title: Dietary L-lysine prevents arterial calcification in adenine-induced uremic rats.
abstract: Vascular calcification (VC) is a life-threatening complication of CKD. Severe protein restriction causes a shortage of essential amino acids, and exacerbates VC in rats. Therefore, we investigated the effects of dietary l-lysine, the first-limiting amino acid of cereal grains, on VC. Male Sprague-Dawley rats at age 13 weeks were divided randomly into four groups: low-protein (LP) diet (group LP), LP diet+adenine (group Ade), LP diet+adenine+glycine (group Gly) as a control amino acid group, and LP diet+adenine+l-lysine·HCl (group Lys). At age 18 weeks, group LP had no VC, whereas groups Ade and Gly had comparable levels of severe VC. l-Lysine supplementation almost completely ameliorated VC. Physical parameters and serum creatinine, urea nitrogen, and phosphate did not differ among groups Ade, Gly, and Lys. Notably, serum calcium in group Lys was slightly but significantly higher than in groups Ade and Gly. Dietary l-lysine strongly suppressed plasma intact parathyroid hormone in adenine rats and supported a proper bone-vascular axis. The conserved orientation of the femoral apatite in group Lys also evidenced the bone-protective effects of l-lysine. Dietary l-lysine elevated plasma alanine, proline, arginine, and homoarginine but not lysine. Analyses in vitro demonstrated that alanine and proline inhibit apoptosis of cultured vascular smooth muscle cells, and that arginine and homoarginine attenuate mineral precipitations in a supersaturated calcium/phosphate solution. In conclusion, dietary supplementation of l-lysine ameliorated VC by modifying key pathways that exacerbate VC.
authors.affiliation: Departments of Geriatric Medicine and Nephrology and.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Shimomura
authors.affiliation: Departments of Geriatric Medicine and Nephrology and.
authors.forename: Isao
authors.initials: I
authors.lastname: Matsui
authors.affiliation: Comprehensive Kidney Disease Research, Osaka University Graduate School of Medicine, Suita, Osaka, Japan;
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hamano
authors.affiliation: Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University, Suita, Osaka, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Ishimoto
authors.affiliation: Applied Analytical Group, Fundamental Technology Laboratories, Institute for Innovation, Ajinomoto Co., Inc., Kawasaki-ku, Kawasaki, Kanagawa, Japan;
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Katou
authors.affiliation: Pharmacology Research Laboratory, Research Institute, Ajinomoto Pharmaceutical Co., Ltd., Kawasaki-ku, Kawasaki, Kanagawa, Japan; and.
authors.forename: Kenji
authors.initials: K
authors.lastname: Takehana
authors.affiliation: Departments of Geriatric Medicine and Nephrology and.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Departments of Geriatric Medicine and Nephrology and.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kusunoki
authors.affiliation: Departments of Geriatric Medicine and Nephrology and.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Mori
authors.affiliation: Departments of Geriatric Medicine and Nephrology and.
authors.forename: Chikako
authors.initials: C
authors.lastname: Nakano
authors.affiliation: Departments of Geriatric Medicine and Nephrology and.
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Obi
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Fujii
authors.affiliation: Departments of Geriatric Medicine and Nephrology and.
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Takabatake
authors.affiliation: Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University, Suita, Osaka, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Nakano
authors.affiliation: Comprehensive Kidney Disease Research, Osaka University Graduate School of Medicine, Suita, Osaka, Japan;
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Tsubakihara
authors.affiliation: Departments of Geriatric Medicine and Nephrology and isaka@kid.med.osaka-u.ac.jp.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Isaka
authors.affiliation: Departments of Geriatric Medicine and Nephrology and.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
mesh_terms: D000225:Adenine / Q000008:administration & dosage; D000409:Alanine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001120:Arginine / Q000494:pharmacology; D002118:Calcium / Q000097:blood / Q000652:urine; D002130:Calcium Phosphates / Q000378:metabolism; D002478:Cells, Cultured; D011232:Chemical Precipitation / Q000187:drug effects; D003404:Creatinine / Q000652:urine; D019587:Dietary Supplements; D006709:Homoarginine / Q000494:pharmacology; D006801:Humans; D008239:Lysine / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects; D010024:Osteoporosis / Q000517:prevention & control; D011392:Proline / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012996:Solutions; D014511:Uremia / Q000139:chemically induced / Q000150:complications / Q000178:diet therapy*; D061205:Vascular Calcification / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D002130:Calcium Phosphates; D012996:Solutions; D006709:Homoarginine; D001120:Arginine; C020243:calcium phosphate; D011392:Proline; D003404:Creatinine; D000225:Adenine; D008239:Lysine; D000409:Alanine; D002118:Calcium