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dc.contributor.authorRuiz, Matthieu
dc.contributor.authorKhairallah, Maya
dc.contributor.authorDingar, Dharmendra
dc.contributor.authorVaniotis, George
dc.contributor.authorKhairallah, Ramzi J
dc.contributor.authorLauzier, Benjamin
dc.contributor.authorThibault, Simon
dc.contributor.authorTrépanier, Joëlle
dc.contributor.authorShi, Yanfen
dc.contributor.authorDouillette, Annie
dc.contributor.authorHussein, Bahira
dc.contributor.authorNawaito, Sherin Ali
dc.contributor.authorSahadevan, Pramod
dc.contributor.authorNguyen, Albert
dc.contributor.authorSahmi, Fatiha
dc.contributor.authorGillis, Marc-Antoine
dc.contributor.authorSirois, Martin G
dc.contributor.authorGaestel, Matthias
dc.contributor.authorStanley, William C
dc.contributor.authorFiset, Céline
dc.contributor.authorTardif, Jean-Claude
dc.contributor.authorAllen, Bruce G
dc.date.accessioned2021-03-04T21:43:49Z
dc.date.available2021-03-04T21:43:49Z
dc.date.issued2021-02-03
dc.identifier.urihttp://hdl.handle.net/10713/14824
dc.description.abstractBackground Mitogen-activated protein kinase-activated protein kinase-2 (MK2) is a protein serine/threonine kinase activated by p38α/β. Herein, we examine the cardiac phenotype of pan MK2-null (MK2-/-) mice. Methods and Results Survival curves for male MK2+/+ and MK2-/- mice did not differ (Mantel-Cox test, P=0.580). At 12 weeks of age, MK2-/- mice exhibited normal systolic function along with signs of possible early diastolic dysfunction; however, aging was not associated with an abnormal reduction in diastolic function. Both R-R interval and P-R segment durations were prolonged in MK2-deficient mice. However, heart rates normalized when isolated hearts were perfused ex vivo in working mode. Ca2+ transients evoked by field stimulation or caffeine were similar in ventricular myocytes from MK2+/+ and MK2-/- mice. MK2-/- mice had lower body temperature and an age-dependent reduction in body weight. mRNA levels of key metabolic genes, including Ppargc1a, Acadm, Lipe, and Ucp3, were increased in hearts from MK2-/- mice. For equivalent respiration rates, mitochondria from MK2-/- hearts showed a significant decrease in Ca2+ sensitivity to mitochondrial permeability transition pore opening. Eight weeks of pressure overload increased left ventricular mass in MK2+/+ and MK2-/- mice; however, after 2 weeks the increase was significant in MK2+/+ but not MK2-/- mice. Finally, the pressure overload-induced decrease in systolic function was attenuated in MK2-/- mice 2 weeks, but not 8 weeks, after constriction of the transverse aorta. Conclusions Collectively, these results implicate MK2 in (1) autonomic regulation of heart rate, (2) cardiac mitochondrial function, and (3) the early stages of myocardial remodeling in response to chronic pressure overload.en_US
dc.description.urihttps://doi.org/10.1161/JAHA.120.017791en_US
dc.language.isoenen_US
dc.publisherAmerican Heart Association Inc.en_US
dc.relation.ispartofJournal of the American Heart Associationen_US
dc.subjectMK2en_US
dc.subjectbradycardiaen_US
dc.subjectcardiac remodelingen_US
dc.subjectmitochondrial permeability transition poreen_US
dc.subjectp38 MAPKen_US
dc.titleMK2-Deficient Mice Are Bradycardic and Display Delayed Hypertrophic Remodeling in Response to a Chronic Increase in Afterload.en_US
dc.typeArticleen_US
dc.identifier.doi10.1161/JAHA.120.017791
dc.identifier.pmid33533257
dc.source.volume10
dc.source.issue4
dc.source.beginpagee017791
dc.source.endpage
dc.source.countryEngland


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