During further study of CPK system its most active role in muscular cells due to heterogenic distribution of different CPK isoenzymes was discovered. In the myocardium about 30-40% of general CPK activity is localized in mitochondria, 40-50% - in cytoplasm and approximately 20% is related to myofibrillas, membrane of sarcoplasmic reticulum and sarcolemmatic cell membrane. In mitochondria CPK is localized on the outer side of the internal membrane and in presence of creatine it synthesizes PC from mitochondrial ATP . It was supposed and later proved with physiological tests that there was close connection between CPK system and adenine nucleotide translocase due to which end product of mitochondrial reactions of energy generation in presence of kreatine was PC, not ATP which, after diffusion in myoplasm, was used by CPK isoenzymes in myofibrillas and on cellular and subcellular non-mitochondrial membranes for regeneration of ATP from ADP. In myocardial cells not the whole ATP cell reserve but only its part, localized near active centres of the corresponding ATP phases, is available for emergency usage in reactions of contractility and ion transportation. This local ATP fund directly depends on CPK and can constantly regenerate thanks to PC due to connection between ATP and CPK reactions in all cellular structures where processes of ATP energy utilization take place. It is necessary to point out that mechanisms of CPK functioning in cytosol and mitochondria are different. In cytoplasm, where soluble CPK is located, there is excess of CPK relatively to the speed of glycolysis and it functions in semi-uniform condition. In homogeneous environment CPK reaction is sensitive to PC inhibition. Thanks to specific localization of CPK and close functional association with ATP-ADP translocase, direct CPK reaction in mitochondria is accelerated due to predominant use of mitochondrial ATP. Hereby CPK can function at the speed close to maximum, at low ATP concentration in the environment. This association enables lower degree of inhibition of PC creatine kinase.