Trépanier Joëlle, Nawaito Sherin A, Sahadevan Pramod, Sahmi Fatiha, Duquette Natacha, Gélinas Danielle, Gillis Marc-Antoine, Shi Yanfen, Torok Cynthia, Clavet-Lanthier Marie-Élaine, Gaestel Matthias, Sirois Martin G, Tardif Jean-Claude, Allen Bruce G
Montreal Heart Institute, Montréal, Québec, Canada.
Department of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, Québec, Canada.
Physiol Rep. 2025 Sep;13(18):e70558. doi: 10.14814/phy2.70558.
Altering inflammation can impact the recovering heart's structure and function following myocardial infarction (MI). MAP kinase-activated protein kinase 2 (MK2) regulates the stability of several pro-inflammatory cytokines. Hence, this study was to determine if MK2 deficiency impaired the inflammatory phase of post-MI wound repair. Myocardial infarctions were induced by permanent ligation of the left anterior descending coronary artery in 12-week-old male MK2 and MK2 mice. Five days post-MI, survival was 100% in MI-MK2 (n = 20) and 79% in MI-MK2 mice (n = 29; Mandel-Cox test: p < 0.05). Systolic and diastolic LV diameters were greater in MI-MK2 than MI-MK2 mice. Infiltration of neutrophils or monocytes did not differ significantly. Cytokine and chemokine transcripts were quantified in infarcted and non-infarcted LV tissue using qPCR arrays. Three days post-MI, Ifna2 was increased and Il16 was decreased in infarcted tissue from MK2 hearts, compared with infarcted MK2 tissue, whereas in the non-infarcted MK2 myocardium Il27 increased and Tnfsf11, Ccl3, and Il1rn were decreased. Five days post-MI, Ctf16 and Il10 increased in infarcted MK2 tissue whereas in the non-infarcted MK2 myocardium Ccl9, Nodal, and Xcl2 increased and Il15 decreased. These findings suggest MK2 deficiency is an advantage during the inflammatory phase of cardiac wound repair post-MI.
改变炎症反应会影响心肌梗死后恢复中心脏的结构和功能。丝裂原活化蛋白激酶激活的蛋白激酶2（MK2）调节多种促炎细胞因子的稳定性。因此，本研究旨在确定MK2缺乏是否会损害心肌梗死后伤口修复的炎症阶段。通过永久性结扎12周龄雄性MK2和MK2小鼠的左前降支冠状动脉诱导心肌梗死。心肌梗死后5天，MI-MK2组（n = 20）的存活率为100%，MI-MK2小鼠组（n = 29；Mandel-Cox检验：p < 0.05）的存活率为79%。MI-MK2小鼠的左心室收缩和舒张直径大于MI-MK2小鼠。中性粒细胞或单核细胞的浸润没有显著差异。使用qPCR阵列对梗死和未梗死的左心室组织中的细胞因子和趋化因子转录本进行定量。心肌梗死后3天，与梗死的MK2组织相比，MK2心脏梗死组织中的Ifna2增加，Il16减少，而在未梗死的MK2心肌中，Il27增加，Tnfsf11、Ccl3和Il1rn减少。心肌梗死后5天，梗死的MK2组织中Ctf16和Il10增加，而在未梗死的MK2心肌中，Ccl9、Nodal和Xcl2增加，Il15减少。这些发现表明，MK2缺乏在心肌梗死后心脏伤口修复的炎症阶段是一个优势。
