Oxidized LDL Regulates Vascular Endothelial Growth Factor Expression in Human Macrophages and Endothelial Cells Through Activation of Peroxisome Proliferator–Activated Receptor-γ

Inoue, Mayumi; Itoh, Hiroshi; Tanaka, Takuma; Chun, Tae Hwa; Doi, Kentaro; Fukunaga, Yasutomo; Sawada, Naoki; Yamshita, Jun; Masatsugu, Ken; Saito, Takatoshi; Sakaguchi, Shota; Sone, Masakatsu; Yamahara, Ken Ichi; Yurugi, Takami; Nakao, Kazuwa

doi:10.1161/01.atv.21.4.560

Cited by 144 publications

(100 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…34 However, although PPAR-␥ agonists have been shown previously to restore proangiogenic factors, upregulate HO-1, 10 and increase the production of VEGF in vitro [35][36][37] and in vivo, 18 rosiglitazone failed to alter angiogenic factors in the RUPP rat in the present study. A recent study, involving the induction of HO-1 in RUPP rats via the administration of cobalt (III) protoporphyrin IX chloride, demonstrated that, as a result of cobalt (III) protoporphyrin IX chloride treatment, placental expression of HO-1 was increased, and there was a significant shift in the angiostatic balance ratio (sFlt-1:VEGF).…”

Section: Discussioncontrasting

confidence: 71%

Peroxisome Proliferator-Activated Receptor-γ as a Potential Therapeutic Target in the Treatment of Preeclampsia

et al. 2011

View full text Add to dashboard Cite

Abstract-Preeclampsia is a multisystemic disorder of pregnancy characterized by hypertension, proteinuria, and maternal endothelial dysfunction. It is a major cause of maternal and perinatal morbidity and mortality and is thought to be attributable, in part, to inadequate trophoblast invasion. Peroxisome proliferator-activated receptor-␥ (PPAR-␥) is a ligand-activated transcription factor expressed in trophoblasts, and the vasculature of which activation has been shown to improve endothelium-dependent vasodilatation in hypertensive conditions. We investigated the effects of the administration of a PPAR-␥ agonist using the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia. The selective PPAR-␥ agonist, rosiglitazone, was administered to pregnant rats that had undergone RUPP surgery. To investigate whether any observed beneficial effects of PPAR-␥ activation were mediated by the antioxidant enzyme, heme oxygenase 1, rosiglitazone was administered in combination with the heme oxygenase 1 inhibitor tinprotoporphyrin IX. RUPP rats were characterized by hypertension, endothelial dysfunction, and elevated microalbumin:creatinine ratios. Rosiglitazone administration ameliorated hypertension, improved vascular function, and reduced the elevated microalbumin:creatinine ratio in RUPP rats. With the exception of microalbumin:creatinine ratio, these beneficial effects were abrogated in the presence of the heme oxygenase 1 inhibitor. Administration of a PPAR-␥ agonist prevented the development of several of the pathophysiological characteristics associated with the RUPP model of preeclampsia, via a heme oxygenase 1-dependent pathway. The findings from this study provide further insight into the underlying etiology of preeclampsia and a potential therapeutic target for the treatment of preeclampsia. (Hypertension. 2011;58:280-286.) • Online Data SupplementKey Words: peroxisome proliferator-activated receptor-␥ Ⅲ preeclampsia Ⅲ reduced uterine perfusion pressure Ⅲ hypertension Ⅲ heme oxygenase 1 Ⅲ vascular dysfunction P reeclampsia is a major cause of maternal and perinatal morbidity and mortality worldwide, causing Ϸ15% of all direct maternal deaths and mediating a 5-fold increase in perinatal mortality. 1 Although the underlying etiology of preeclampsia is poorly understood, it is characterized by a relatively hypoperfused placenta, which stimulates the maternal response manifesting as hypertension, vascular dysfunction, alterations in platelet aggregation, and a pro-oxidant state. 2 There is currently no effective pharmacological intervention available for the treatment of preeclampsia, and, consequently, pregnancies are often delivered preterm for maternal benefit, imposing the challenges of iatrogenic prematurity on the fetus. 3 Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that regulate the expression of a number of genes involved in cell differentiation and proliferation. 4 PPAR-␥ plays a predominant role in normal vascular function 5 and in the differ...

show abstract

Section: Discussioncontrasting

confidence: 71%

Peroxisome Proliferator-Activated Receptor-γ as a Potential Therapeutic Target in the Treatment of Preeclampsia

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Contradictory effects of 15d-PGJ 2 and other PPAR␥ agonists on COX-2 and VEGF expression have been described in the literature. Whereas some authors report that these agents suppress COX-2 or VEGF expression in a variety of cell lines after cell stimulation (16,17,41,42), other results indicate that 15d-PGJ 2 and other PPAR␥ agonists are inductors of COX-2 or VEGF expression (41,(43)(44)(45). Although these apparent discrepancies may have multiple causes, it is likely that 15d-PGJ 2 displays a dual effect; whereas this cyclopentenone induces basal COX-2 or VEGF expression, in most cases, presumably by PPAR␥ activation, it also is able to reduce the up-regulation of these genes by PPAR␥-dependent or -independent mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Activator Protein 1 Activation, Vascular Endothelial Growth Factor, and Cyclooxygenase-2 Expression by 15-Deoxy-Δ12,14-Prostaglandin J2 in Colon Carcinoma Cells: Evidence for a Redox-Sensitive Peroxisome Proliferator-Activated Receptor-γ-Independent Mechanism

2004

View full text Add to dashboard Cite

“…Increased VEGF levels have been reported in plasma from hypercholesterolemic individuals [13] and in coronary arteries from hypercholesterolemic pigs [14]. Moreover, it has been shown that oxidized LDL, a key molecule in the atherosclerotic process, can upregulate VEGF expression in macrophages and endothelial cells, at least partially through the activation of PPAR␥ [15]. In this context, assuming that VEGF acting through VEGFR-2 can be at least one of the factors responsible for the angiogenic processes required for atherosclerosis plaque development, we hypothesized that either of them could be upregulated in the vascular wall of apoE−/− mice.…”

Section: Introductionmentioning

confidence: 99%

Vitamins C and E downregulate vascular VEGF and VEGFR-2 expression in apolipoprotein-E-deficient mice

et al. 2003

View full text Add to dashboard Cite

Anti-angiogenic therapy reduces both plaque growth and intimal neovascularization in apolipoprotein-E-deficient mice (apoE−/−). Vascular endothelial growth factor (VEGF) has been suggested as playing a role in the development of atherosclerosis. We examined the hypothesis that VEGF and VEGF receptor-2 (VEGFR-2) expression is upregulated in apoE−/− and, since it could be driven by oxidative stress, tested whether dietary supplementation with vitamins C and E could downregulate it. Two-month-old apoE−/− received vitamin C combined with ␣-or ␤-tocopherol for 4 weeks. Aortic VEGF and VEGFR-2 expression were measured by RT-qPCR and western blot.ApoE−/− showed significantly higher expression of aortic VEGF and VEGFR-2 mRNA (P < 0.001) and protein (P < 0.001) than wild-type mice, as well as increased plasma VEGF (P < 0.001). Vitamin C and ␣-tocopherol significantly reduced aortic VEGF and VEGFR-2 expression in apoE−/− (P < 0.001), circulating VEGF (P < 0.01) and plasma lipid peroxidation (P < 0.01). apoE−/− receiving vitamin C and ␤-tocopherol showed diminished lipid peroxidation and VEGFR-2, but only partial reduction of VEGF expression.These data demonstrate that augmented VEGF and VEGFR-2 expression in apoE−/− vasculature can be downregulated by vitamins C and E, at least partially through oxidative stress reduction. This novel mechanism could contribute to explaining the beneficial effects of antioxidant vitamins in experimental atherosclerosis.

show abstract

Oxidized LDL Regulates Vascular Endothelial Growth Factor Expression in Human Macrophages and Endothelial Cells Through Activation of Peroxisome Proliferator–Activated Receptor-γ

Abstract: Abstract-Vascular endothelial growth factor

Cited by 144 publications

References 46 publications

Peroxisome Proliferator-Activated Receptor-γ as a Potential Therapeutic Target in the Treatment of Preeclampsia

Peroxisome Proliferator-Activated Receptor-γ as a Potential Therapeutic Target in the Treatment of Preeclampsia

Inhibition of Activator Protein 1 Activation, Vascular Endothelial Growth Factor, and Cyclooxygenase-2 Expression by 15-Deoxy-Δ12,14-Prostaglandin J2 in Colon Carcinoma Cells: Evidence for a Redox-Sensitive Peroxisome Proliferator-Activated Receptor-γ-Independent Mechanism

Vitamins C and E downregulate vascular VEGF and VEGFR-2 expression in apolipoprotein-E-deficient mice

Contact Info

Product

Resources

About