ArticleAnnals of translational medicine2021
Constitutive activation of ERK1/2 signaling protects against myocardial ischemia via inhibition of mitochondrial fragmentation in the aging heart.
Article in Annals of translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- The MEK inhibitor trametinib incurs mitochondrial injury and induces innate immune responses in the mouse heart.Science advances · 2026Article
- Ambrisentan attenuates cisplatin-related mitochondrial dysfunction in the heart via regulation of p53 and NF-κB signaling.Scientific reports · 2026Article
- VEGF and the VEGFMolecular neurobiology · 2025Article
- Cardioprotective response of remote ischemic preconditioning: Revealing possible role of cannabinoid type 2 receptor and AMPK-mediated autophagy in rats.Journal of cardiovascular and thoracic research · 2025Article
- The MEK inhibitor trametinib incurs mitochondrial injury and induces innate immune responses in the mouse heart.bioRxiv : the preprint server for biology · 2025Article
- Cancer therapy-related cardiovascular aging: mechanisms, monitoring, and intervention strategies.Frontiers in cardiovascular medicine · 2025Review
- Ginsenoside Rg1 treats chronic heart failure by downregulating ERK1/2 protein phosphorylation.In vitro cellular & developmental biology. Animal · 2024Article
- MEK inhibitors: a promising targeted therapy for cardiovascular disease.Frontiers in cardiovascular medicine · 2024Review
- [Therapeutic mechanism ofNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- Integrated bioinformatics and machine learning algorithms reveal the critical cellular senescence-associated genes and immune infiltration in heart failure due to ischemic cardiomyopathy.Frontiers in immunology · 2023Article
- The Role of PKC-MAPK Signalling Pathways in the Development of Hyperglycemia-Induced Cardiovascular Complications.International journal of molecular sciences · 2022Review
- Bmi-1-RING1B prevents GATA4-dependent senescence-associated pathological cardiac hypertrophy by promoting autophagic degradation of GATA4.Clinical and translational medicine · 2022Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundStudies have shown that the ability of the myocardium to tolerate ischemia becomes significantly compromised with age. During ischemia, several endogenous protective signals are activated to protect the heart from injury, among which extracellular-signal regulated kinase (ERK) 1/2 signaling has been established as playing a pivotal role. However, in aging hearts, the activation of ERK1/2 is compromised. Mitogen-activated protein kinase/ERK kinase (MEK) is a major regulator of ERK1/2 signaling. In the present study, we investigated whether transduction of CaMEK, a constitutively activated MEK, using adeno-associated virus serotype 9 (AAV9) could protect the aging heart against ischemia.
methodsMyocardial ischemia models were established in aging mice and senescent cardiomyocytes, and AAV9-mediated delivery of CaMEK was applied. Echocardiography, fluorescent staining, transmission electron microscopy, flow cytometry, and immunoblotting were used to explore the effects of CaMEK and their underlying mechanism.
resultsAAV9-CaMEK activated ERK1/2 signaling and exerted cardioprotective effects against ischemia in aging hearts. Specifically, CaMEK transduction decreased dynamin-related protein-1 (Drp1) expression and phosphorylation at serine 616, resulting in improved mitochondrial morphology and function in aging ischemic hearts. Furthermore, CaMEK transduction exerted similar protective effects in senescent cardiomyocytes under hypoxia. Meanwhile, with the inhibition of ERK1/2 signaling in senescent cardiomyocytes under hypoxia, the opposite effects were observed, including an increase in mitochondrial fragmentation and aggravation of mitochondrial dysfunction and cell apoptosis.
conclusionsOur results suggested that AAV9-CaMEK alleviated ischemia-induced myocardium injury in the aging heart, at least in part, through inhibition of mitochondrial fragmentation. Therefore, AAV9-CaMEK is a potential intervention for prevention of ischemia-induced injury of the aging myocardium.
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