ArticleCardiovascular diabetology2023
Endothelial MICU1 alleviates diabetic cardiomyopathy by attenuating nitrative stress-mediated cardiac microvascular injury.
Article in Cardiovascular diabetology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 50 citations in OpenAlex.
- USP33 alleviates FIS1-dependent mitochondrial fission and cardiac microvascular injury in diabetic cardiomyopathy via deubiquitinating and stabilizing ATG7.Cell death & disease · 2026Article
- YY1 nitration participates in DbCM cardiomyocyte lipotoxicity by inhibiting ANXA3-induced microlipophagy.Redox biology · 2026Article
- Mitochondrial Homeostasis in Diabetic Cardiomyopathy: From Dysfunction to Therapeutic Strategies.Antioxidants (Basel, Switzerland) · 2026Review
- The importance of mitochondria and mitochondrial calcium signaling in health and disease: an updated outlook on inflammation.Journal of translational medicine · 2026Review
- Long Non-Coding RNAs in Diabetic Cardiomyopathy: Potential Function as Biomarkers and Therapeutic Targets of Exercise Training.Journal of cardiovascular translational research · 2025Review
- Multimorbidity and animal models.Animal models and experimental medicine · 2025Review
- Farrerol ameliorates diabetic cardiomyopathy by inhibiting ferroptosisWorld journal of diabetes · 2025Article
- Article
- c-FLIP Protects Cardiac Microcirculation in Sepsis-Induced Myocardial Dysfunction Via FUNDC1-Mediated Regulation of Mitochondrial Autophagy.JACC. Basic to translational science · 2025Article
- Acid sphingomyelinase promotes diabetic cardiomyopathy via disruption of mitochondrial calcium homeostasis.Cardiovascular diabetology · 2025Article
- Endothelial MICU1 protects against vascular inflammation and atherosclerosis by inhibiting mitochondrial calcium uptake.The Journal of clinical investigation · 2025Article
- Mitochondrial calcium uniporter complex: An emerging therapeutic target for cardiovascular diseases (Review).International journal of molecular medicine · 2025Review
- Diabetic cardiomyopathy from a gut microbiota perspective: research progress and prospects.Frontiers in medicine · 2025Review
- Sirt1/Drp1 Pathway Reduces Microvascular Endothelial Cell Injury in Diabetic Pateints' Hearts by Inhibiting Excessive Mitochondrial Division.Current vascular pharmacology · 2025Article
- MCU genetically altered mice suggest how mitochondrial CaTrends in endocrinology and metabolism: TEM · 2024Review
- Therapeutic potential of finerenone for diabetic cardiomyopathy: focus on the mechanisms.Diabetology & metabolic syndrome · 2024Review
- Intermedin Alleviates Diabetic Cardiomyopathy by Up-Regulating CPT-1β through Activation of the Phosphatidyl Inositol 3 Kinase/Protein Kinase B Signaling Pathway.Pharmaceuticals (Basel, Switzerland) · 2024Article
- MICU1's calcium sensing beyond mitochondrial calcium uptake.Biochimica et biophysica acta. Molecular cell research · 2024Review
- Macrod1 suppresses diabetic cardiomyopathy via regulating PARP1-NADActa pharmacologica Sinica · 2024Article
- MAP4K4 exacerbates cardiac microvascular injury in diabetes by facilitating S-nitrosylation modification of Drp1.Cardiovascular diabetology · 2024Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMyocardial microvascular injury is the key event in early diabetic heart disease. The injury of myocardial microvascular endothelial cells (CMECs) is the main cause and trigger of myocardial microvascular disease. Mitochondrial calcium homeostasis plays an important role in maintaining the normal function, survival and death of endothelial cells. Considering that mitochondrial calcium uptake 1 (MICU1) is a key molecule in mitochondrial calcium regulation, this study aimed to investigate the role of MICU1 in CMECs and explore its underlying mechanisms.
methodsTo examine the role of endothelial MICU1 in diabetic cardiomyopathy (DCM), we used endothelial-specific MICU1
resultsHere, we found that MICU1 expression is decreased in CMECs of diabetic mice. Moreover, we demonstrated that endothelial cell MICU1 knockout exacerbated the levels of cardiac hypertrophy and interstitial myocardial fibrosis and led to a further reduction in left ventricular function in diabetic mice. Notably, we found that AAV9-MICU1 specifically upregulated the expression of MICU1 in CMECs of diabetic mice, which inhibited nitrification stress, inflammatory reaction, and apoptosis of the CMECs, ameliorated myocardial hypertrophy and fibrosis, and promoted cardiac function. Further mechanistic analysis suggested that MICU1 deficiency result in excessive mitochondrial calcium uptake and homeostasis imbalance which caused nitrification stress-induced endothelial damage and inflammation that disrupted myocardial microvascular endothelial barrier function and ultimately promoted DCM progression.
conclusionsOur findings demonstrate that MICU1 expression was downregulated in the CMECs of diabetic mice. Overexpression of endothelial MICU1 reduced nitrification stress induced apoptosis and inflammation by inhibiting mitochondrial calcium uptake, which improved myocardial microvascular function and inhibited DCM progression. Our findings suggest that endothelial MICU1 is a molecular intervention target for the potential treatment of DCM.
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