Key result
Activation of p21-activated kinases 1 and 2 (Pak1/2) presents a promising therapeutic strategy to mitigate disease progression in hypertrophic cardiomyopathy by targeting calcium handling and ER stress.
Why the study?
Despite advances in understanding the molecular genetic basis of HCM, there remains a lack of effective and specific treatments to prevent disease progression.
Targeting p21-activated kinases (Pak1/2) presents a promising therapeutic strategy to mitigate disease progression in hypertrophic cardiomyopathy by addressing dysfunctional calcium handling, mitochondrial impairment, and ER stress.
Hypothesis-generating for Pak1/2 activation in hypertrophic cardiomyopathy; should not yet change practice without prospective trials.
Expert review p21-Activated Kinases Present a New Drug Target for Hypertrophic Cardiomyopathy He Yu , and Lei Ming , * Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK * Correspondence: ming.lei@pharm.ox.ac.uk Received: 17 February 2023 Accepted: 26 March 2023 Published: 21 August 2023 Abstract: Hypertrophic cardiomyopathy (HCM), primarily involving mutations in sarcomeric proteins, is the most common form of inherited heart disease and a leading cause of sudden death in young adults and athletes. HCM patients present with cardiac hypertrophy, fibrosis, and diastolic dysfunction often in a progressive manner. Despite significant progress made in understanding the molecular genetic basis of HCM, there remains a lack of effective and specific treatment for preventing disease progression in HCM. This article first provides an overview of recent progress in understanding the pathogenic basis of disease progression in HCM, in particular dysfunctional calcium handling, mitochondrial impairment, and endoplasmic reticulum stress. This article then analyses the evidence for critical roles of the multifunctional enzymes P21-activated kinase-1 and 2 (Pak1/2) in the heart and our opinion on their therapeutic value as a promising druggable target in pathological hypertrophy and associated ventricular arrhythmias.
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He et al. (2023) conducted a review in Hypertrophic cardiomyopathy. Pak1/2 activation was evaluated. Activation of p21-activated kinases 1 and 2 (Pak1/2) presents a promising therapeutic strategy to mitigate disease progression in hypertrophic cardiomyopathy by targeting calcium handling and ER stress.
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