Abstract: PUB281
Cardiotoxic Effect of Oxalate on Mitochondrial Function in Cardiomyocytes
Session Information
Category: Hypertension and CVD
- 1601 Hypertension and CVD: Basic
Authors
- Shen, Alex, Leon H. Charney Division of Cardiology, New York University Grossman School of Medicine, New York, New York, United States
- Bu, Lei, Leon H. Charney Division of Cardiology, New York University Grossman School of Medicine, New York, New York, United States
- Xiong, Xiaozhong, Division of Nephrology, New York University Grossman School of Medicine, New York, New York, United States
- Akosah, Yaw A., Department of Molecular Pathobiology, New York University College of Dentistry, New York, New York, United States
- Liu, Fangyu, Leon H. Charney Division of Cardiology, New York University Grossman School of Medicine, New York, New York, United States
- Pavlov, Evgeny, Department of Molecular Pathobiology, New York University College of Dentistry, New York, New York, United States
- Nazzal, Lama, Division of Nephrology, New York University Grossman School of Medicine, New York, New York, United States
- Fishman, Glenn I, Leon H. Charney Division of Cardiology, New York University Grossman School of Medicine, New York, New York, United States
Background
Oxalate is a metabolic byproduct that accumulates in the plasma of patients with chronic kidney disease. Oxalate has been suggested to induce mitochondrial dysfunction, cardiac inflammation, and subsequent myocardium remodeling. However, the underlying mechanism of oxalate in relation to cardiomyocytes remain poorly understood.
Methods
Neonatal rat ventricular myocytes (NRVMs) were isolated on postnatal day 1 (n=20) using a Miltenyi isolation kit. Agilent Seahorse plates were seeded with 15K cells/well, treated for 16 hours with 0 uM, 50 uM, or 100 uM sodium oxalate (NaOX) in quadruplicate. Primaria plates were seeded at 0.8M cells/well, treated for 3, 6, 12, or 16 hours with 0 uM, 50 uM, or 100 uM NaOX in triplicate. RNA extraction for qPCR was performed according to manufacturer’s protocol.
Results
Oxalate treated NRVMs displayed metabolic dysfunction with a dose dependent decrease in oxygen consumption rate (OCR) at basal, ATP-linked, and maximal respiration states. We also observed a dose dependent decrease in expression of transcripts encoding electron transport chain (ETC) components (Cox7a2, Cox7b, Ndufa1). Nrf1, a key mitochondrial biogenesis transcription factor which regulates cytochrome C and oxidative phosphorylation, was also dose dependently decreased when exposed to oxalate. We further observed a time-dependent decrease in Ppara, a transcription factor involved in beta oxidation and energy homeostasis.
Conclusion
Oxalate dose-dependently influenced metabolic gene expression and mitochondrial function in NRVMs. These findings suggest that accumulation of oxalate in chronic kidney disease may contribute to cardiac dysfunction through mitochondrial dysfunction. The mechanisms through which oxalate leads to these pathologic changes require additional investigation.