Oxidized LDL binding to LOX-1 upregulates VEGF expression in cultured bovine chondrocytes through activation of PPAR-γ

Kanata, S.; Akagi, Masao; Nishimura, Shunji; Hayakawa, Sumio; Yoshida, Kohji; Sawamura, Tatsuya; Munakata, Hiroshi; Hamanishi, Chiaki

doi:10.1016/j.bbrc.2006.07.133

Cited by 48 publications

(28 citation statements)

References 32 publications

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“…In these cells, PPAR␥-induced VEGF increase was functionally coupled to a decrease of nuclear factor-B activity (Chintalgattu et al, 2007). In addition, bovine articular chondrocytes have been shown to up-regulate VEGF via oxidized low-density lipoprotein-mediated PPAR␥ activation (Kanata et al, 2006). However, the specific PPAR␥ inhibitor GW9662 suppressed oxidized low-density lipoprotein-induced VEGF expression in chondrocytes, providing evidence that PPAR␥ activation was, in contrast to keratinocytes, pivotal to VEGF expression.…”

Section: Discussionmentioning

confidence: 99%

Keratinocyte-Derived Vascular Endothelial Growth Factor Biosynthesis Represents a Pleiotropic Side Effect of Peroxisome Proliferator-Activated Receptor-γ Agonist Troglitazone but Not Rosiglitazone and Involves Activation of p38 Mitogen-Activated Protein Kinase: Implications for Diabetes-Impaired Skin Repair

Schiefelbein

Seitz²,

Goren³

et al. 2008

Mol Pharmacol

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The peroxisome proliferator-activated receptors (PPARs) represent pharmacological target molecules to improve insulin resistance in type 2 diabetes mellitus. Here we assessed a functional connection between pharmacological activation of PPAR and vascular endothelial growth factor (VEGF) expression in keratinocytes and during diabetes-impaired acute skin repair in obese/obese (ob/ob) mice. PPAR␤/␦ agonist 4-[3-[4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]phenoxy]acetic acid (L165,041) and PPAR␥ agonists ciglitazone and troglitazone, but not rosiglitazone, potently induced VEGF mRNA and protein expression from cultured keratinocytes. Inhibitor studies revealed a strong functional dependence of troglitazoneand L165,041-induced VEGF expression on p38 and p42/44 mitogen-activated protein kinase (MAPK) activation in keratinocytes. Rosiglitazone also induced activation of p38 MAPK but failed to mediate the activation of p42/44 MAPK in the cells.

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Section: Discussionmentioning

confidence: 99%

Keratinocyte-Derived Vascular Endothelial Growth Factor Biosynthesis Represents a Pleiotropic Side Effect of Peroxisome Proliferator-Activated Receptor-γ Agonist Troglitazone but Not Rosiglitazone and Involves Activation of p38 Mitogen-Activated Protein Kinase: Implications for Diabetes-Impaired Skin Repair

Schiefelbein

Seitz²,

Goren³

et al. 2008

Mol Pharmacol

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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%

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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“…Kanata and his colleagues reported that ox-LDL markedly increases the expression of VEGF and activates a peroxisome proliferatoractivated receptor (PPAR)-gamma, which is attenuated by anti-LOX-1 antibody [84]. Hu et al further demonstrated that capillary sprouting induced by Ang II is related to elevated expression of VEGF, and anti-LOX-1 antibody markedly inhibits Ang II-induced VEGF expression [15].…”

Section: Lox-1 and Angiogenesismentioning

confidence: 95%

Angiogenesis is a Link Between Atherosclerosis and Tumorigenesis: Role of LOX-1

Jiang

Yan

Mehta

et al. 2011

Cardiovasc Drugs Ther

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Angiogenesis is defined as the formation of new blood vessels sprouting from pre-existing vessels. It plays an important role not only in physiological situations such as embryonic vascular development and wound healing, but also in pathological conditions including atherogenesis and evolution and spread of certain tumors. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), a receptor for oxidized low density lipoprotein (ox-LDL), is mainly expressed in endothelial cells. It has diverse physiological functions and it could be a link between atherogenesis and tumorigenesis. The risk factors for atherosclerosis like hypertension, diabetes mellitus and hyperlipidemia are associated with LOX-1. Dyslipidemia and obesity are also being recognized as risk factor for certain tumors. LOX-1 is also found to be important for maintaining the transformed state in developmentally diverse cancer cell lines and for tumor growth. There is emerging evidence that LOX-1 plays an important role in the angiogenesis process. In this review, we outline the roles of angiogenesis in atherogenesis and tumorigenesis, and describe the role of LOX-1 as a potential molecular target for blocking angiogenesis.

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Oxidized LDL binding to LOX-1 upregulates VEGF expression in cultured bovine chondrocytes through activation of PPAR-γ

Cited by 48 publications

References 32 publications

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

Angiogenesis is a Link Between Atherosclerosis and Tumorigenesis: Role of LOX-1

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