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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, RESULTS. Meshes: Adaptation, Physiological, Animals, Calcineurin, Calcium-Binding Proteins, Cardiomegaly, Cardiomegaly, Exercise-Induced, Carrier Proteins, Exercise Tolerance, Gene Knockout Techniques, Genotype, Hemodynamics, Mice, Knockout, Myocardial Contraction, Myocardium, Myofibrils, Phenotype, Phosphorylation, Physical Exertion, Running, Signal Transduction, Tropomyosin, Troponin T, Ventricular Remodeling, p21-Activated Kinases.
user
Does knockout of p21-activated kinase-1 attenuate exercise-induced cardiac remodelling through altered calcineurin signalling? Context: Despite its known cardiovascular benefits, the intracellular signalling mechanisms underlying physiological cardiac growth remain poorly understood. Therefore, the purpose of this study was to investigate a novel role of p21-activated kinase-1 (Pak1) in the regulation of exercise-induced cardiac hypertrophy. Wild-type (WT) and Pak1 KO mice were subjected to 6 weeks of treadmill endurance exercise training (ex-training). Cardiac function was assessed via echocardiography, in situ haemodynamics, and the pCa-force relations in skinned fibre preparations at baseline and at the end of the training regimen. Post-translational modifications to the sarcomeric proteins and expression levels of calcium-regulating proteins were also assessed following ex-training. Heart weight/tibia length and echocardiography data revealed that there was marked hypertrophy following ex-training in the WT mice, which was not evident in the KO mice. Additionally, following ex-training, WT mice demonstrated an increase in cardiac contractility, myofilament calcium sensitivity, and phosphorylation of cardiac myosin-binding protein C, cardiac TnT, and tropomyosin compared with KO mice. With ex-training in WT mice, there were also increased protein levels of calcineurin and increased phosphorylation of phospholamban.
assistant
Our data suggest that Pak1 is essential for adaptive physiological cardiac remodelling and support previous evidence that demonstrates Pak1 signalling is important for cardiac growth and survival. Final Decision: yes