Unraveling the role of LDHA and VEGFA in oxidative stress: A pathway to therapeutic interventions in cerebral aneurysms

Authors

  • Jiaying Wu Department of Neurology, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • Lixia Lu Department of Neurology, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai, China
  • Beibei Dai Department of Ultrasound, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
  • Aiyong Yu Department of Neurology, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

DOI:

https://doi.org/10.17305/bb.2024.10510

Keywords:

Cerebral aneurysms, LDHA, glycolysis, lactate metabolism, pathogenesis, therapeutic targets, blood vessels, enzyme, molecular mechanisms

Abstract

Cerebral aneurysms (CA) are critical conditions often associated with oxidative stress in vascular endothelial cells (VECs). The enzyme lactate dehydrogenase A (LDHA) plays a crucial role in glycolysis and lactate metabolism, processes implicated in the pathogenesis of aneurysms. Understanding these molecular mechanisms can inform the development of novel therapeutic targets. This study investigated the role of lactate metabolism and lactate-related genes, particularly LDHA and vascular endothelial growth factor A (VEGFA) genes, in VECs during oxidative stress. Using the GSE26969 dataset, we identified differential expression of lactate-related genes and performed functional enrichment analysis, revealing significant associations with glycolysis and lactate metabolic pathways. To induce oxidative stress, VECs were treated with H2O2, and the expression of LDHA and VEGFA was analyzed using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB) assays. Under oxygen-glucose deprivation/reperfusion (OGD/R) conditions, the effects of LDHA overexpression and VEGFA knockdown on cell viability and apoptosis were evaluated. Immunoprecipitation combined with western blotting was used to detect the lactylation status of LDHA following OGD/R stimulation and treatment with lactic acid (LA) and 2-deoxyglucose (2-DG). Our results indicated that oxidative stress modulates LDHA expression, glucose uptake, and lactate production, suggesting a metabolic shift towards glycolysis. LDHA overexpression improved cell survival and reduced apoptosis, while VEGFA knockdown had the opposite effect. Additionally, 2-DG treatment reduced LDHA lactylation and apoptosis. Our findings demonstrated that LDHA plays a critical role in the oxidative stress response of VECs, highlighting the potential therapeutic value of targeting glycolysis in CA. This study contributes to the understanding of metabolic adaptations in vascular pathologies and suggests new avenues for therapeutic intervention in CA management.

Citations

Downloads

Download data is not yet available.
Unraveling the role of LDHA and VEGFA in oxidative stress: A pathway to therapeutic interventions in cerebral aneurysms

Published

01-06-2024

Data Availability Statement

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Issue

Section

Translational and Clinical Research

Categories

How to Cite

1.
Unraveling the role of LDHA and VEGFA in oxidative stress: A pathway to therapeutic interventions in cerebral aneurysms. Biomol Biomed [Internet]. 2024 Jun. 1 [cited 2024 Jul. 24];. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/10510