Lanthanum acetate inhibits vascular calcification induced by vitamin D3 plus nicotine in rats.
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.
Zhou
Ye-Bo
YB
Department of Physiology and Pathophysiology, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, 100191, Beijing, China.
Jin
Shao-Ju
SJ
Cai
Yan
Y
Teng
Xu
X
Chen
Li
L
Tang
Chao-Shu
CS
Qi
Yong-Fen
YF
D000085:Acetates / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D002114:Calcinosis / Q000097:blood / Q000139:chemically induced* / Q000517:prevention & control*; D002118:Calcium / Q000097:blood; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002762:Cholecalciferol / Q000494:pharmacology*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007811:Lanthanum / Q000097:blood / Q000494:pharmacology*; D008297:Male; D009538:Nicotine / Q000009:adverse effects*; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D010758:Phosphorus / Q000097:blood; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050611:Sodium-Phosphate Cotransporter Proteins, Type III / Q000235:genetics / Q000378:metabolism; D000097568:Matrix Gla Protein
D000085:Acetates; D002118:Calcium; D002135:Calcium-Binding Proteins; D002762:Cholecalciferol; D016326:Extracellular Matrix Proteins; D007811:Lanthanum; D009538:Nicotine; D053495:Osteopontin; D010758:Phosphorus; D012333:RNA, Messenger; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D000097568:Matrix Gla Protein; C533640:lanthanum(III) acetate