PRMT3 methylates HIF-1α to enhance the vascular calcification induced by chronic kidney disease

Area of Science:

• Cardiovascular Biology
• Nephrology
• Molecular Medicine

Background:

• Medial vascular calcification is a prevalent complication in chronic kidney disease (CKD).
• This condition significantly impairs patient health and quality of life.
• The underlying mechanisms of vascular calcification in CKD require further elucidation.

Purpose of the Study:

• To investigate the role of protein arginine methyltransferase 3 (PRMT3) in CKD-induced vascular calcification.
• To explore the molecular pathways through which PRMT3 influences vascular calcification.

Main Methods:

• Established a CKD mouse model using a high calcium and phosphorus diet.
• Induced osteogenic differentiation in vascular smooth muscle cells (VSMCs) in vitro using β-glycerophosphate (β-GP).
• Utilized PRMT3 inhibitors and gene knockdown techniques, alongside analysis of hypoxia-induced factor 1α (HIF-1α) methylation.

Main Results:

• PRMT3 expression was elevated in VSMCs from CKD mice and in β-GP-treated VSMCs.
• PRMT3 inhibition or knockdown reduced vascular calcification and VSMC osteogenic differentiation by suppressing glycolysis.
• PRMT3 interacted with HIF-1α, and PRMT3 depletion decreased HIF-1α methylation and protein expression.

Conclusions:

• PRMT3 plays a significant role in promoting vascular calcification in CKD.
• PRMT3 regulates VSMC osteogenic differentiation and glycolysis through HIF-1α methylation.
• Targeting PRMT3 may offer a therapeutic strategy for managing vascular calcification in CKD.