INVESTIGADORES
PIROLA Carlos Jose
artículos
Título:
Losartan reduces liver expression of plasminogen activator inhibitor-1 (PAI-1) in
Autor/es:
ROSSELLI MS; BURGUEÑO A; CARABELLI J; SCHUMAN M; PIROLA CJ,; SOOKOIAN S
Revista:
ATHEROSCLEROSIS
Editorial:
ELSEVIER IRELAND LTD
Referencias:
Año: 2009 vol. 206 p. 119 - 126
ISSN:
0021-9150
Resumen:
a b s t r a c t
Objective: To evaluate the effect of losartan-an angiotensin II type 1 receptor (AT1R) antagonist- and
telmisartan-an AT1R blocker with insulin-sensitizing properties-, on the hepatic expression of plasminogen
activator inhibitor-1 (PAI-1) in a rat model of nonalcoholic fatty liver disease (NAFLD).
Methods: Rats were given a high-fat diet (HFD) for 8 weeks and after this period were randomly divided
into 3 groups. For 12 weeks along with the same access to HFD, one group (9 rats) received losartan and
another group received telmisartan (10 rats), both at 10 mg/kg intraperitoneally (ip) every 24 h. The third
group (8 rats) received saline ip along with the HFD. Finally, a control group (6 rats)was fed with standard
chow diet for 20 weeks.
Results: Fatty liver was reverted by both losartan and telmisartan. Both drugs had bene.cial effects on
insulin resistance, reaching statistical signi.cance in telmisartan group. Expression of hepatic mRNA of
PAI-1 showed a 42% decrease in losartan-treated rats incomparison with bothHFDgroup and telmisartantreated
rats. To further evaluate this differential effect on PAI-1 expression, we explored the effect of the
drugs on liver expression of TNF², PEPCK-C and PPAR², and no signi.cant differences were observed.
Conclusion: These results indicate that AT1R blockers could be eligible drugs for reducing hepatic lipid
accumulation in patients with NAFLD. However, only 12 weeks of losartan treatment strongly reduced
hepatic PAI-1 gene expression. These differences could provide even more effective options for preventing
fatty liver disease and its cardiovascular complications.
© 2009 Elsevier Ireland Ltd. All rights reserved.