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Kidney Week

Abstract: SA-PO773

Histone Deacetylase 9 Contributes to Vascular Calcification in CKD

Session Information

  • Hypertension and CVD: Mechanisms
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

  • 1503 Hypertension and CVD: Mechanisms

Authors

  • Xiong, Lin, Sichuan Academy of Medical Sciences and Sichuan People's Hospital, Chengdu, Sichuan, China
  • Xiao, Qiong, Sichuan Academy of Medical Sciences and Sichuan People's Hospital, Chengdu, Sichuan, China
  • Rong, Chen, Sichuan Academy of Medical Sciences and Sichuan People's Hospital, Chengdu, Sichuan, China
  • Tang, Yun, Sichuan Academy of Medical Sciences and Sichuan People's Hospital, Chengdu, Sichuan, China
  • Wang, Li, Sichuan Academy of Medical Sciences and Sichuan People's Hospital, Chengdu, Sichuan, China
  • Li, Yi, Sichuan Academy of Medical Sciences and Sichuan People's Hospital, Chengdu, Sichuan, China
  • Li, Guisen, Sichuan Academy of Medical Sciences and Sichuan People's Hospital, Chengdu, Sichuan, China
Background

Vascular calcification (VC) is a serious complication of chronic kidney disease (CKD). Unfortunately, there is no effective therapy for VC beyond supportive care due to the complex pathogenesis of VC. Histone deacetylase 9 (HDAC9) could regulate the transdifferentiation of vascular smooth muscle cells in atherosclerotic aortic calcification. However, the role of HDAC9 in VC upon CKD is unclear. The purpose of this study was to investigate the role and mechanism of HDAC9 in VC upon CKD.

Methods

Rat aortic smooth muscle cells (RASMCs) were divided into control and calcification group. The calcification group was induced with β-glycerophosphate and CaCl2. RASMCs were incubated with Alizarin Red S stain to detect calcification. Real-time quantitative PCR (RT-PCR) and western blotting(WB) were utilized to detect the expression level of HDAC9. 30 male wild-type Wistar rats were randomly divided into six groups (n=5): 4- and 16-week control groups, and 4-, 8-, 12-, and 16-week VC groups. The VC model of CKD in rats was established by 5/6 nephrectomy combined with high phosphorus chow. Rat aortas were collected and stained with alizarin red to detect VC. Subsequently, the expressions of HDAC9 were detected by third generation sequencing and immunohistochemical staining.

Results

In vitro, alizarin red staining showed the RASMCs in the calcified group had more calcium salt deposition compared with the control group. Both WB and RT-PCR showed the expression of HDAC9 in calcified cells was increased. In vivo, alizarin red staining of the aorta showed the vascular calcium deposition in the calcification group was significantly higher than that in the control group. In the third-generation full length transcriptome sequencing of rat aorta, the RNA expression of HDAC9 in calcification group increased gradually from 4 weeks to 12 weeks, and was significantly higher than that in 4- and 16- week control groups; From 12 to 16 weeks, the RNA expression of HDAC9 began to decline, but it was still higher than that of the 4-week and 16-week control groups. Moreover, immunohistochemical staining also indicated the expression of HDAC9 in the aorta of the 12-week calcification group was significantly increased, relative to the 4- and 16- week control groups.

Conclusion

Histone deacetylase 9 could contribute to development of vascular calcification in chronic kidney disease.