Extracellular calcium-sensing receptor is functionally expressed in human artery.

Area of Science:

• Cardiovascular Biology
• Nephrology
• Molecular Biology

Background:

• Accelerated medial calcification contributes to cardiovascular mortality in chronic kidney disease (CKD).
• Extracellular calcium (Ca2+) and vascular smooth muscle cells are implicated in vascular calcification.
• The calcium-sensing receptor (CaSR), a G protein-coupled receptor, has limited characterization in the cardiovascular system.

Purpose of the Study:

• To investigate the expression and function of the CaSR in human aortic smooth muscle cells (HAoSMC).
• To determine CaSR expression in arteries of normal subjects and end-stage renal disease (ESRD) patients.
• To explore the correlation between CaSR expression and CKD progression.

Main Methods:

• RT-PCR, Western blotting, and immunocytochemistry were used to detect CaSR mRNA and protein in HAoSMC and human arteries.
• HAoSMC were treated with Ca2+ or CaSR agonists (gentamicin, neomycin) to assess ERK1/2 phosphorylation.
• CaSR expression was inhibited using small-interference RNA to confirm CaSR-mediated signaling.

Main Results:

• CaSR mRNA and protein were expressed in HAoSMC.
• Ca2+, gentamicin, and neomycin induced dose- and time-dependent ERK1/2 phosphorylation in HAoSMC via CaSR.
• CaSR was detected in human arteries (smooth muscle and endothelial cells), with significantly lower expression in ESRD patients compared to controls.

Conclusions:

• A functional CaSR is present in human arteries.
• CaSR activation in HAoSMC leads to ERK1/2 pathway activation.
• Reduced CaSR expression in arteries correlates with CKD progression and may contribute to vascular calcification.