PPAR-γ agonists induce the expression of VEGF and its receptors in cultured cardiac myofibroblasts

Chintalgattu, Vishnu; Harris, Geoffrey; Akula, Shaw M.; Katwa, Laxmansa C.

doi:10.1016/j.cardiores.2007.01.010

Cited by 76 publications

(60 citation statements)

References 40 publications

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“…In our previous in vitro studies we demonstrated that treatment with PPAR-γ agonists resulted in the reduction of NF-κB activity in cardiac myofibroblasts isolated from the site of myocardial infarction [4]. The current study demonstrates increases in the PPAR-γ expression in these models.…”

Section: Introductionsupporting

confidence: 68%

PPAR-γ expression in animals subjected to volume overload and chronic Urotensin II administration

et al. 2008

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Activation of PPAR-γ through the administration of glitazones has shown promise in preserving function following cardiac injury, although recent evidence has suggested their use may be contraindicated in the case of severe heart failure. This study tested the hypothesis that PPAR-γ expression increases in a time dependent manner in response to chronic volume overload (VO) induced heart failure. Additionally, we attempted to determine what effect 4 week administration of Urotensin II (UTII) may have on PPAR-γ expression. VO induced heart failure was produced in Sprague-Dawley rats (n = 32) by aorta-caval fistula. Animals were sacrificed at 1, 4, and 14 weeks following shunt creation. In a separate set of experiments, animals were administered 300 pmol/kg/h of UTII for 4 weeks, subjected to 4 weeks of volume overload, or given UTII + VO. Densitometric analysis of left ventricular (LV) protein demonstrated PPAR-γ expression was significantly (*p < 0.05) upregulated at 4 and 14 weeks (31.5% and 37%, respectively) post-fistula formation compared to control values. PPAR-γ activation was decreased in the 4 and 14 week (39.16% and 42.4%, respectively), but not in the 1-week animals, and these changes did not correlate with NF-κB activity. Animals given UTII either with or without VO demonstrated increased expression of PPAR-γ as did animals subjected to 4 week VO alone. Animals given UTII either with or without VO had decreased activity vs. control. These data suggest PPAR-γ may play a role in the progression of heart failure, however, the exact nature has yet to be determined.

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Section: Introductionsupporting

confidence: 68%

PPAR-γ expression in animals subjected to volume overload and chronic Urotensin II administration

et al. 2008

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“…[25][26][27] However the relationship between PPARg and tight junctions awaits clarification. Recent studies have revealed that PPARg activation can upregulate the expression of vascular endothelial growth factor (VEGF), 4,28) which plays an important role in the regulation of tight junctions. In the present study, we believed that it may be PPARg-dependent pathway, rather than angiotensin II-related pathway, which led to the alteration of ZO-1 expression and localization induced by telmisartan.…”

Section: Discussionmentioning

confidence: 99%

“…1,2) Recently, it has been found that the ARB telmisartan has an interesting structural resemblance to the insulin sensitizer pioglitazone, a thiazolidinedione ligand of the peroxisome proliferator-activated receptor gamma (PPARg) which has significant roles in atherosclerosis. 3,4) Whether telmisartan could be used to treat atherosclerosis with these two roles is unknown.…”

mentioning

confidence: 99%

Telmisartan Increases the Permeability of Endothelial Cells through Zonula Occludens-1

Bian

Chen

2009

Biological & Pharmaceutical Bulletin

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Angiotensin receptor-1 blockers (ARBs) have been used for the treatment of atherosclerosis. Tight junctions are very important in the regulation of cellular permeability which may have a profound role in atherosclerosis. The relationship between them is unresolved. The expression and distribution of zonula occludens-1 (ZO-1), the permeability of cultured endothelial cells, and the activity of phosphatidylinositol 3-kinase (PI3K) were all detected with various methods after cultured endothelial cells were exposed to valsartan and the special ARB telmisartan or combined with PI3K inhibitor wortmannin or the peroxisome proliferator-activated receptor gamma antagonist GW9662. We found that telmisartan but not valsartan downregulated ZO-1 mRNA and protein levels, disrupted the distribution of ZO-1 in cultured endothelial cells, and increased the permeability of endothelial cells in a dose-dependent manner. When the PI3K inhibitor wortmannin was used, the effect induced by telmisartan was at least partly reversed. The role of the PI3K signaling pathway was further confirmed in the PI3K activity assay. GW9662 significantly blocked telmisartan-induced ZO-1 changes. Our results suggest that telmisartan disrupts the continuous pericellular distribution of ZO-1, downregulates the expression of ZO-1 in endothelial cells, and increases the permeability of endothelial cells at least partly through PI3K and the peroxisome proliferator-activated receptor gamma-dependent pathway.

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“…Both pathways are known to be relevant for the control of vascular growth and differentiation in vivo, as the transcription signals promote VEGF and other growth factors expression. In miofibroblasts, the activation of the peroxisome proliferator-activated receptor (PPAR)-γ by its agonists induces VEGF expression while simultaneously decreasing inflammation (NF-KB) (Chintalgattu et al, 2007). VEGFR2 expression is an additional target of PPAR activation in endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

In vivo anti-angiogenic effects further support the promise of the antineoplasic activity of methyl jasmonate

et al. 2010

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Molecular plant components have long been aimed at the angiogenesis and anti-angiogenesis pathways, and have been tested as sources for antineoplasic drugs with promising success. The present work deals with the anti-angiogenic effects of Methyl Jasmonate. Jasmonate derivatives were demonstrated to selectively damage the mitochondria of cancer cells. In vitro, 1-10 mM Methyl Jasmonate induced the cell death of the human umbilical vein endothelial cells (HUVEC) and the Murine melanoma cells (B16F10), while micromolar concentrations were ineffective. In vivo, comparable concentrations were toxic and reduced the vessel density of the Chorioallantoic Membrane of the Chicken Embryo (CAM). However, 1-10 µM concentrations produced a complex effect. There was increased capillary budding, but the new vessels were leakier and less organised than corresponding controls. It is suggested that not only direct toxicity, but also the drug effects upon angiogenesis are relevant to the antineoplasic effects of Methyl Jasmonate.Keywords: methyl jasmonate, antiangiogenesis, CAM model, endothelial cell culture, HUVEC. Efeitos antiangiogênicos in vivo convalidam a atividade antineoplásica potencial do metiljasmonato ResumoMoléculas de origem vegetal são, há muito, conhecidas como substâncias ativas sobre as vias de angiogênese e antiangiogênese e foram testadas como fonte de drogas antineoplásicas com sucesso promissor. Este trabalho trata dos efeitos antiangiogênicos do Metiljasmonato, um protótipo da família dos derivados do ácido jasmônico, que danificam seletivamente a mitocôndria de células neoplásicas. In vitro, metiljasmonato 1-10 mM promoveu a morte celular de células endoteliais humanas de cordão umbilical (HUVEC) e de melanoma murino (B16F10); concentrações micromolares foram inócuas. In vivo, concentrações equivalentes foram tóxicas e reduziram a densidade de vasos em membranas corioalantoicas de embrião de galinha (CAM). Entretanto, concentrações entre 1-10 µM produziram um efeito complexo. Ocorreu aumento no brotamento capilar, mas os novos vasos apresentaram-se frágeis e menos organizados que os controles correspondentes. Sugere-se que, além da toxicidade direta contra as células tumorais, a ação do metiljasmonato sobre a angiogênese seja relevante para seu efeito antineoplásico.Palavras-chave: metiljasmonato, antiangiogênese, modelo da CAM, cultura de células endoteliais, HUVEC.

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PPAR-γ agonists induce the expression of VEGF and its receptors in cultured cardiac myofibroblasts

Cited by 76 publications

References 40 publications

PPAR-γ expression in animals subjected to volume overload and chronic Urotensin II administration

PPAR-γ expression in animals subjected to volume overload and chronic Urotensin II administration

Telmisartan Increases the Permeability of Endothelial Cells through Zonula Occludens-1

In vivo anti-angiogenic effects further support the promise of the antineoplasic activity of methyl jasmonate

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