Nuclear receptor subfamily 4 group A member 1 promotes myocardial ischemia/reperfusion injury through inducing mitochondrial fission factor-mediated mitochondrial fragmentation and inhibiting FUN14 domain containing 1-depedent mitophagy

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(11), P. 4458 - 4475

Published: Jan. 1, 2024

This study investigated the mechanism by which NR4A1 regulates mitochondrial fission factor (Mff)-related and FUN14 domain 1 (FUNDC1)-mediated mitophagy following cardiac ischemia-reperfusion injury(I/R). Our findings showed that damage regulation was positively correlated with pathological pan-apoptosis of myocardial cell mitochondria. Compared wild-type mice (WT), NR4A1-knockout exhibited resistance to injury fission, characterized activation. Results increased expression level, activating mediated Mff restoring phenotype FUNDC1. The inactivation FUNDC1 phosphorylation could not mediate normalization in a timely manner, leading an excessive stress response unfolded proteins imbalance homeostasis. process disrupted quality control network, accumulation damaged mitochondria activation pan-apoptotic programs. data indicate is novel critical target I/R exertsand negative regulatory effects Mff-mediated mito-fission inhibiting FUNDC1-mediated mitophagy. Targeting crosstalk balance between NR4A1-Mff-FUNDC1 potential approach for treating I/R.

Language: Английский

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Elamipretide: A Review of Its Structure, Mechanism of Action, and Therapeutic Potential

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 944 - 944

Published: Jan. 23, 2025

Mitochondria serve an essential metabolic and energetic role in cellular activity, their dysfunction has been implicated a wide range of disorders, including cardiovascular conditions, neurodegenerative syndromes. Mitochondria-targeted therapies, such as Elamipretide (SS-31, MTP-131, Bendavia), have consequently emerged topic scientific clinical interest. unique structure allowing for uptake variety cell types highly selective mitochondrial targeting. This mitochondria-targeting tetrapeptide selectively binds cardiolipin (CL), lipid found the inner membrane, thus stabilizing cristae structure, reducing oxidative stress, enhancing adenosine triphosphate (ATP) production. Preclinical studies demonstrated protective restorative efficacy models heart failure, neurodegeneration, ischemia–reperfusion injury, syndromes, muscle atrophy weakness. Clinical trials PROGRESS-HF, TAZPOWER, MMPOWER-3, ReCLAIM elaborate on preclinical findings highlight significant therapeutic potential Elamipretide. Further research may expand its application to other diseases involving well investigate long-term safety drug. The following review synthesizes current knowledge mechanisms action, promising fitness, improving bioenergetics, minimizing stress.

Language: Английский

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Redox Homeostasis and Molecular Biomarkers in Precision Therapy for Cardiovascular Diseases

Antioxidants, Journal Year: 2024, Volume and Issue: 13(10), P. 1163 - 1163

Published: Sept. 25, 2024

Precision medicine is envisioned as the future of cardiovascular healthcare, offering a more tailored and effective method for managing diseases compared to traditional one-size-fits-all approaches. The complex role oxidative stress in chronic within framework precision was carefully explored, delving into cellular redox status its critical involvement pathophysiological complexity (CVDs). review outlines mechanisms reactive oxygen species generation function antioxidants maintaining balance. It emphasizes elevated concentrations observed heart failure their detrimental impact on health. Various sources ROS system are examined, including mitochondrial dysfunction, which contributes DNA degradation. article also addresses stress's myocardial remodeling, process pivotal progression diseases. By integrating these aspects, underscores importance homeostasis identifies molecular biomarkers that can enhance therapy CVDs. insights provided aim pave way targeted therapeutic strategies mitigate stress, thereby improving patient outcomes medicine.

Language: Английский

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Notoginsenoside R1 Attenuates H/R Injury in H9c2 Cells by Maintaining Mitochondrial Homeostasis

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(1), P. 44 - 44

Published: Jan. 10, 2025

Mitochondrial homeostasis is crucial for maintaining cellular energy production and preventing oxidative stress, which essential overall function longevity. damage dysfunction often occur concomitantly in myocardial ischemia-reperfusion injury (MIRI). Notoginsenoside R1 (NGR1), a unique saponin from the traditional Chinese medicine Panax notoginseng, has been shown to alleviate MIRI previous studies, though its precise mechanism remains unclear. This study aimed elucidate mechanisms of NGR1 mitochondrial hypoxia/reoxygenation (H/R) H9c2 cells. The results showed that pretreatment effectively increased cell survival rates post-H/R, reduced lactate dehydrogenase (LDH) leakage, mitigated damage. Further investigation into mitochondria revealed alleviated structural damage, improved membrane permeability transition pore (mPTP) persistence, prevented potential (Δψm) depolarization. Additionally, enhanced ATP levels, activity respiratory chain complexes I-V after H/R, excessive reactive oxygen species (mitoROS) production, thereby protecting function. analysis indicated upregulated expression biogenesis-related proteins (PGC-1α, Nrf1, Nrf2) fusion (Opa1, Mfn1, Mfn2), while downregulating fission (Fis1, Drp1) reducing autophagy (mitophagy) as well mitophagy-related (Pink1, Parkin, BNIP3) post-H/R. Therefore, this can maintain by regulating mitophagy, fission-fusion dynamics, biogenesis, alleviating H/R cardiomyocytes.

Language: Английский

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Piezo1 deletion mitigates diabetic cardiomyopathy by maintaining mitochondrial dynamics via ERK/Drp1 pathway

Cardiovascular Diabetology, Journal Year: 2025, Volume and Issue: 24(1)

Published: March 20, 2025

Increasing evidence highlights the critical role of Piezo1 in cardiovascular diseases, with its expression upregulated diabetic heart. However, involvement pathogenesis cardiomyopathy (DCM) remains unclear. This study aims to elucidate regulatory mitochondrial dynamics within context DCM and investigate underlying mechanisms. We constructed cardiac-specific knockout (Piezo1∆Myh6) mice. Type 1 diabetes was induced using streptozotocin (STZ) injection while type 2 established through a high-fat diet combined STZ. Echocardiography assessed left ventricular function, histological evaluations used HE Masson staining examine cardiac pathology Piezo1fl/fl controls, Piezo1∆Myh6 Mitochondrial function including oxygen species level, morphology, respiration rate were also assessed. Our findings revealed that myocardium mice high-glucose-treated cells. Cardiac-specific improved dysfunction ameliorated fibrosis Moreover, deficiency attenuated impairment. exhibited increased calpain activity excessive fission mediated by Drp1 obvious reduced fusion; however, restored levels dysfunction. These observations corroborated H9C2 cells neonatal mouse cardiomyocytes. phosphorylation ERK1/2 vivo vitro. or treatment inhibitor function. provides first is elevated modulation dynamics, which reversed deficiency. Thus, inhibition may provide promising therapeutic strategy for DCM. In cardiomyocytes mice, Ca2+ entry upregulates activity, phosphorylated level Drp1. Therefore, shown hearts. Whereas, cardiomyocyte-specific alleviates

Language: Английский

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Exercise and dietary interventions in the management of diabetic cardiomyopathy: mechanisms and implications

Cardiovascular Diabetology, Journal Year: 2025, Volume and Issue: 24(1)

Published: April 9, 2025

The global prevalence of diabetes is rapidly increasing, significantly raising the risk various cardiovascular diseases. Among these, diabetic cardiomyopathy (DCM) a distinct and critical complication characterized by ventricular hypertrophy impaired myocardial contractility, ultimately progressing to heart failure making it leading cause mortality among patients. Despite advances in pharmacological therapies, effectiveness managing cardiac dysfunction DCM remains challenging. Consequently, exploring additional therapeutic strategies for prevention treatment urgently needed. Beyond approaches, lifestyle modifications, particularly exercise dietary interventions, play fundamental role due their significant benefits This review synthesizes recent advancements field, elucidating underlying mechanisms through which interventions influence pathophysiology. By integrating these strategies, we aim facilitate development personalized regimens that effectively mitigate or prevent progression.

Language: Английский

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Impact of insulin resistance and microvascular ischemia on myocardial energy metabolism and cardiovascular function: pathophysiology and therapeutic approaches

Cardiovascular Endocrinology & Metabolism, Journal Year: 2025, Volume and Issue: 14(2)

Published: April 16, 2025

Insulin resistance (IR) and microvascular ischemia together result in cardiovascular dysfunction by impairing the heart’s energy balance. IR cardiomyocytes disrupts glucose metabolism, leading to deficits that can drive cardiac hypertrophy heart failure. Microvascular exacerbates these effects limiting oxygen nutrient delivery, intensifying oxidative stress, mitochondrial dysfunction, cell death. also reduces effectiveness of vasodilators like nitroglycerin sodium nitroprusside, exacerbating endothelial thus delivery during ischemia. This combination heightens risk left ventricular Understanding interactions is critical for developing targeted therapies improve outcomes patients with ischemic disease. study examines relationship between IR, ischemia, myocardial a focus on clinical management therapeutic strategies.

Language: Английский

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Advances in Understanding Diabetic Kidney Disease Progression and the Mechanisms of Acupuncture Intervention

International Journal of General Medicine, Journal Year: 2024, Volume and Issue: Volume 17, P. 5593 - 5609

Published: Nov. 1, 2024

Diabetic kidney disease (DKD) is a form of damage resulting from diabetes and represents common, severe complication the disease. Globally, DKD leading cause chronic (CKD). occurs in both type 1 2 patients, with early clinical manifestations including microalbuminuria hypertension. As condition progresses, symptoms such as massive proteinuria, hypoalbuminemia, edema may appear. The key to treating lies controlling blood glucose pressure, reducing slowing deterioration function. Acupuncture, traditional Chinese medicine treatment, has shown some therapeutic effects on through mechanisms regulating glucose, improving renal flow microcirculation, antioxidation anti-inflammation, modulating gut microbiota.

Language: Английский

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