Abstract: FR-PO389
Histone Deacetylase 9 Contributes to Vascular Calcification in CKD
Session Information
- Hypertension and CVD: Basic
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1601 Hypertension and CVD: Basic
Authors
- Xiong, Lin, 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
- Wang, Li, 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 chronic kidney disease (CKD) complication. 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. This study aimed to investigate the role and mechanism of HDAC9 in VC upon CKD.
Methods
Rat aortic smooth muscle cells (RASMCs) were divided into the control and calcification groups. The calcification group was induced with β-glycerophosphate and CaCl2. RASMCs were incubated with Alizarin Red S stain to detect calcification. RT-qPCR and WB were utilized to detect the expression level of HDAC9. 30 male wild-type Wistar rats aged from 6 to 8 weeks 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, immunohistochemical staining, and immunofluorescent staining.
Results
In vitro, alizarin red staining showed the calcificated RASMCs had more calcium salt deposits. Both WB and RT-qPCR showed the expression of HDAC9 in calcificated cells was increased. In vivo, alizarin red staining of the aorta showedccalcium deposition in the calcification group was significantly higher compared to control group. In the third-generation full-length transcriptome sequencing of rat aorta, the RNA expression of HDAC9 in the calcificated group increased gradually from 4 weeks to 12 weeks, and was significantly higher than that in 4- and 16-week control groups. The immunohistochemical staining and immunofluorescent staining indicated the expression of HDAC9 in the aorta of the 12-week calcification group was significantly increased, compared to the 4- and 16-week control group.
Conclusion
Histone deacetylase 9 could contribute to the development of vascular calcification in chronic kidney disease.