Abstract
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.
Publisher
Australia Academic Press Pty Ltd
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