title: Guanidino compounds as cause of cardiovascular damage in chronic kidney disease: an in vitro evaluation.
abstract: Chronic kidney disease is considered a major cause of cardiovascular risk and non-traditional risk factors remain largely unknown. The in vitro toxicity of 10 guanidino compounds (GCs) was evaluated via a standardized approach on different cell systems of relevance in cardiovascular disease. The parameters evaluated were production of reactive oxygen species, expression of surface molecules, cell proliferation, cytotoxicity and calcification. Several GCs had a stimulatory effect on monocytes and granulocytes (SDMA, creatine and guanidinobutyric acid (GBA)). Some GCs (guandine (G), guanidinosuccinic acid (GSA) and SDMA) inhibited endothelial cell proliferation or reduced calcification in osteoblast-like human VSMC (ADMA, GSA and SDMA). Stimulation of osteoclastogenesis could be demonstrated for ADMA, G, guanidinoacetic acid and GBA in a RAW264.7 cell line. No compounds were cytotoxic to AoSMC or endothelial cells, nor influenced their viability. GCs, especially SDMA, likely contribute to cardiovascular complications in uremia, mainly those related to microinflammation and leukocyte activation.
authors.affiliation: Nephrology Division, Department of Internal Medicine, University Hospital Gent, De Pintelaan 185, Gent, Belgium.
authors.forename: Eva
authors.initials: E
authors.lastname: Schepers
authors.forename: Griet
authors.initials: G
authors.lastname: Glorieux
authors.forename: Laetitia
authors.initials: L
authors.lastname: Dou
authors.forename: Claire
authors.initials: C
authors.lastname: Cerini
authors.forename: Nathalie
authors.initials: N
authors.lastname: Gayrard
authors.forename: Loïc
authors.initials: L
authors.lastname: Louvet
authors.forename: Charlotte
authors.initials: C
authors.lastname: Maugard
authors.forename: Pierre
authors.initials: P
authors.lastname: Preus
authors.forename: Maria
authors.initials: M
authors.lastname: Rodriguez-Ortiz
authors.forename: Angel
authors.initials: A
authors.lastname: Argiles
authors.forename: Philippe
authors.initials: P
authors.lastname: Brunet
authors.forename: Gerald
authors.initials: G
authors.lastname: Cohen
authors.forename: Joachim
authors.initials: J
authors.lastname: Jankowski
authors.forename: Vera
authors.initials: V
authors.lastname: Jankowski
authors.forename: Ziad
authors.initials: Z
authors.lastname: Massy
authors.forename: Mariano
authors.initials: M
authors.lastname: Rodriguez
authors.forename: Raymond
authors.initials: R
authors.lastname: Vanholder
mesh_terms: D002114:Calcinosis / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000378:metabolism; D006146:Guanidines / Q000009:adverse effects / Q000633:toxicity; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism; D011946:Receptors, Antigen / Q000032:analysis / Q000187:drug effects; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000378:metabolism; D012306:Risk; D014511:Uremia / Q000150:complications / Q000378:metabolism
chemical_list: D006146:Guanidines; D017382:Reactive Oxygen Species; D011946:Receptors, Antigen