MOLECULAR-CHANGES OF TITIN IN LEFT-VENTRICULAR DYSFUNCTION AS A RESULT OF CHRONIC HIBERNATION

Cardiomyocytes of chronic hibernating myocardium are affected by parti al to complete loss of sarcomeres, accumulation of glycogen, adaptatio ns in size and shape of mitochondria, reorganisation of nuclear chroma tin and depletion of sarcoplasmic reticulum. The nature of these chang es, which from a purely morphologic viewpoint are akin to dedifferenti ation, needed further clarification at the molecular level, For this p urpose we have studied the expression and reorganization of titin, one of the earliest markers of cardiomyocyte differentiation. By use of m onoclonal antibodies, recognizing different epitopes distributed over the whole length of the titin molecule, we were able to detect changes in its molecular organization as a result of chronic hibernation, The epitopes of the titin molecule attached to the Z-disc and those prese nt close to the M-line remained detectable at all stages of hibernatio n, while epitopes at the A-I junction and parts of the myosin anchorin g region of the molecule became masked or were lost. A fragmented or p unctuated appearance of the titin staining pattern with antibodies to A-I junction related epitopes is found in cells which we consider to r epresent a more advanced stage of dedifferentiation. Changes in the di stribution of the titin molecule or its molecular environment in hiber nating myocardium resemble at least in part changes occurring during m uscle cell differentiation, although in reversed order.