VEGF-B/NRP1 Signaling Modulates Mitochondrial Homeostasis and Cardiac Function After Myocardial Infarction DOI Creative Commons

Sai Manasa Varanasi,

Ankit Sabharwal,

Riya Kar

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 20, 2025

Abstract Background Myocardial infarction (MI) remains a leading cause of mortality worldwide. Recent studies suggest cardioprotective role for vascular endothelial growth factor-B (VEGF-B) in MI. However, the molecular mechanisms VEGF-B-mediated signaling via its co-receptor Neuropilin-1 (NRP1) MI are poorly understood. In this study, we investigated intricate involving VEGF-B and NRP1 cardiomyocytes (CMs) using ischemic injury as model And secondly, further validated protective VEFG-B heart disease, shedding light on their roles not only cardiac function but also therapeutic potential. Methods utilized both vitro vivo approaches to elucidate how it manifests mitochondrial functions regeneration following injury. We used two different cardiomyocyte cell lines, H9c2 (rat ventricular cardiomyocytes) HL-1 (mouse cardiomyocytes), induced hypoxia conditions, either 1% oxygen or 200µM cobalt chloride (CoCl 2 ) mimic myocardial infarction-induced heart. addition, developed novel heat shock inducible zebrafish cardiomyocyte-specific overexpression system examine . Results Our findings indicate that predominantly expressed tissue compared other tissues, expression is altered response hypoxia/ischemic results demonstrate treatment prior enhances survival, while knockdown abolishes effect, highlighting prominent cardio protection. Furthermore, found promotes survival by improving function, evidenced reduced oxidative stress ROS accumulation, decreased stress, preserved membrane potential, increased ATP levels. Lastly, our transgenic model, demonstrated protects from an NRP1-dependent manner. Conclusion study has uncovered important VEGF-B-NRP1 axis mediated beneficial CMs. Importantly, against Novelty Significance What Is Known? dysfunction, death, adverse remodeling. Vascular Endothelial Growth Factor B traditionally associated with metabolism, biology, particularly angiogenesis lipid metabolism. The neurophilin-1 receptor, VEGF-B, implicated pathways. Emerging evidence suggests may influence integrity under conditions. New Information Does This Article Contribute? exerts effect mitocondria preserving reducing stress. receptor key mediator modulates homeostasis cardiomyocytes. can attenuate apoptosis enhance bioenergetics post-MI, suggesting mechanism. Clinical Implication: These strategies aimed at enhancing VEGF-B/NRP1 improve recovery after MI, offering avenue limiting failure progression disease.

Language: Английский

VEGF-B/NRP1 Signaling Modulates Mitochondrial Homeostasis and Cardiac Function After Myocardial Infarction DOI Creative Commons

Sai Manasa Varanasi,

Ankit Sabharwal,

Riya Kar

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 20, 2025

Abstract Background Myocardial infarction (MI) remains a leading cause of mortality worldwide. Recent studies suggest cardioprotective role for vascular endothelial growth factor-B (VEGF-B) in MI. However, the molecular mechanisms VEGF-B-mediated signaling via its co-receptor Neuropilin-1 (NRP1) MI are poorly understood. In this study, we investigated intricate involving VEGF-B and NRP1 cardiomyocytes (CMs) using ischemic injury as model And secondly, further validated protective VEFG-B heart disease, shedding light on their roles not only cardiac function but also therapeutic potential. Methods utilized both vitro vivo approaches to elucidate how it manifests mitochondrial functions regeneration following injury. We used two different cardiomyocyte cell lines, H9c2 (rat ventricular cardiomyocytes) HL-1 (mouse cardiomyocytes), induced hypoxia conditions, either 1% oxygen or 200µM cobalt chloride (CoCl 2 ) mimic myocardial infarction-induced heart. addition, developed novel heat shock inducible zebrafish cardiomyocyte-specific overexpression system examine . Results Our findings indicate that predominantly expressed tissue compared other tissues, expression is altered response hypoxia/ischemic results demonstrate treatment prior enhances survival, while knockdown abolishes effect, highlighting prominent cardio protection. Furthermore, found promotes survival by improving function, evidenced reduced oxidative stress ROS accumulation, decreased stress, preserved membrane potential, increased ATP levels. Lastly, our transgenic model, demonstrated protects from an NRP1-dependent manner. Conclusion study has uncovered important VEGF-B-NRP1 axis mediated beneficial CMs. Importantly, against Novelty Significance What Is Known? dysfunction, death, adverse remodeling. Vascular Endothelial Growth Factor B traditionally associated with metabolism, biology, particularly angiogenesis lipid metabolism. The neurophilin-1 receptor, VEGF-B, implicated pathways. Emerging evidence suggests may influence integrity under conditions. New Information Does This Article Contribute? exerts effect mitocondria preserving reducing stress. receptor key mediator modulates homeostasis cardiomyocytes. can attenuate apoptosis enhance bioenergetics post-MI, suggesting mechanism. Clinical Implication: These strategies aimed at enhancing VEGF-B/NRP1 improve recovery after MI, offering avenue limiting failure progression disease.

Language: Английский

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