Abstract Arterial medial calcification is an independent risk factor for mortality in chronic kidney disease. We previously reported that knock-down of PKCα expression increases high phosphate-induced mineral deposition by vascular smooth muscle cells in vitro . This new study tests the hypothesis that PKCα regulates uremia-induced medial calcification in vivo . Female wild-type and PKCα −/− mice underwent a two-stage subtotal nephrectomy and were fed a high phosphate diet for 8 weeks. X-ray micro computed tomography demonstrated that uremia-induced medial calcification was increased in the abdominal aorta and aortic arch of PKCα −/− mice compared to wild-types. Blood urea nitrogen was also increased in PKCα −/− mice compared to wild-types; there was no correlation between blood urea nitrogen and calcification in PKCα −/− mice. Phosphorylated SMAD2 immunostaining was detected in calcified aortic arches from uremic PKCα −/− mice; the osteogenic marker Runx2 was also detected in these areas. No phosphorylated SMAD2 staining were detected in calcified arches from uremic wild-types. PKCα knock-down increased TGF-β1-induced SMAD2 phosphorylation in vascular smooth muscle cells in vitro , whereas the PKCα activator prostratin decreased SMAD2 phosphorylation. In conclusion, loss of PKCα increases uremia-induced medial calcification. The PKCα/TGF-β signaling axis could therefore represent a new therapeutic target for arterial medial calcification in chronic kidney disease.

Loss of PKCα increases arterial medial calcification in a uremic mouse model of chronic kidney disease