Introduction:
Vascular calcification is an important risk factor for increased incidence and mortality from cardiovascular disease in patients with chronic kidney disease (CKD). Currently, there is no proven method for treating vascular calcification in CKD. Here we investigate new targets for controlling vascular calcification in CKD.
Methods:
In vivo, we constructed a model of vascular calcification in CKD rats by 5/6 nephrectomy and a high-phosphorus diet. Arteries were collected for nanopore full-length transcriptome sequencing and subsequent experiments. In vitro, osteogenic trans-differentiation of vascular smooth muscle cells (VSMCs) was induced by medium supplemented with calcium chloride and β-glycerophosphate. Nanopore full-length transcriptome sequencing of the arteries was used to identify candidate genes contributing to vascular calcification in CKD. The effect of the screened key gene on the osteogenic trans-differentiation of VSMCs was investigated both in vitro and in vivo.
Results:
One of the key genes related to vascular calcification in CKD is aryl hydrocarbon receptor nuclear translocator-like (Arntl). Multiple immunofluorescence staining demonstrated that calcified arteries had elevated Arntl expression, which colocalized with the osteogenic marker run-related transcription factor 2 (Runx2). In osteogenic trans-differentiated VSMCs, Arntl expression was upregulated in vitro. Arntl knockout mediated by CRISPR/Cas9 exacerbates osteogenic trans-differentiation in VSMCs, while Arntl overexpression by a plasmid reduced osteogenic trans-differentiation in VSMCs.
Conclusions:
Our study revealed that Arntl inhibits osteogenic trans-differentiation of VSMCs during vascular calcification in CKD, providing a new insight for further exploration of the mechanism underlying vascular calcification in CKD.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.