The National Heart, Lung, and Blood Institute (NHLBI) awarded a $634,183 Project Grant (CFDA 93.837 - Cardiovascular Diseases Research) to Loyola University of Chicago's Health Sciences Campus to investigate the role of intersubunit cross-linking in ryanodine receptor (RyR) dysfunction during oxidative stress and myocardial infarction. The key goals are to define the molecular mechanisms by which oxidative stress-induced RyR cross-linking leads to calcium dysregulation and contractile dysfunction, and to evaluate whether pharmacological interventions targeting the cross-linking region can mitigate these effects. The project will utilize a transgenic mouse model with a RyR2 mutation that protects the channel from cross-linking. Findings may inform the development of new therapeutic strategies to improve calcium homeostasis and cardiac function in ischemic heart disease.
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