Abstract 290: Cardiac Myocyte Gq Signaling Decreases Cardiac Function During Chronic High Blood Pressure Through Cardiac Remodeling
Chronic pressure overload and elevated levels of neurohormones initiate cardiac hypertrophy(HYP) and dysfunction. These neurohormones bind to Gq protein-coupled receptors which are an integral part of the cardiac HYP process. This study was designed to determine whether inhibiting Gq signaling in cardiac myocytes by expression of an inhibitory peptide (GqI) could decrease cardiac HYP and improve function following the 2 kidney, 1 clip (2K1C) model of hypertension (HBP).
Methods: GqI and control mice had 2K1C surgery and echo was performed basally and at 2, 4, and 8 weeks. Cross sectional area was measured in tissue sections and isolated myocytes were field stimulated at 0.5 Hz and cell volume calculated. RT profile arrays (Superarray) of extracellular(EC) genes were performed on ventricular tissue.
Results: GqI improved ejection fraction at 4(58.6±2.4% vs. 50.6±2.2%) and 8 weeks (53.2±2.4 vs. 43.8±2.0) following HBP, but did not decrease cardiac HYP. Improved cardiac function of GqI hearts was not due to decreases in the amount of cardiac myocyte HYP(cross sectional area and cell volume) or changes in the basal contractility of myocytes. Inhibiting Gq signaling attenuated the decrease in pAkt and also reversed the increased expression of at least six EC matrix genes (Adamts2, Adamts8, periostin, thrombospondin-1, tenascin C, MMP3) following hypertension.
Conclusions: These data suggest that cardiac myocyte Gq signaling plays a vital role in the development of cardiac HYP and function through regulation of the EC matrix. Furthermore, these data provide novel insight into the role of Gq signaling in communication between cardiac myocytes and non-myocytes of the heart.