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Titolo:
Troglitazone, but not rosiglitazone, inhibits Na/H exchange activity and proliferation of macrovascular endothelial cells
Autore:
de Dios, ST; Hannan, KM; Dilley, RJ; Hill, MA; Little, PJ;
Indirizzi:
Baker Med Res Inst, Cell Biol Diabet Lab, Melbourne, Vic 8008, Australia Baker Med Res Inst Melbourne Vic Australia 8008 urne, Vic 8008, Australia
Titolo Testata:
JOURNAL OF DIABETES AND ITS COMPLICATIONS
fascicolo: 3, volume: 15, anno: 2001,
pagine: 120 - 127
SICI:
1056-8727(200105/06)15:3<120:TBNRIN>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACTIVATED RECEPTOR-GAMMA; AORTIC SMOOTH-MUSCLE; PROTEIN-KINASE; GENE-EXPRESSION; NA+/H+ EXCHANGE; HIGH-GLUCOSE; GROWTH; MECHANISMS; ANTIPORT; PH;
Keywords:
macrovascular disease; sodium hydrogen exchange; endothelial cells; rosiglitazone; troglitazone;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
29
Recensione:
Indirizzi per estratti:
Indirizzo: Little, PJ Baker Med Res Inst, Cell Biol Diabet Lab, POB 6492, Melbourne, Vic 8008, Australia Baker Med Res Inst POB 6492 Melbourne Vic Australia 8008 tralia
Citazione:
S.T. de Dios et al., "Troglitazone, but not rosiglitazone, inhibits Na/H exchange activity and proliferation of macrovascular endothelial cells", J DIABET C, 15(3), 2001, pp. 120-127

Abstract

Diabetes is associated with a high level of mortality due to cardiovascular disease resulting from accelerated coronary artery atherosclerosis. A current focus for investigation of atherosclerotic mechanisms is the vascular endothelium since physical or functional injury may represent an initiatingstep for atherogenesis. Thiazolidinediones (TZDs) are the newest class of drugs for the treatment of insulin resistance and its metabolic consequences; they are peroxisome proliferator-activating receptor (PPAR)-gamma ligands that act as insulin-sensitizing agents. We are interested in the contribution of direct vascular actions to the clinical utility of these agents. Weinvestigated the effect troglitazone and rosiglitazone on endothelial cellproliferation in low- and high-glucose media and further explored their action on the ubiquitous membrane transport system, the Na/H exchanger (NHE),which has been implicated in regulating the growth of vascular cells. Experiments were conducted in cultured bovine aortic endothelial cells (BAECs). Cell proliferation was assessed by cell counting, and NHE activity was determined in cells loaded with the pH-sensitive fluorescent dye, 2 ', 7 ' -bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein acetoxymethyl ester (BCECF-PLM). Troglitazone caused a dose-dependent inhibition of endothelial cell proliferation with approximately 50% inhibition at 10 muM. Troglitazone inhibited endothelial cell proliferation with similar, potency under low- (5 mM) and high-glucose (25 mM) concentrations. Rosiglitazone had no significanteffect on endothelial cell proliferation at concentrations of up to 100 muM under low- or high-glucose concentrations. The NHE inhibitor, 3-metlylsulfonyl-4-piperidinobenzoyl guanidine (HOE 694), caused dose dependent inhibition of BAEC proliferation, which was independent of the media glucose concentration. Acute exposure of cells to troglitazone(10 muM) and rosiglitazone (30 muM) during recovery from acidosis showed slight but significant (P <.05) inhibition of NHE activity by troglitazone, but no significant(P > .05) effect by rosiglitazone. Exposure of cells to either drug for 24 h revealed no chronic regulation of NHE activity Our data demonstrate that troglitazone has similar actions in endothelial cells as in vascular smooth muscle. The absence of rosiglitazone effects, a more potent PPAR-gamma activator,suggests that the observed actions of troglitazone may be at least partially independent of PPAR-gamma. The effects of troglitazone and rosiglitazoneon endothelial cell proliferation and NHE activity, although contrasting, are consistent with a central signalling role of this transporter in cell proliferation. (C) 2001 Elsevier Science Inc. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/01/20 alle ore 01:59:02