Clinical & Experimental Cardiology
Open Access

p21-activated kinase 3 aggravates pathological cardiac hypertrophy in mice

Joint Conference on 17^th European Heart Disease and Heart Failure Congress and 2^nd International Conference on Cardiovascular Medicine and Cardiac Surgery

March 15-17, 2017 London, UK

Jun Xie

Nanjing Drum Tower Hospital, China

Posters & Accepted Abstracts: J Clin Exp Cardiolog

Abstract :

Background & Aim: p21-activated kinase 3 (PAK3) is the critical downstream molecular in Rho GTPase signaling, and involved in cell survival, proliferation and cytoskeleton remodeling. The PAK family is expressed in the heart, while the detail role of PAK3 in cardiac hypertrophy is little to know. Here, we designed this study to explore the effects of PAK3 in cardiac hypertrophy. Methods & Results: We observed the activation of PAK3 in failing human hearts, hypertrophic murine hearts and hypertrophic NRCMs. Then thoracic aortic constriction (TAC) was used to induce cardiac hypertrophy in PAK3 deficiency mice and wild-type control. PAK3 knockout mice displayed improved survival rate, relieved cardiac hypertrophy, well-preserved cardiac function, less fibrosis and decreased cardiomyocyte apoptosis compared with wild-type mice. In cell study, Ang II was used to induce NRCMs hypertrophy. The PAK3 and Raf1 were depressed by shRNAs and specific inhibitor. Cardiomyocyte hypertrophy was inhibited by selective knockdown of PAK3. Furthermore, the pro-hypertrophic effect of PAK3 was associated with activation of the Raf1-ERK1/2 signaling cascade. The rescue experiments revealed that the inactivation of Raf1-ERK1/2 pathway by pharmacological or RNAi rescued cardiac hypertrophy in cardiomyocytes with PAK3 overexpression. Conclusions: Here, we concluded that PAK3 was a novel hypertrophic regulator via the positive regulation of Raf1-ERK1/2 signaling in pathological cardiac hypertrophy.

Biography :

Email: darcy_pann@hotmail.com