The combination of lanthanum chloride and the calcimimetic calindol delays the progression of vascular smooth muscle cells calcification.
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 chloride (LaCl(3)) on the progression of high Pi-induced VC, in rat vascular smooth muscle cells (VSMCs). Pi-induced Ca deposition was inhibited by LaCl(3), with a maximal effect at 100μM (59.0±2.5% inhibition). Furthermore, we studied the effects on VC of calcium sensing receptor (CaSR) agonists. Gadolinium 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 LaCl(3) reduces the progression of VC by interacting with the CaSR, we performed a concentration-response curve of LaCl(3) in presence of a sub-effective concentration of calindol (10nM). Interestingly, this curve was shifted to the left (IC(50) 9.6±2.6μM), compared to the curve in the presence of LaCl(3) alone (IC(50) 19.0±4.8μM). In conclusion, we demonstrated that lanthanum chloride effectively reduces the progression of high phosphate-induced vascular calcification. In addition, LaCl(3) cooperates with the calcimimetic calindol in decreasing Ca deposition in this in vitro model. These results suggest the potential role of lanthanum in the treatment of VC induced by high Pi.
Renal Division and Laboratory of Experimental Nephrology, Dipartimento di Medicina e Chirurgia, Università di Milano, Milan, Italy.
Paola
P
Ciceri
Elisa
E
Volpi
Irene
I
Brenna
Francesca
F
Elli
Elisa
E
Borghi
Diego
D
Brancaccio
Mario
M
Cozzolino
D000818:Animals; D057966:Calcimimetic Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D007211:Indoles / Q000494:pharmacology*; D007811:Lanthanum / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009281:Naphthalenes / Q000494:pharmacology*; D010710:Phosphates / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D044169:Receptors, Calcium-Sensing / Q000819:agonists / Q000378:metabolism; D061205:Vascular Calcification / Q000139:chemically induced / Q000503:physiopathology*
C506457:(R)-2-(1-(1-naphthyl)ethyl-aminom-ethyl)indole; D057966:Calcimimetic Agents; D007211:Indoles; D009281:Naphthalenes; D010710:Phosphates; D044169:Receptors, Calcium-Sensing; C028521:lanthanum chloride; D007811:Lanthanum; D002118:Calcium