Abstract 18822: Endoglin Selectively Modulates TRPC Expression in Response to Left or Right Ventricular Pressure Overload
Introduction: Endoglin is an accessory receptor for the cytokine transforming growth factor beta. Reduced endoglin activity limits cardiac fibrosis due to left ventricular (LV) pressure overload. Recently, we reported that reducing endoglin activity also limits upregulation of the profibrogenic transient receptor potential canonical channel 6 (TRPC6) in the right ventricle (RV) during pressure overload. Few studies have compared TRPC channel expression in the RV versus LV.
Hypothesis: We hypothesized that endoglin regulates TRPC upregulation in response to RV and LV pressure overload.
Methods: To explore a functional role for endoglin as a regulator of TRPC expression in response to RV or LV pressure overload, endoglin haploinsufficient (Eng+/-) and wild-type (Eng+/+) mice were exposed to thoracic aortic (TAC) or pulmonary arterial (PAC) constriction for 10 weeks. Biventricular tissue was then analyzed by real-time polymerase chain reaction.
Results: After TAC, LV levels of TPRC1 and 6 were increased in both Eng +/+ and Eng +/- mice compared to sham controls. LV levels of TRPC4 were increased in Eng +/+, not Eng +/- mice after TAC. After PAC, RV levels of TRPC1, 3, 4, and 6 were increased in Eng +/+ compared to sham controls. In contrast, chronic RV pressure overload did not increase RV levels of TRPC1, 3, 4, and 6 in Eng +/- mice compared to sham controls.
Conclusions: Pressure overload induces distinct profiles of TRPC expression in the RV and LV and these effects in the RV require full endoglin activity. Taken together, these data support that endoglin may be an important and novel target of therapy to modulate RV responses to injury.
Author Disclosures: K.J. Morine: None. V. Paruchuri: None. X. Qiao: None. D.T. Pham: None. G.S. Huggins: None. D. Denofrio: None. M.S. Kiernan: None. R. Karas: None. N.K. Kapur: Speakers Bureau; Modest; Maquet; Abiomed; Heartware. Consultant/Advisory Board; Modest; Thoratec; Abiomed; Cardiac Assist; Maquet. Research Grant; Significant; Cardiac Assist; Abiomed; Maquet.
- © 2014 by American Heart Association, Inc.