Joseph Fomusi Ndisang
University of Saskatchewan, Canada
Title: Hemeoxygenase ameliorates diabetic cardiomyopathy by potentiating electrocardiographic and hemodynamic parameters in obese Zucker rats
Biography
Biography: Joseph Fomusi Ndisang
Abstract
Deregulated insulin signaling is associated with progressive alterations in cardiac structure and function. We investigated the effects of the heme-oxygenase (HO) inducer, hemin, on cardiac dysfunction in obese Zucker rats, a model characterized by impaired insulin signaling. Administering hemin to obese Zucker rats enhanced insulin sensitivity and potentiated important components of insulin signal transduction pathway including IRS-1, PI3K and GLUT4. These were associated with the amelioration of several hemodynamic parameters including mean arterial pressure, arterial systolic pressure, +dP/dt and arterial diastolic pressure as well as electrocardiographic parameters related to the performance of the cardiac conduction system such as the PR-interval, QRS-duration, ST-segment and QT interval. Furthermore, hemin reduced LV-hypertrophy, abated diastolic/systolic LV-wall thickness, abolished cardiac fibrosis, suppressed inflammatory/oxidative mediators and attenuated extracellular matrix/pro-fibrotic proteins, whereas treatment with HO-blocker, stannous-mesoporphyrin, abolished the effects of hemin. We conclude that up-regulating the HO system with hemin improved altered cardiac structure and function in obese Zucker rats by attenuating inflammatory/oxidative insults, suppressing extracellular-matrix/profibrotic, while concomitantly potentiating insulin signaling and glucose metabolism.
