Aldosterone inhibits endothelial morphogenesis and angiogenesis through the downregulation of vascular endothelial growth factor receptor-2 expression subsequent to peroxisome proliferator-activated receptor gamma

2012 ◽  
Vol 129 (3-5) ◽  
pp. 145-152 ◽  
Author(s):  
Miki Fujii ◽  
Isao Inoki ◽  
Makoto Saga ◽  
Norihiro Morikawa ◽  
Ken-ichiro Arakawa ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Peroxisome Proliferator ◽  
Vascular Endothelial ◽  
Peroxisome Proliferator Activated Receptor ◽  
Endothelial Growth Factor

scholarly journals Adverse Adipose Phenotype and Hyperinsulinemia in Gravid Mice Deficient in Placental Growth Factor

Endocrinology ◽  
2008 ◽  
Vol 149 (5) ◽  
pp. 2176-2183 ◽  
Author(s):  
Bianca Hemmeryckx ◽  
Rita van Bree ◽  
Berthe Van Hoef ◽  
Lisbeth Vercruysse ◽  
H. Roger Lijnen ◽  
...  
Keyword(s):  
Growth Factor ◽  
Adrenergic Receptors ◽  
Growth Factor Receptor ◽  
Placental Growth Factor ◽  
Peroxisome Proliferator ◽  
Vascular Endothelial ◽  
Wild Type ◽  
Peroxisome Proliferator Activated Receptor ◽  
Adipocyte Hypertrophy ◽  
Endothelial Growth Factor

Pregnancy-induced metabolic changes are regulated by signals from an expanded adipose organ. Placental growth factor (PlGF), acting through vascular endothelial growth factor receptor-1, may be among those signals. There is a steep rise in circulating PlGF during normal pregnancy, which is repressed in gravidas who develop preeclampsia. PlGF-deficiency in mice impairs adipose vascularization and development. Here we studied young-adult PlGF-deficient (PlGF−/−) and wild-type mice on a high-fat diet in the nongravid state and at embryonic day (E) 13.5 or E18.5 of gestation. Litter size and weight were normal, but E18.5 placentas were smaller in PlGF−/− pregnancies. PlGF−/− mice showed altered intraadipose dynamics, with the following: 1) less blood vessels and fewer brown, uncoupling protein (UCP)-1-positive, adipocytes in white sc and perigonadal fat compartments and 2) white adipocyte hypertrophy. The mRNA expression of β3-adrenergic receptors, peroxisome proliferator-activated receptor-γ coactivator-1α, and UCP-1 was decreased accordingly. Moreover, PlGF−/− mice showed hyperinsulinemia. Pregnancy-associated changes were largely comparable in PlGF−/− and wild-type dams. They included expanded sc fat compartments and adipocyte hypertrophy, whereas adipose expression of key angiogenesis/adipogenesis (vascular endothelial growth factor receptor-1, peroxisome proliferator-activated receptor-γ2) and thermogenesis (β3-adrenergic receptors, peroxisome proliferator-activated receptor-γ coactivator-1α, and UCP-1) genes was down-regulated; circulating insulin levels gradually increased during pregnancy. In conclusion, reduced adipose vascularization in PlGF−/− mice impairs adaptive thermogenesis in favor of energy storage, thereby promoting insulin resistance and hyperinsulinemia. Pregnancy adds to these changes by PlGF-independent mechanisms. Disturbed intraadipose dynamics is a novel mechanism to explain metabolic changes in late pregnancy in general and preeclamptic pregnancy in particular.

scholarly journals Role of Peroxisome Proliferator-Activated Receptor Alpha in the Control of Cyclooxygenase 2 and Vascular Endothelial Growth Factor: Involvement in Tumor Growth

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-10 ◽  
Author(s):  
Raquel Grau ◽  
Manuel D. Díaz-Muñoz ◽  
Cristina Cacheiro-Llaguno ◽  
Manuel Fresno ◽  
Miguel A. Iñiguez
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Cell Growth ◽  
Tumor Growth ◽  
Peroxisome Proliferator ◽  
Vascular Endothelial ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cox 2 ◽  
Endothelial Growth Factor

A growing body of evidence indicates that PPAR (peroxisome proliferator-activated receptor)αagonists might have therapeutic usefulness in antitumoral therapy by decreasing abnormal cell growth, and reducing tumoral angiogenesis. Most of the anti-inflammatory and antineoplastic properties of PPAR ligands are due to their inhibitory effects on transcription of a variety of genes involved in inflammation, cell growth and angiogenesis. Cyclooxygenase (COX)-2 and vascular endothelial growth factor (VEGF) are crucial agents in inflammatory and angiogenic processes. They also have been significantly associated to cell proliferation, tumor growth, and metastasis, promoting tumor-associated angiogenesis. Aberrant expression of VEGF and COX-2 has been observed in a variety of tumors, pointing to these proteins as important therapeutic targets in the treatment of pathological angiogenesis and tumor growth. This review summarizes the current understanding of the role of PPARαand its ligands in the regulation of COX-2 and VEGF gene expression in the context of tumor progression.

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