Lanthanum Acetate Inhibits Vascular Calcification Induced by Vitamin D3 Plus Nicotine in Rats

Abstract

Lanthanum, a rare earth element, has been used to decrease serum phosphorus level in patients with chronic renal disease and hyperphosphatemia. We aimed to observe the effect and mechanism of two doses of lanthanum acetate (375 and 750 mg/kg/day) on vascular calcification induced by vitamin D3 plus nicotine treatment in rats for 4 weeks. As compared with control rats, rats with calcification showed widespread calcified nodules and irregular elastic fibers in calcified aorta on von Kossa calcium staining and increased aortic calcium and phosphorus contents, alkaline phosphatase (ALP) activity and bone-related protein expressions for osteopontin (OPN) and type III sodium dependent phosphate cotransporter Pit-1 (Pit-1). After treatment with either dose of lanthanum acetate, the calcified nodules and degree of irregular elastic fibers decreased in aortas. Lanthanum acetate at 750 mg/kg/day was more effective than 375 mg/kg/day in lessening vascular calcification by significantly reducing plasma phosphorus level, calcium x phosphorus product and ALP activity, by 30.3%, 28.6%, and 68.6%, respectively; reducing aortic phosphorus and calcium contents and ALP activity, by 48%, 53.1%, and 63.5% (all P < 0.01), respectively; reducing aortic mRNA level of OPN and Pit-1, by 55.8% (P < 0.01) and 38.8% (P < 0.05) and protein level of OPN and Pit-1, by 37.2% and 27.2% (both P < 0.01), respectively; and increasing carboxylated matrix Gla-protein (MGP) protein expression by 33.7% (P < 0.05), as compared with rats treated with vitamin D3 and nicotine alone. Lanthanum acetate could effectively inhibit the pathogenesis of vascular calcification.

Attenuation of aortic calcification with lanthanum carbonate versus calcium‐based phosphate binders in haemodialysis: A pilot randomized controlled trial

“…Experimental studies have reported beneficial effects of lanthanum on reduction of VC 18–20 . Whether this benefit is related to effective phosphate reduction with lanthanum or additional mechanisms is unclear.…”

“…Experimental studies have reported beneficial effects of lanthanum on reduction of VC. [18][19][20] Whether this benefit is related to effective phosphate reduction with lanthanum or additional mechanisms is unclear. One study involving lanthanum administered to rats demonstrated suppression of osteoblastic differentiation of vascular smooth muscle cells, an effect perhaps mediated by activation of several pathways.…”

“…15,16 LC has also been compared with sevelamer hydrochloride in a randomized study in a dialysis population showing similar achievement of serum phosphate levels. 17 Experimental studies assessing lanthanum suggest a benefit on reducing VC [18][19][20] but there is limited clinical data on the effect of this agent on VC in CKD. The main aim of this study was to evaluate the effects of LC compared with calcium-based phosphate binders on VC in HD patients in a pilot randomized controlled trial.…”

Adrenomedullin attenuates vascular calcification in fructose‐induced insulin resistance rats

“…Haematoxylin–eosin (HE) and Von Kossa staining were respectively carried out in these sections (Zhou et al . , ). Von Kossa staining was used to observe calcium deposits in aorta.…”

Vascular Calcification and ESRD

“…Early studies in animals suggest that the noncalcium-based phosphate binder lanthanum, as well as calcimimetic drugs, may decrease vascular calcification, but this has yet to be verified in humans or linked to reduced mortality (33,34). Human trials involving the use of a wide range of therapies including VDRAs (35), calcimimetics (36), bisphosphonates (37), and sodium thiosulfate (38) are planned or already underway.…”