title: Knockout of p21-activated kinase-1 attenuates exercise-induced cardiac remodelling through altered calcineurin signalling.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Physiology and Biophysics, Center for Cardiovascular Research, University of Illinois at Chicago, 835 S. Wolcott Ave-Rm. E202, Chicago, IL 60612, USA.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Davis
authors.affiliation: Department of Physiology and Biophysics, Center for Cardiovascular Research, University of Illinois at Chicago, 835 S. Wolcott Ave-Rm. E202, Chicago, IL 60612, USA.
authors.forename: Jillian N
authors.initials: JN
authors.lastname: Simon
authors.affiliation: Department of Physiology and Biophysics, Center for Cardiovascular Research, University of Illinois at Chicago, 835 S. Wolcott Ave-Rm. E202, Chicago, IL 60612, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Utter
authors.affiliation: Department of Physiology and Biophysics, Center for Cardiovascular Research, University of Illinois at Chicago, 835 S. Wolcott Ave-Rm. E202, Chicago, IL 60612, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Mungai
authors.affiliation: Department of Physiology and Biophysics, Center for Cardiovascular Research, University of Illinois at Chicago, 835 S. Wolcott Ave-Rm. E202, Chicago, IL 60612, USA.
authors.forename: Manuel G
authors.initials: MG
authors.lastname: Alvarez
authors.affiliation: Department of Physiology and Biophysics, Center for Cardiovascular Research, University of Illinois at Chicago, 835 S. Wolcott Ave-Rm. E202, Chicago, IL 60612, USA.
authors.forename: Shamim A K
authors.initials: SA
authors.lastname: Chowdhury
authors.affiliation: Department of Physiology and Biophysics, Center for Cardiovascular Research, University of Illinois at Chicago, 835 S. Wolcott Ave-Rm. E202, Chicago, IL 60612, USA.
authors.forename: Ahlke
authors.initials: A
authors.lastname: Heydemann
authors.affiliation: Department of Physiology and Biophysics, Center for Cardiovascular Research, University of Illinois at Chicago, 835 S. Wolcott Ave-Rm. E202, Chicago, IL 60612, USA.
authors.forename: Yunbo
authors.initials: Y
authors.lastname: Ke
authors.affiliation: Department of Physiology and Biophysics, Center for Cardiovascular Research, University of Illinois at Chicago, 835 S. Wolcott Ave-Rm. E202, Chicago, IL 60612, USA Department of Medicine, Section of Cardiology, Center for Cardiovascular Research, University of Illinois, Chicago, IL 60612, USA.
authors.forename: Beata M
authors.initials: BM
authors.lastname: Wolska
authors.affiliation: Department of Physiology and Biophysics, Center for Cardiovascular Research, University of Illinois at Chicago, 835 S. Wolcott Ave-Rm. E202, Chicago, IL 60612, USA solarorj@uic.edu.
authors.forename: R John
authors.initials: RJ
authors.lastname: Solaro
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D019703:Calcineurin / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D006332:Cardiomegaly / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D059267:Cardiomegaly, Exercise-Induced; D002352:Carrier Proteins / Q000378:metabolism; D017079:Exercise Tolerance; D055786:Gene Knockout Techniques; D005838:Genotype; D006439:Hemodynamics; D018345:Mice, Knockout; D009200:Myocardial Contraction; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D009210:Myofibrils / Q000201:enzymology; D010641:Phenotype; D010766:Phosphorylation; D005082:Physical Exertion; D012420:Running; D015398:Signal Transduction; D014335:Tropomyosin / Q000378:metabolism; D020107:Troponin T / Q000378:metabolism; D020257:Ventricular Remodeling; D054462:p21-Activated Kinases / Q000172:deficiency* / Q000235:genetics; D000099211:Phospholamban; D000099163:Myosin Binding Protein C
chemical_list: D019703:Calcineurin; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D014335:Tropomyosin; D020107:Troponin T; D054462:p21-Activated Kinases; D000099211:Phospholamban; D000099163:Myosin Binding Protein C; C515905:Pak1 protein, mouse
keywords: Cardiac function; Exercise; Physiological hypertrophy; Treadmill running