A novel therapeutic target for treating heart disease
Heart disease is the number one cause of death in the United States. In Maryland alone, almost 30% of total deaths were due to heart disease in 2007. After a heart attack, the heart heals by scarring, and this leaves the heart prone o further heart attacks and heart failure. Myofibroblasts, cells that specialize in healing the wounded tissue through contraction and scar formation, become activated after the heart has been injured and have been shown to further disrupt the heart’s function. Because myofibroblasts are contractile and able to relay signals through mechanical coupling, I tested the novel hypothesis that myofibroblast contraction can influence cardiomyocyte, the working heart cell, electrical activity via intercellular mechanical coupling. Particularly, the role of mechanoelectric feedback, which is the modulation of electrical activity by mechanical activity, was examined in monolayers of co-cultured myofibroblasts and neonatal rat cardiomyocytes by inhibiting myofibroblast contraction and blocking mechanosensitive channels, ion channels that open in response to mechanical activation. Management of injured heart tissue currently includes pharmacologic therapies to limit adverse remodeling; however, these therapies often have detrimental systemic effects. Mechanosensitive channel blockers or myofibroblast-specific contraction inhibitors may provide a means to reduce the incidence of arrhythmias (disorders of normal heart rhythm). General knowledge of mechanoelectric coupling between myofibroblasts and cardiomyocytes may be an unrecognized mechanism for arrhythmia that could spur new forms of therapy.