Oscillatory shear stress increases smooth muscle cell proliferation and akt phosphorylation

Haga, Masae; Yamashita, Atsuo; Paszkowiak, Jacek; Sumpio, Bauer E.; Dardik, Alan

doi:10.1016/s0741-5214(03)00329-x

Cited by 72 publications

(61 citation statements)

References 59 publications

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“…22,51 The role of PI3K in VEGF-mediated signal transduction and angiogenic responses is established. 52,53 In our present study, we confirmed that phospho-AKt increased rapidly in HASMC response to VEGF stimulation, accompanied by increased HASMC migration. Inhibition of VEGF-induced migration using Wortmannin indicated that early activation of PI3K was necessary for the SMC migration.…”

Section: Discussionsupporting

confidence: 85%

Minocycline Exerts Multiple Inhibitory Effects on Vascular Endothelial Growth Factor–Induced Smooth Muscle Cell Migration

Yao

Chen

Zhai

et al. 2004

Circulation Research

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Abstract-Widely used tetracycline antibiotics affect many cellular functions relevant to human vascular disease including cell proliferation, migration, and matrix remodeling. We examined whether minocycline inhibited human aortic smooth muscle cell (HASMC) migration induced by vascular endothelial growth factor (VEGF). After the establishment of an optimal dose, minocycline treated HASMC were exposed to VEGF. HASMC migration, matrix metalloproteinase (MMP)-2 and MMP-9 activities, mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase (PI3K) phosphorylation were determined by smooth muscle cell (SMC) invasion assay, real-time polymerase chain reaction, zymograms, and Western blot analysis, respectively. We demonstrated that VEGF and platelet-derived growth factor (PDGF)-induced SMC migration in a dose-dependent manner. MMP-9, but not MMP-2, mRNA was increased during VEGF stimulation. MMP-9 activity was increased from 1.5-to 2.5-fold in a dose-dependent manner (PϽ0.05). Both ERK1/2 and PI3K/AKt pathways were activated during VEGF-induced HASMCs migration. We then demonstrated that minocycline can inhibit VEGF-induced HASMC migration (PϽ0.05). The effects may be through the inhibition of MMP-9 mRNA transcription, protein activities and downregulation of ERK1/2 and PI3K/Akt pathway phosphorylation. Our results indicated that minocycline exerts multiple effects on VEGF-induced SMC migration, including inhibition of MMP-9 mRNA transcription and protein activities and downregulating ERK1/2 and PI3K signal pathways, suggesting minocycline may be a potentially therapeutic approach to inhibit disease process induced angiogenesis.

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Section: Discussionsupporting

confidence: 85%

Minocycline Exerts Multiple Inhibitory Effects on Vascular Endothelial Growth Factor–Induced Smooth Muscle Cell Migration

Yao

Chen

Zhai

et al. 2004

Circulation Research

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“…The proteins downstream of mTOR (S6K and 4E-BP1), however, started to return to basal levels after an initial activation. Other investigators have reported that expression of certain genes requires the activation of the PI3K-PKB-Akt-S6K pathway (27,34) and have suggested that PDK-1 is a central mediator of the cell signaling between PI3K and Akt-S6K (32). Although we have not confirmed that either Akt or PDK-1 is critical for activation of mTOR from PI3K in ECs, our preliminary results (data not shown) with vascular smooth muscle cells indicate that the addition of PI3K inhibitors could attenuate the strain-induced activation of Akt.…”

Section: Discussionmentioning

confidence: 99%

Strain-induced vascular endothelial cell proliferation requires PI3K-dependent mTOR-4E-BP1 signal pathway

Li¹,

Sumpio²

2005

American Journal of Physiology-Heart and Circulatory Physiology

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“…Oscillatory shear stress increases VSMC phenotypic transformation to the synthetic phenotype and then induces proliferation, mainly through activation of the phosphatidylinositol 3 kinase (PI3K)-protein kinase B (Akt) signal transduction pathway [32] and extracellular signal-regulated protein kinase 1/2 (ERK1/2) pathway [17] ( figure 1 and table 1). Hence, the flow pattern is another critical parameter for cell proliferation and migration.…”

Section: Haemodynamic Factors and Vascular Smoothmentioning

confidence: 99%

Biomechanical regulation of vascular smooth muscle cell functions: from in vitro to in vivo understanding

Qiu

Zheng

et al. 2014

J. R. Soc. Interface.

142

114

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Vascular smooth muscle cells (VSMCs) have critical functions in vascular diseases. Haemodynamic factors are important regulators of VSMC functions in vascular pathophysiology. VSMCs are physiologically active in the threedimensional matrix and interact with the shear stress sensor of endothelial cells (ECs). The purpose of this review is to illustrate how haemodynamic factors regulate VSMC functions under two-dimensional conditions in vitro or three-dimensional co-culture conditions in vivo. Recent advances show that high shear stress induces VSMC apoptosis through endothelial-released nitric oxide and low shear stress upregulates VSMC proliferation and migration through platelet-derived growth factor released by ECs. This differential regulation emphasizes the need to construct more actual environments for future research on vascular diseases (such as atherosclerosis and hypertension) and cardiovascular tissue engineering.

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Oscillatory shear stress increases smooth muscle cell proliferation and akt phosphorylation

Abstract: SMC directly respond to oscillatory SS by increasing DNA synthesis, proliferation, and activation of the PI3K-Akt signal transduction pathway. These results suggest a mechanism of SMC survival and proliferation in response to endothelial-denuding arterial injury.

Cited by 72 publications

References 59 publications

Minocycline Exerts Multiple Inhibitory Effects on Vascular Endothelial Growth Factor–Induced Smooth Muscle Cell Migration

Minocycline Exerts Multiple Inhibitory Effects on Vascular Endothelial Growth Factor–Induced Smooth Muscle Cell Migration

Strain-induced vascular endothelial cell proliferation requires PI3K-dependent mTOR-4E-BP1 signal pathway

Biomechanical regulation of vascular smooth muscle cell functions: from in vitro to in vivo understanding

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