Knockout of p21-activated kinase-1 attenuates exercise-induced cardiac remodelling through altered calcineurin signalling. (13th October 2015)

• Record Type: Journal Article
• Authors: Davis, Robert T.; Simon, Jillian N.; Utter, Megan; Mungai, Paul; Alvarez, Manuel G.; Chowdhury, Shamim A.K.; Heydemann, Ahlke; Ke, Yunbo; Wolska, Beata M.; Solaro, R. John
• Is Part Of: Cardiovascular research. Volume 108:Number 3(2015)
• Page Start: 335
• Page End: 347
• Publication Date: 2015-10-13
• Subjects: Physiological hypertrophy -- Cardiac function -- Exercise -- Treadmill running; Cardiovascular system -- Diseases -- Periodicals; Cardiovascular system -- Periodicals; 616.1
• DOI: 10.1093/cvr/cvv234
• Languages: English
• ISSNs: 0008-6363

Abstract

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.