ArticleBiochimica et biophysica acta. Molecular basis of disease2020
Nicotinamide riboside kinase-2 alleviates ischemia-induced heart failure through P38 signaling.
Article in Biochimica et biophysica acta. Molecular basis of disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- Differential transcriptomic and metabolomic landscape between human hearts donated after cardiac vs brain death.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2026Article
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- GSK-3α regulates miRNAs associated with transcriptional and metabolic processes in human cardiomyocytes under hypoxia.The Biochemical journal · 2025Article
- The Role of NADAmerican journal of cardiovascular drugs : drugs, devices, and other interventions · 2025Review
- Emerging interactions between mitochondria and NADTrends in endocrinology and metabolism: TEM · 2025Review
- Pathobiochemistry of Aging and Neurodegeneration: Deregulation of NAD+ Metabolism in Brain Cells.Biomolecules · 2024Review
- MiR-21-3p inhibitor exerts myocardial protective effects by altering macrophage polarization state and reducing excessive mitophagy.Communications biology · 2024Article
- The activation of P38MAPK Signaling Pathway Impedes the Delivery of the Cx43 to the Intercalated Discs During Cardiac Ischemia-Reperfusion Injury.Journal of cardiovascular translational research · 2024Article
- Losmapimod ameliorates doxorubicin-induced cardiotoxicity through attenuating senescence and inflammatory pathways.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- Cardiac NADNature cardiovascular research · 2024Article
- Nicotinamide Mononucleotide Supplementation: Understanding Metabolic Variability and Clinical Implications.Metabolites · 2024Review
- NAD in pathological cardiac remodeling: Metabolic regulation and beyond.Biochimica et biophysica acta. Molecular basis of disease · 2024Review
- Nicotinamide Riboside, a Promising Vitamin BMolecules (Basel, Switzerland) · 2023Review
- Circulating H-FABP as a biomarker of frailty in patients with chronic heart failure.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Integrated bioinformatics analysis for identifying key genes and pathways in female and male patients with dilated cardiomyopathy.Scientific reports · 2023Article
- Article
- Post-myocardial infarction fibrosis: Pathophysiology, examination, and intervention.Frontiers in pharmacology · 2023Review
- Balancing NADCellular and molecular life sciences : CMLS · 2022Review
- Harnessing NADCurrent heart failure reports · 2022Review
- Therapeutic Potential of Emerging NAD+-Increasing Strategies for Cardiovascular Diseases.Antioxidants (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Nicotinamide riboside kinase-2 (NRK-2), a muscle-specific β1 integrin binding protein, predominantly expresses in skeletal muscle with a trace amount expressed in healthy cardiac tissue. NRK-2 expression dramatically increases in mouse and human ischemic heart however, the specific role of NRK-2 in the pathophysiology of ischemic cardiac diseases is unknown. We employed NRK2 knockout (KO) mice to identify the role of NRK-2 in ischemia-induced cardiac remodeling and dysfunction. Following myocardial infarction (MI), or sham surgeries, serial echocardiography was performed in the KO and littermate control mice. Cardiac contractile function rapidly declined and left ventricular interior dimension (LVID) was significantly increased in the ischemic KO vs. control mice at 2 weeks post-MI. An increase in mortality was observed in the KO vs. control group. The KO hearts displayed increased cardiac hypertrophy and heart failure reflected by morphometric analysis. Consistently, histological assessment revealed an extensive and thin scar and dilated LV chamber accompanied with elevated fibrosis in the KOs post-MI. Mechanistically, we observed that loss of NRK-2 enhanced p38α activation following ischemic injury. Consistently, ex vivo studies demonstrated that the gain of NRK-2 function suppresses the p38α as well as fibroblast activation (α-SMA expression) upon TGF-β stimulation, and limits cardiomyocytes death upon hypoxia/re‑oxygenation. Collectively our findings show, for the first time, that NRK-2 plays a critical role in heart failure progression following ischemic injury. NRK-2 deficiency promotes post-MI scar expansion, rapid LV chamber dilatation, cardiac dysfunction and fibrosis possibly due to increased p38α activation.
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