ArticleCardiovascular research2023
Impaired regulation of MMP2/16-MLCK3 by miR-146a-5p increased susceptibility to myocardial ischaemic injury in aging mice.
Article in Cardiovascular research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 14 citations in OpenAlex.
- Mapping the miRNA landscape of primitive macrophage extracellular vesicles highlights their pro-vasculogenic effects in engineered human cardiac tissue.APL bioengineering · 2026Article
- Evaluation of an experimental model of senescence SAMR1/SAMP8 for microRNA studies in acute myocardial infarction: role of sex and aging.Journal of physiology and biochemistry · 2026Article
- Harnessing the novel safeguarding role of Selenoprotein T in age-related myocardial left and right decline through the ferroptosis-mitochondrial axis.Journal of translational medicine · 2026Article
- Decoding noncoding RNAs in regulating cardiovascular aging and age-related conditions: the emerging landscape.Science China. Life sciences · 2026Review
- Cellular and molecular mechanisms underlying cardiovascular aging.Cellular & molecular biology letters · 2025Review
- Adipose-derived small extracellular vesicle miR-146a-5p targets Fbx32 to regulate mitochondrial autophagy and delay aging in skeletal muscle.Journal of nanobiotechnology · 2025Article
- The interplay of senescence and MMPs in myocardial infarction: implications for cardiac aging and therapeutics.Biogerontology · 2025Review
- Identification of Mitophagy-Related Genes and Analysis of Immune Infiltration in Atherosclerosis.Journal of inflammation research · 2025Article
- Impact of microRNAs on cardiovascular diseases and aging.The Journal of international medical research · 2024Review
- METTL14-mediated N6-methyladenosine modification induces the ferroptosis of hypoxia/reoxygenation-induced cardiomyocytes.Journal of cardiothoracic surgery · 2024Article
- M2 macrophage‑derived exosomes alleviate KCa3.1 channel expression in rapidly paced HL‑1 myocytes via the NF‑κB (p65)/STAT3 signaling pathway.Molecular medicine reports · 2024Article
- Cardioprotective effect of naringin against the ischemia/reperfusion injury of aged rats.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Identification of key biomarkers associated with immune cells infiltration for myocardial injury in dermatomyositis by integrated bioinformatics analysis.Arthritis research & therapy · 2023Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsAging 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-p-MLC2 axis changes in aging hearts post MI and at investigating the underlying regulatory mechanisms. METHODS AND
resultsWe 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-MLCK3-p-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.
conclusionThese 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-MLCK3-p-MLC2 contractile axis, leading to compromised contractile function and increased susceptibility to heart failure.
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