p21-activated kinase 1 (PAK1) as a therapeutic target for cardiotoxicity

The p21-activated kinase 1 (PAK1), an effector protein of the small G protein Rac and cell division cycle protein 42 (Cdc42), is highly expressed in cardiac tissue. Although a large number of studies have explored the molecular basis and biological function of PAK1, research on PAK1 as a therapeutic target for cardiotoxicity remains in a stage of continuous innovation, and further clarification of its role in cardiotoxicity is required. In this review, we examine the important role of PAK1 in the programmed death (apoptosis, autophagy, and pyroptosis) of cardiomyocytes, and its involvement in oxidative stress and inflammatory responses, which are based on mitochondrial dysfunction and calcium homeostasis imbalance. We also summarize the related signaling pathways through which PAK1 may cause oxidative stress and inflammatory response in cardiotoxicity, and discuss the PAK1-mediated contributions of the gut microbiome and micro RNAs to cardiotoxicity. We propose that PAK1 holds great promise for novel therapeutic strategies to facilitate improvements in the treatment of complex and diverse cardiovascular diseases.

Automated summary

In this review, the importance of PAK1 in cardiac diseases, especially in the regulation of programmed cell death, oxidative stress, and inflammatory responses of cardiomyocytes, is discussed. The association of PAK1 with the gut microbiome and microRNAs in cardiotoxicity is also introduced.