Abstract: TH-PO0277
Oxalate-Induced Mitochondrial Dysfunction in CKD-Linked Cardiovascular Disease
Session Information
- Hypertension and CVD: Mechanisms
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1601 Hypertension and CVD: Basic
Authors
- Mishra, Rashmi, NYU Langone Health, New York, New York, United States
- Xiong, Xiaozhong, NYU Langone Health, New York, New York, United States
- Jaber, Karim, NYU Langone Health, New York, New York, United States
- Akosah, Yaw A., New York University College of Dentistry, New York, New York, United States
- Pavlov, Evgeny, New York University College of Dentistry, New York, New York, United States
- Fishman, Glenn I, NYU Langone Health, New York, New York, United States
- Nazzal, Lama, NYU Langone Health, New York, New York, United States
Background
Chronic kidney disease (CKD) affects over 850 million people worldwide and is strongly associated with an increased risk of cardiovascular complications. CKD leads to elevated systemic oxalate levels, which have been linked to disease progression, systemic inflammation, and cardiovascular complications. However, mechanism underlying oxalate-induced cardiotoxicity in CKD are not well understood. Our preliminary in vivo studies using a CKD mouse model showed that an oxalate-rich diet worsens cardiac hypertrophy and mitochondrial damage. This study aims to investigate the toxic effects of oxalate on cardiomyocytes in order to identify the molecular mechanisms causing oxalate-induced cardiotoxicity.
Methods
We cultured H9c2 rat cardiomyoblast cells with varying concentrations of sodium oxalate (NaOx) (50, 100, 200 µM) for up to 96 hours and assessed transcriptional changes using RNA sequencing and RT-qPCR. In addition, we evaluated cell proliferation, reactive oxygen species (ROS) production, ATP levels, mitochondrial respiration, and membrane potential.
Results
Gene expression analysis of RNA-seq data from NaOx-treated H9c2 cells revealed upregulation of cardiomyopathy-associated genes, including MAPK13, ACTC1, ADCY8, TNNC1/2 and LMNA. Pathway analysis highlighted significant dysregulation of oxidative phosphorylation, ATP synthesis, and electron transport chain pathways. RT-qPCR further confirmed that NaOx treatment led to downregulation of genes involved in oxidative phosphorylation, fatty-acid metabolism and cholesterol metabolism, alongside upregulation of mitophagy-related genes. Functionally, NaOx treatment increased ROS production and reduced ATP generation. Mitochondrial toxicity was confirmed by real-time respirometry showing diminished oxygen consumption rates and a loss of membrane potential.
Conclusion
Together, these findings indicate that oxalate induces mitochondrial toxicity and cellular stress in cardiomyocytes. Ongoing investigations aim to further elucidate the mechanisms of oxalate-induced cardiotoxicity and identify potential targets to mitigate CKD-associated cardiovascular complications.
Funding
- NIDDK Support