SIR Medicine Investigation Abstract
DECREASED PHOSPHORYLATION OF THE MYOSIN LIGHT CHAIN 2V ISOFORM OCCURS WITH AGE AND PREDISPOSES THE HEART TO FAILURE
Presenter:
Manjari Ranganathan, Illinois Mathematics and Science Academy, 1500 W. Sullivan Road, Aurora, IL 60506
Mentor:
Dr. Paul H. Goldspink, University of Illinois at Chicago
Abstract:
Cardiovascular decline associated with aging results from decreased intrinsic myocyte contractility is caused by one or more of three changes: altered adrenergic nervous system function, impaired delivery of calcium to contractile elements in the muscle cells, and reduced myosin-ATPase activity. However, all these changes converge at the level of the sarcomeric proteins and ultimately alter their functional interactions. We have noted aging changes the composition and the phosphorylation level of many important regulatory myofibrillar proteins. This baselines our examination of the mechanical and biochemical properties of these aging hearts in response to increased hemodynamic stress to investigate temporal events that mark progression of disease. Events at 3 and 6-months are associated with compensatory mechanisms whereas events at 9 and 12-months demonstrate signs of failure. Myofibrillar protein composition is altered due to the re-expression of the fetal myosin isoforms (MLCa and b-MHC) in the ventricles of aging mice. The expression of the atrial MLC isoforms is associated with a loss of MLC-2 phosphorylation at 12-months as determined by Western blotting and 2-D electrophoresis. These data suggest that the propagation of cardiac disease in the aging heart is due, in part, to changes in myofibrillar protein composition and/or phosphorylation. The altered expression of the myosin isoforms with age may be benign but when coupled with activation of protein kinases, the altered phosphorylation substrate appears to change the regulatory balance of the myofibrils to depress the contractile properties of the heart.