Pioglitazone suppresses macrophage proliferation in apolipoprotein-E deficient mice by activating PPARγ.
Atherosclerosis
; 286: 30-39, 2019 07.
Article
em En
| MEDLINE
| ID: mdl-31096071
ABSTRACT
BACKGROUND AND AIMS:
Local macrophage proliferation is linked to enhanced atherosclerosis progression. Our previous study found that troglitazone, a thiazolidinedione (TZD), suppressed oxidized low-density lipoprotein (Ox-LDL)-induced macrophage proliferation. However, its effects and mechanisms are unclear. Therefore, we investigated the effects of pioglitazone, another TZD, on macrophage proliferation.METHODS:
Normal chow (NC)- or high-fat diet (HFD)-fed apolipoprotein E-deficient (Apoe-/-) mice were treated orally with pioglitazone (10â¯mg/kg/day) or vehicle (water) as a control. Mouse peritoneal macrophages were used in in vitro assays.RESULTS:
Atherosclerosis progression was suppressed in aortic sinuses of pioglitazone-treated Apoe-/- mice, which showed fewer proliferating macrophages in plaques. Pioglitazone suppressed Ox-LDL-induced macrophage proliferation in a dose-dependent manner. However, treatment with peroxisome proliferator-activated receptor-γ (PPARγ) siRNA ameliorated pioglitazone-induced suppression of macrophage proliferation. Low concentrations (less than 100⯵mol/L) of pioglitazone, which can suppress macrophage proliferation, activated PPARγ in macrophages, but did not induce macrophage apoptosis. Pioglitazone treatment did not induce TUNEL-positive cells in atherosclerotic plaques of aortic sinuses in Apoe-/- mice.CONCLUSIONS:
Pioglitazone suppressed macrophage proliferation through PPARγ without inducing macrophage apoptosis. These findings imply that pioglitazone could prevent macrovascular complications in diabetic individuals.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
PPAR gama
/
Proliferação de Células
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Pioglitazona
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Macrófagos
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article