Vascular Calcification Induced by Chronic Kidney Disease Is Mediated by an Increase of 1α-Hydroxylase Expression in Vascular Smooth Muscle Cells.

Vascular calcification (VC) is a complication of chronic kidney disease that predicts morbidity and mortality. Uremic serum promotes VC, but the mechanism involved is unknown. A role for 1,25(OH)2 D3 in VC has been proposed, but the mechanism is unclear because both low and high levels have been shown to increase it. In this work we investigate the role of 1,25(OH)2 D3 produced in vascular smooth muscle cells (VSMCs) in VC. Rats with subtotal nephrectomy and kidney recipient patients showed increased arterial expression of 1α-hydroxylase in vivo. VSMCs exposed in vitro to serum obtained from uremic rats also showed increased 1α-hydroxylase expression. Those increases were parallel to an increase in VC. After 6 days with high phosphate media, VSMCs overexpressing 1α-hydroxylase show significantly higher calcium content and RUNX2 expression than control cells. 1α-hydroxylase null mice (KO) with subtotal nephrectomy and treated with calcitriol (400 ng/kg) for 2 weeks showed significantly lower levels of vascular calcium content, Alizarin red staining, and RUNX2 expression than wild-type (WT) littermates. Serum calcium, phosphorus, blood urea nitrogen (BUN), PTH, and 1,25(OH)2 D3 levels were similar in both calcitriol-treated groups. In vitro, WT VSMCs treated with uremic serum also showed a significant increase in 1α-hydroxylase expression and higher calcification that was not observed in KO cells. We conclude that local activation of 1α-hydroxylase in the artery mediates VC observed in uremia. © 2016 American Society for Bone and Mineral Research.

Microangiopathy of common carotid vasa vasorum in type 1 diabetes mellitus.

OBJECTIVE: We hypothesize that in type 1 diabetes vasa vasorum (VV) are affected by microangiopathic changes. For this purpose, we assessed the status of the VV signal in patients with type 1 diabetes. METHODS: The VV signal at the arterial adventitia of the common carotid artery was evaluated by contrast-enhanced ultrasound imaging. The VV contrast agent signal was quantified in an plaque-free arterial segment as the ratio of the adventitial signal and that of the lumen of the artery. We studied 113 type 1 diabetic patients, 60 with and 53 without retinopathy and without known cardiovascular disease, and a group of 78 non-diabetic subjects free of cardiovascular risk factors. All study subjects underwent a clinical evaluation. RESULTS: The mean ± standard deviation VV signal of healthy subjects was 0.562 ± 0.135. Type 1 diabetic patients showed a higher adventitial VV signal (0.723 ± 0.128) than non-diabetic subjects (P < 0.0001). After adjustment for cardiovascular risk confounders, this difference remained significant. No differences in VV signal, or common carotid intima-media thickness, between subjects with and without retinopathy were found. CONCLUSIONS: Type 1 diabetic patients, independently of their retinopathy status, show an increased angiogenesis of the VV of the common carotid artery compared with non-diabetic subjects. Diabetic microangiopathy, that according to our results would also affect the wall of the large arteries, could be a factor contributing to atherosclerosis in type 1 diabetes mellitus.