Osteopontin: A major player on hypertension-induced vascular remodeling

Brás, Lisandra E. de Castro

doi:10.1016/j.yjmcc.2015.05.020

Cited by 7 publications

(7 citation statements)

References 30 publications

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“…This highlights the therapeutic potential of the αAnalogue when given in established hypertension. Although the αAnalogue was unable to reduce vascular endothelial dysfunction, it reduced markers of damage such as osteopontin, the downstream regulator of Akt activity, 47 remodeling, fibrosis, and oxidative stress. 7 The αAnalogue reduced both vascular and cardiac NOX-2 expression.…”

Section: Discussionmentioning

confidence: 94%

A Novel α-Calcitonin Gene-Related Peptide Analogue Protects Against End-Organ Damage in Experimental Hypertension, Cardiac Hypertrophy, and Heart Failure

et al. 2017

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Section: Discussionmentioning

confidence: 94%

A Novel α-Calcitonin Gene-Related Peptide Analogue Protects Against End-Organ Damage in Experimental Hypertension, Cardiac Hypertrophy, and Heart Failure

et al. 2017

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“…Furthermore, OPN was reported to be strongly expressed in a synthetic VSMC phenotype [15], and suggested to be a key factor of the development of vascular remodeling diseases [16,17]. Although the vascular remodeling effects of OPN have aroused considerable research interest [18], little is known of its role in vascular wall remodeling.…”

Section: Introductionmentioning

confidence: 99%

α-Iso-Cubebene Inhibits PDGF-Induced Vascular Smooth Muscle Cell Proliferation by Suppressing Osteopontin Expression

et al. 2017

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α-Iso-cubebene (ICB) is a dibenzocyclooctadiene lignin contained in Schisandra chinensis (SC), a well-known medicinal herb that ameliorates cardiovascular symptoms. Thus, we examined the effect of ICB on vascular smooth muscle cell (VSMC) proliferation, a key feature of diverse vascular diseases. When VSMCs primary cultured from rat thoracic aorta were stimulated with PDGF (1–10 ng/ml), cell proliferation and osteopontin (OPN) expression were concomitantly up-regulated, but these effects were attenuated when cells were treated with MPIIIB10, a neutralizing monoclonal antibody for OPN. In aortic tissues exposed to PDGF, sprouting VSMC numbers increased, which was attenuated in tissues from OPN-deficient mice. Furthermore, VSMC proliferation and OPN expression induced by PDGF were attenuated dose-dependently by ICB (10 or 30 μg/ml). Reporter assays conducted using OPN promoter-luciferase constructs showed that the promoter region 538–234 bp of the transcription start site was responsible for transcriptional activity enhancement by PDGF, which was significantly inhibited by ICB. Putative binding sites for AP-1 and C/EBPβ in the indicated promoter region were suggested by TF Search, and increased binding of AP-1 and C/EBPβ in PDGF-treated VSMCs was demonstrated using a ChIP assay. The increased bindings of AP-1 and C/EBPβ into OPN promoter were attenuated by ICB. Moreover, the PDGF-induced expression of OPN was markedly attenuated in VSMCs transfected with siRNA for AP-1 and C/EBPβ. These results indicate that ICB inhibit VSMC proliferation by inhibiting the AP-1 and C/EBPβ signaling pathways and thus downregulating OPN expression.

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“…OPN played an important role in vascular disease and in the response to vascular injury by stimulating VSMC migration, proliferation, and ECM synthesis, demonstrating a major role in hypertension-induced vascular remodeling. 25) Mechanical stretch induced OPN expression in VSMC and increased OPN promoter activity. Mechani-cal stretch-induced MMP-2 production was attenuated in cells treated with OPN siRNA or anti-OPN antibody as well as in OPN-deficient VSMC cultured from aorta of OPN deficient mice, 26) further indicating a crucial role of OPN in vascular remodeling.…”

Section: Discussionmentioning

confidence: 98%

Osteopontin in the Pathogenesis of Aortic Dissection by the Enhancement of MMP Expressions

Fan

Zhou

et al. 2019

Int. Heart J.

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The pathogenesis of aortic dissection (AD) is unclear. The aim of this study was to explore the relationship between osteopontin (OPN) and AD. Fifty AD patients were enrolled; 29 had hypertension with AD (H-AD) and 21 no hypertension with HD (NH-AD). Twenty-five healthy controls (NH-C) and 14 patients with hypertension (H-C) were also enrolled. Serum and aortic wall OPN levels were determined. Human vascular muscle cells (HVSMC) were stimulated by both low (1 μg/mL) and high (5 μg/mL) concentrations of OPN and cell proliferation as well as apoptosis was measured. Transforming growth factor-β (TGF-β), matrix metalloproteinase 1 (MMP-1), MMP-2, MMP-9, TIMP-1, and TIMP-2 gene expressions by HVSMC were measured and Akt, IκB, Smad1/5/8 and Erk1/2 signaling pathways were detected. Our results showed that AD patients demonstrated significantly higher levels of serum and local OPN expressions compared to healthy controls. In those with hypertension, the serum concentrations of OPN were increased compared to those without hypertension. In in vitro culture, a high dose of OPN stimulation promoted the proliferation of HVSMC but did not affect cell apoptosis. Both concentrations of OPN enhanced MMP-2 gene expression and its activity in HVSMC. Moreover, Akt and IκB signaling pathways were significantly activated after OPN stimulation while the Smad1/5/8 and Erk1/2 signaling pathways were not changed. The addition of an IκB inhibitor significantly abrogated MMP-2 gene expression. Our data show that OPN may participate in the pathogenesis of AD by the enhancement of MMP-2 expression.

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Osteopontin: A major player on hypertension-induced vascular remodeling

Cited by 7 publications

References 30 publications

A Novel α-Calcitonin Gene-Related Peptide Analogue Protects Against End-Organ Damage in Experimental Hypertension, Cardiac Hypertrophy, and Heart Failure

A Novel α-Calcitonin Gene-Related Peptide Analogue Protects Against End-Organ Damage in Experimental Hypertension, Cardiac Hypertrophy, and Heart Failure

α-Iso-Cubebene Inhibits PDGF-Induced Vascular Smooth Muscle Cell Proliferation by Suppressing Osteopontin Expression

Osteopontin in the Pathogenesis of Aortic Dissection by the Enhancement of MMP Expressions

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