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- Title
Knockout of p21-activated kinase-1 attenuates exercise-induced cardiac remodelling through altered calcineurin signalling.
- Authors
Davis 3rd, Robert T.; Simon, Jillian N.; Utter, Megan; Mungai, Paul; Alvarez, Manuel G.; Chowdhury, Shamim A. K.; Heydemann, Ahlke; Yunbo Ke; Wolska, Beata M.; Solaro, R. John
- Abstract
Aims: 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. Methods and results: 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. Conclusions: 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.
- Subjects
PROTEIN kinases; EXERCISE physiology; VENTRICULAR remodeling; CALCINEURIN; CARDIOVASCULAR system physiology; INTRACELLULAR calcium
- Publication
Cardiovascular Research, 2015, Vol 108, Issue 3, p335
- ISSN
0008-6363
- Publication type
Article
- DOI
10.1093/cvr/cvv234