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Abstract: FR-PO520

PPARγ Mediates Impaired Circadian Rhythmicity of Human Vascular Smooth Muscle Cells Cultured Under High Phosphate Environment

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Wang, Ningning, Department of Nephrology,The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
  • Wang, Qingting, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
  • Cui, Ying, Department of Nephrology,The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
Background

The onset of cardiovascular disease (CVD) in chronic kidney disease(CKD) patients often vary by time-of-day. Peroxisome proliferator-activated receptor γ (PPARγ) has been confirmed to play an important role in vascular smooth muscle cells (VSMC) by acting as a peripheral factor participating in regulation of cardiovascular circadian rhythms. It has been reported that hyperphosphatemia plays a vital role in abnormal cardiovascular circadian rhythms. Here we aim to investigate the role of PPARγ in the biorhythm regulation of human aortic vascular smooth muscle cells (HASMCs) under high phosphate environment in vitro.

Methods


The HASMCs were divided into (1) normal control group (1.0 mmol/L phosphorus), (2) high phosphorus group (2.5 mmol/L phosphorus), (3)PPARγ activator rosiglitazone group (10 μmol/L), and (4) high phosphorus(2.5 mmol/L phosphorus) + rosiglitazone group (10 μmol/L) (n=3). The timing of the beginning stimulated was counted as time 0. Thereafter, cells were collected every 4 hours for a total of 28 hours. The mRNA expressions of PPARγ, Bmal1, Per2 and Rev-erbα in different groups of cells at different time points were detected by quantitative polymerase chain reaction (qRT-PCR).

Results


The mRNA expressions of PPARγ and clock genes Bmal1, Per2, Rev-erbα showed circadian rhythm in control group of HASMCs. A high-phosphorus environment could inhibit the expression of above genes, thereby destroying the normal biorhythm of HASMCs. After activating PPARγ by rosiglitazone, the expression of clock genes were up-regulated, and the inhibited biorhythm of HASMCs by high-phosphorus environment could be reversed(Fig1).

Conclusion


Expression of PPARγ and clock genes Bmal1, Per2, Rev-erbα in HASMCs has circadian rhythm. High phosphorus environment destroys their normal biological rhythms by inhibiting PPARγ. We uncovered a vital role of PPARγ in vascular rhythms disorders under high phosphate environment, suggesting the new treatment target of CVD in CKD patients.

Funding

  • Government Support - Non-U.S.