{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:23:12Z","timestamp":1792794192914,"version":"4.5.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T00:00:00Z","timestamp":1655769600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Start-up Foundation of Guangzhou National Laboratory","id":[{"id":"https:\/\/ror.org\/03ybmxt82","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Medical Research Fund of Guangdong Province","award":["A2020630)"],"award-info":[{"award-number":["A2020630)"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["Grant No. 81970250"],"award-info":[{"award-number":["Grant No. 81970250"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Science Foundation of Guangdong Province","award":["Grant No. 2022A1515012310 and Grant No. 2021A1515010787"],"award-info":[{"award-number":["Grant No. 2022A1515012310 and Grant No. 2021A1515010787"]}]},{"name":"Shenzhen Key Laboratory of Metabolism and Cardiovascular Homeostasis","award":["Grant No. ZDSYS20190902092903237"],"award-info":[{"award-number":["Grant No. ZDSYS20190902092903237"]}]},{"name":"Basic Research Foundation of Shenzhen","award":["JCYJ20210324094006018 and JCYJ20180508152222104"],"award-info":[{"award-number":["JCYJ20210324094006018 and JCYJ20180508152222104"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Aging impairs cardiac function and increases susceptibility to myocardial ischaemic injury. Cardiac myosin light chain kinase (MLCK3) phosphorylates cardiac myosin regulatory light chain (MLC2), controlling sarcomere organization and cardiomyocyte contraction. Dysregulation of MLCK3 and phosphorylated MLC2 (p-MLC2) contributes to heart failure after myocardial infarction (MI). We aimed at exploring how the MLCK3\u2013p-MLC2 axis changes in aging hearts post MI and at investigating the underlying regulatory mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We generated adult (3 months) and aged (30 months) MI mouse models to compare their cardiac performance, and then detected MLCK3 expression and MLC2 activity. Aging increased the size of MI-induced infarctions and promoted cardiac contractile dysfunction. Furthermore, MLCK3 expression and MLC2 activity increased in adult hearts after MI, but not in aged hearts. miR-146a was found consistently increased in adult and aged hearts post MI. Mechanistic analyses performed in vitro demonstrated that miR-146a-5p down-regulated matrix metalloprotease (MMP)2\/16 expression in cardiomyocytes. This down-regulation in turn increased MLCK3 expression and MLC2 activity. However, miR-146a-5p failed to regulate the MMP2\/16\u2013MLCK3\u2013p-MLC2 axis in senescent cardiomyocytes or in cardiac miR-146a conditional knockout mice, with the latter experiencing an exacerbated deterioration of cardiac function post MI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These results suggest that an increase of MLCK3 and p-MLC2 contents through decreasing MMP2\/16 by miR-146a-5p represents a compensatory mechanism that can protect cardiac contractile function after MI. Aging impairs this miR-146a-5p-regulated MMP2\/16\u2013MLCK3\u2013p-MLC2 contractile axis, leading to compromised contractile function and increased susceptibility to heart failure.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvac104","type":"journal-article","created":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T14:38:02Z","timestamp":1655822282000},"page":"786-801","source":"Crossref","is-referenced-by-count":20,"title":["Impaired regulation of MMP2\/16\u2013MLCK3 by miR-146a-5p increased susceptibility to myocardial ischaemic injury in aging mice"],"prefix":"10.1093","volume":"119","author":[{"given":"Ming","family":"Dong","sequence":"first","affiliation":[{"name":"Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Department of Pathophysiology, Shenzhen University Health Science Center , 1066 Xueyuan Avenue, Nanshan District, Shenzhen 518060 , China"},{"name":"Guangzhou Laboratory, Guangzhou , Guangdong Province, 510005 , 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