Involvement of COMMD5 in Vascular Calcification in CKD

Background: Chronic kidney disease (CKD) is a prevalent and recurring health condition affecting a significant number of individuals. Among CKD patients, approximately 2-3% progress to end-stage renal disease (ESRD). Vascular calcification emerges as a prevalent complication in ESRD cases and has a strong correlation with the incidence of cardiovascular events. The disruption of calcium and phosphorus metabolism stands out as a primary factor contributing to vascular calcification. Recently, the hypertension-associated calcium regulatory gene (HCaRG) unveiled a connection with COMM domain-containing 5 (COMMD5). Identified as a gene influenced by extracellular calcium levels, COMMD5 encodes a compact intracellular protein composed of 225 amino acids. Past research suggests that parathyroidectomy (PTX) can reduce vascular calcification, and increased levels of COMMD5 are associated with decreased blood pressure. Nevertheless, the literature lacks substantial reports on the relationship between COMMD5 and vascular calcification. Our hypothesis ventures that COMMD5 could indeed be intricately linked to chronic vascular calcification. Methods: The blood vessels of the arteriovenous fistula are tested for calcification and COMMD5 expression. Human aortic smooth muscle cells (HASMC) and rat aortas were cultured in vitro and incubated with high phosphorus. Results: (1)COMMD5 expression is reduced in arteriovenous fistula vascular calcified tissues.(2)In comparison to the control group, the expression of COMMD5 in HASMC exhibited lower levels under high phosphorus stimulation.(3)HASMCs were subjected to stimulation using small interfering RNA (siRNA). This led to an upregulation of Runt-related transcription factor 2 (RUNX2) expression and downregulation of Anti-Smooth Muscle Antibody (α-SMA) expression in the cells.(4)Rat aortas were cultured in vitro and incubated with high phosphorus to stimulate isolated arteries. Upon conducting alizarin red staining, the group incubated with COMMD5 under high phosphorus stimulation displayed reduced levels of calcification in comparison to the high phosphorus group. Conclusion: COMMD5 plays a crucial role in inhibiting calcification in human aortic smooth muscle cells, consequently contributing to the reduction of vascular calcification. Funding: Government Support – Non-U.S.