Academic Journal
MK2‐Deficient Mice Are Bradycardic and Display Delayed Hypertrophic Remodeling in Response to a Chronic Increase in Afterload
| العنوان: | MK2‐Deficient Mice Are Bradycardic and Display Delayed Hypertrophic Remodeling in Response to a Chronic Increase in Afterload |
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| المؤلفون: | Matthieu Ruiz, Maya Khairallah, Dharmendra Dingar, George Vaniotis, Ramzi J. Khairallah, Benjamin Lauzier, Simon Thibault, Joëlle Trépanier, Yanfen Shi, Annie Douillette, Bahira Hussein, Sherin Ali Nawaito, Pramod Sahadevan, Albert Nguyen, Fatiha Sahmi, Marc‐Antoine Gillis, Martin G. Sirois, Matthias Gaestel, William C. Stanley, Céline Fiset, Jean‐Claude Tardif, Bruce G. Allen |
| المصدر: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, Vol 10, Iss 4 (2021) |
| بيانات النشر: | Wiley |
| سنة النشر: | 2021 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | bradycardia, cardiac remodeling, mitochondrial permeability transition pore, MK2, p38 MAPK, Diseases of the circulatory (Cardiovascular) system, RC666-701 |
| الوصف: | Background 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2047-9980 |
| Relation: | https://doaj.org/toc/2047-9980; https://doaj.org/article/f621d6d646c848bc8cfc1f57645591d9 |
| DOI: | 10.1161/JAHA.120.017791 |
| الاتاحة: | https://doi.org/10.1161/JAHA.120.017791 https://doaj.org/article/f621d6d646c848bc8cfc1f57645591d9 |
| رقم الانضمام: | edsbas.922DD26A |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20479980 |
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| DOI: | 10.1161/JAHA.120.017791 |