Grape seed proanthocyanidin reverses pulmonary vascular remodeling in monocrotaline-induced pulmonary arterial hypertension by down-regulating HSP70

Heat shock protein 70 (HSP70) is a molecular chaperone which has a low content in cytoplasm under normal physiological conditions. A higher intracytoplasmic HSP70 level can be observed in pulmonary arterial smooth muscle cell (PASMC) in pulmonary arterial hypertension (PAH), and this up-regulation can promote pho-IκBα expression, which is an NF-κB signaling pathway inhibitor. NF-κB signaling pathway up-regulation can promote PASMC proliferation and pulmonary vascular remodeling in PAH, resulting in elevation of pulmonary pressure and the subsequent right heart failure caused by right ventricular hypertrophy. Grape seed proanthocyanidin (GSP) is effective in vascular protection and several tumor treatments, and its effect on PAH treatment remains to be elucidated. In this study, we made observations and contrasts in monocrotaline(MCT) -induced PAH rats, and found decrease in mPAP, PVR and RVHI after GSP administration. Our study also proved GSP's effect on down-regulating the intracytoplasmic HSP70 content both in cellular and animal levels. The results indicate a possible mechanism of GSP reversing pulmonary vascular remodeling by down-regulating HSP70, and this change may influence pho-IκBα expression. Therefore, inhibition of NF-κB signaling pathway caused by GSP can lead to inhibition of PASMC proliferation in PAH.