ArticleScience translational medicine2013
Inhibition of the cardiomyocyte-specific kinase TNNI3K limits oxidative stress, injury, and adverse remodeling in the ischemic heart.
Article in Science translational medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 70 citations in OpenAlex.
- High levels of the cardiomyocyte-specific kinase Tnni3k impair zebrafish heart regeneration by driving chronic myocardial inflammation.bioRxiv : the preprint server for biology · 2026Article
- Tnni3k Is Cardioprotective in Viral Myocarditis.Journal of cardiovascular development and disease · 2026Article
- An Exploratory Study of Kinase Activation Profiles in Hypoxic Human Cardiomyocytes Treated with Protective Extracellular Vesicles.Research square · 2026Article
- Cardiomyocyte maturation and proliferation is a flip coin.BMC cardiovascular disorders · 2025Review
- JAK2/STAT3/HMGCS2 signaling aggravates mitochondrial dysfunction and oxidative stress in hyperuricemia-induced cardiac dysfunction.Molecular medicine (Cambridge, Mass.) · 2025Article
- Validation of novel predictors for early detection of cancer therapeutics-related cardiac dysfunction.Future cardiology · 2025Article
- Musings on intrinsic cardiomyocyte cell cycle activity and myocardial regeneration.Journal of molecular and cellular cardiology · 2023Review
- Expression Levels of theInternational journal of molecular sciences · 2023Article
- Genetic Burden ofCirculation. Genomic and precision medicine · 2023Article
- Embryonic Hyperglycemia Disrupts Myocardial Growth, Morphological Development, and Cellular Organization: An In Vivo Experimental Study.Life (Basel, Switzerland) · 2023Article
- Cardiac Troponin I-Interacting Kinase Affects Cardiomyocyte S-Phase Activity but Not Cardiomyocyte Proliferation.Circulation · 2023Article
- Gene losses may contribute to subterranean adaptations in naked mole-rat and blind mole-rat.BMC biology · 2022Article
- Whole-Exome Sequencing Identifies a Novel Variant (c.1538T > C) ofFrontiers in cardiovascular medicine · 2022Article
- Cardiac Remodeling and Repair: Recent Approaches, Advancements, and Future Perspective.International journal of molecular sciences · 2021Review
- Gene Expression Profiling of Skeletal Muscles.Genes · 2021Article
- Synthesis and Evaluation of Novel 1,2,6-Thiadiazinone Kinase Inhibitors as Potent Inhibitors of Solid Tumors.Molecules (Basel, Switzerland) · 2021Article
- Pinocembrin ameliorates post-infarct heart failure through activation of Nrf2/HO-1 signaling pathway.Molecular medicine (Cambridge, Mass.) · 2021Article
- The Diverse Roles of TNNI3K in Cardiac Disease and Potential for Treatment.International journal of molecular sciences · 2021Review
- The prevalent I686T human variant and loss-of-function mutations in the cardiomyocyte-specific kinase gene TNNI3K cause adverse contractility and concentric remodeling in mice.Human molecular genetics · 2021Article
- Silencing Cardiac Troponin I-Interacting Kinase Reduces Lipopolysaccharide-Induced Sepsis-Induced Myocardial Dysfunction in Rat by Regulating Apoptosis-Related Proteins.BioMed research international · 2021Article
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15 authors at 1 institution in 1 country.
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Abstract
Percutaneous coronary intervention is first-line therapy for acute coronary syndromes (ACS) but can promote cardiomyocyte death and cardiac dysfunction via reperfusion injury, a phenomenon driven in large part by oxidative stress. Therapies to limit this progression have proven elusive, with no major classes of new agents since the development of anti-platelets/anti-thrombotics. We report that cardiac troponin I-interacting kinase (TNNI3K), a cardiomyocyte-specific kinase, promotes ischemia/reperfusion injury, oxidative stress, and myocyte death. TNNI3K-mediated injury occurs through increased mitochondrial superoxide production and impaired mitochondrial function and is largely dependent on p38 mitogen-activated protein kinase (MAPK) activation. We developed a series of small-molecule TNNI3K inhibitors that reduce mitochondrial-derived superoxide generation, p38 activation, and infarct size when delivered at reperfusion to mimic clinical intervention. TNNI3K inhibition also preserves cardiac function and limits chronic adverse remodeling. Our findings demonstrate that TNNI3K modulates reperfusion injury in the ischemic heart and is a tractable therapeutic target for ACS. Pharmacologic TNNI3K inhibition would be cardiac-selective, preventing potential adverse effects of systemic kinase inhibition.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.