Inhibition of P21-activated Kinase 1 Promotes Vascular Smooth Muscle Cells Apoptosis Through Reduction of Phosphorylation of Bad.

P21-activated kinase 1 (Pak1) has an effect on cell apoptosis and has recently been reported to play an important role in various cardiovascular diseases, in which vascular smooth muscle cell (VSMC) apoptosis is a key process. Thus, we hypothesized that Pak1 may be a novel target to regulate VSMC behaviors. In the present study, we found that the expression of Pak1 was dramatically upregulated in vascular smooth muscle cells (VSMCs) on H2O2 administration and was dependent on stimulation time. Through a loss-of-function approach, Pak1 knockdown increased apoptosis of VSMCs, as tested by TUNEL (TdT-mediated dUTP Nick-End Labeling) immunofluorescence staining, whereas it inhibited the proliferation of VSMCs examined by EdU staining. Moreover, we also noticed that Pak1 silencing promoted the mRNA and protein levels of pro-apoptosis genes but decreased anti-apoptosis marker expression. Importantly, we showed that Pak1 knockdown reduced the phosphorylation of Bad. Moreover, increased Pak1 expression was also noticed in carotid arteries on the wire jury. Our study identified that Pak1 acted as a novel regulator of apoptosis of VSMCs partially through phosphorylation of Bad. © The Author(s) 2023. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Citation

Lin Jiao, Wenjuan Yi, Yu-Rong Chang, Wen-Lin Cheng, Jian-Lei Cao, Sheng-Ping Chao, Fang Zhao, Zhibing Lu. Inhibition of P21-activated Kinase 1 Promotes Vascular Smooth Muscle Cells Apoptosis Through Reduction of Phosphorylation of Bad. American journal of hypertension. 2024 Jan 01;37(1):46-52

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PMID: 36634025

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