Login




Metabolismo calcio-fosforo / nefrolitiasi

LANTHANUM CHLORIDE AND THE CALCIMIIMETIC CALINDOL PREVENT VASCULAR SMOOTH MUSCLE CELLS CALCIFICATION

Questo Abstract è stato accettato come Poster. Clicca qui per visualizzare

Abstract

Phosphate (Pi)-binders are commonly used in dialysis patients to control high Pi levels, that associated with vascular calcification (VC). The aim of this study was to investigate the effects of lanthanum (La3+) on the progression of Pi-induced VC in vitro.

Rat vascular smooth muscle cells (VSMCs) were cultured in the presence of high Pi (5 mM) and calcium (Ca) deposition analysis was performed to quantify VC. To investigate VSMCs osteoblastic differentiation, we analyzed alpha-actin and SM22alpha protein content and core-binding factor alpha-1 (Cbfalpha1/RUNX2) mRNA expression.

Pi-induced Ca deposition was inhibited by La3+ chloride (LaCl3), with a maximal effect at 100 microM (59.0 ± 2.5%). Furthermore, we studied the effects on VC of Ca Sensing Receptor (CaSR) agonists. Gadolinium (Gd3+) chloride, neomycin, spermine, and the calcimimetic calindol significantly inhibited Pi-induced VC (55.9 ± 2.2%, 37.3 ± 4.7%, 30.2 ± 5.7% and 63.8 ± 5.7%, respectively). To investigate the hypothesis that La3+ reduces the progression of VC by interacting with the CaSR, we performed a concentration-response curve of La3+ in presence of a sub-effective concentration of calindol (10 nM). Interestingly, this curve was shifted to the left (IC50 24.2 microM), compared to the curve in the presence of La3+ alone (IC50 45.5 microM). Interestingly, La3+ was able to prevent the high Pi-induced reduction of both alpha-actin and SM22alpha protein content, delaying VSMCs osteoblastic differentiation, with no effects on Cbfalpha-1/RUNX2 mRNA expression.

We demonstrated that La3+ per se and in combination with calindol reduced significantly the progression of VC. In addition, La3+ preserved VSMCs phenotype by high Pi-induced alterations. These in vitro preliminary data suggest the design for clinical trials to investigate the effects of different treatments for dialysis patients affected by hyperphosphatemia and VC.

M. Cozzolino(1), P. Ciceri(1), F. Elli(1), I. Brenna(1), D. Brancaccio(1)
((1)Laboratorio Di Nefrologia Sperimentale, University Of Milan )
Non sono presenti commenti
Figure
Realizzazione: Tesi S.p.A.

Per assistenza contattare: Claudia Ingrassia, Tesi S.p.A.
0172 476301 — claudia.ingrassia@gruppotesi.com