Different Effects of High and Low Shear Stress on Platelet-Derived Growth Factor Isoform Release by Endothelial Cells

Hemodynamic forces have an important role in venous intimal hyperplasia, which is the main cause of arteriovenous fistula dysfunction. Endothelial cells (ECs) constantly exposed to the shear stress of blood flow, converted the mechanical stimuli into intracellular signals, and interacted with the underlying vascular smooth muscle cells (VSMCs). Caveolin-1 is one of the important mechanoreceptors on cytomembrane, which is related to vascular abnormalities. Extracellular signal-regulated kinase1/2 (ERK1/2) pathway is involved in the process of VSMCs proliferation and migration. In the present study, we explore the effects of Caveolin-1-ERK1/2 pathway and uremia toxins on the endothelial cells and VSMCs following shear stress application. Different shear stress was simulated with a ECs/VSMCs cocultured parallel-plate flow chamber system. Low shear stress and oscillating shear stress up-regulated the expression of fibroblast growth factor-4, platelet-derived growth factor-BB, vascular endothelial growth factor-A, ERK1/2 phosphorylation in endothelial cells, and proliferation and migration of VSMCs but down-regulated the Caveolin-1 expression in endothelial cells. Uremia toxin induces the proliferation and migration of VSMCs but not in a Caveolin-1-dependent manner in the static environment. Low shear stress-induced proliferation and migration of VSMCs is inhibited by Caveolin-1 overexpression and ERK1/2 suppression. Shear stress-regulated VSMC proliferation and migration is an endothelial cells-dependent process. Low shear stress and oscillating shear stress exert atherosclerotic influences on endothelial cells and VSMCs. Low shear stress modulated proliferation and migration of VSMCs through Caveolin-1-ERK1/2 pathway, which suggested that Caveolin-1 and ERK1/2 can be used as a new therapeutic target for the treatment of arteriovenous fistula dysfunction. Impact statement Venous intimal hyperplasia is the leading cause of arteriovenous fistula (AVF) dysfunction. This article reports that shear stress-regulated vascular smooth muscle cells (VSMCs) proliferation and migration is an endothelial cell (EC)-dependent process. Low shear stress (LSS) and oscillating shear stress (OSS) exert atherosclerotic influences on the ECs and VSMCs. LSS-induced proliferation and migration of VSMCs is inhibited by Caveolin-1 overexpression and extracellular signal-regulated kinase1/2 (ERK1/2) suppression, which suggested that Caveolin-1 and ERK1/2 can be used as a new therapeutic target for the treatment of AVF dysfunction.

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Restoration of endothelial autophagic flux in vascular endothelial cells exposed to low shear stress reduces atherosclerotic lesions

Archives of Cardiovascular Diseases Supplements ◽

10.1016/j.acvdsp.2021.04.078 ◽

2021 ◽

Vol 13 (2) ◽

pp. 177

Author(s):

S. Chatterjee ◽

M. Kheloufi ◽

S. Mazlan ◽

X. Loyer ◽

T. Mckinsey ◽

...

Keyword(s):

Endothelial Cells ◽

Shear Stress ◽

Vascular Endothelial Cells ◽

Autophagic Flux ◽

Vascular Endothelial ◽

Atherosclerotic Lesions ◽

Low Shear Stress ◽

Low Shear

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Low Shear Stress Upregulates CX3CR1 Expression by Inducing VCAM-1 via the NF-κB Pathway in Vascular Endothelial Cells

Cell Biochemistry and Biophysics ◽

10.1007/s12013-020-00931-4 ◽

2020 ◽

Vol 78 (3) ◽

pp. 383-389 ◽

Cited By ~ 1

Author(s):

Yiwei Zhao ◽

Peile Ren ◽

Qiufang Li ◽

Shafiu Adam Umar ◽

Tan Yang ◽

...

Keyword(s):

Endothelial Cells ◽

Shear Stress ◽

Protein Expression ◽

Vascular Endothelial Cells ◽

Critical Role ◽

Mrna Levels ◽

Vascular Endothelial ◽

Low Shear Stress ◽

Low Shear ◽

Cx3cr1 Expression

Abstract Atherosclerosis is a significant cause of mortality and morbidity. Studies suggest that the chemokine receptor CX3CR1 plays a critical role in atherogenesis. Shear stress is an important mechanical force that affects blood vessel function. In this study, we investigated the effect of shear stress on CX3CR1 expression in vascular endothelial cells (VECs). First, cells were exposed to different shear stress and then CX3CR1 mRNA and protein were measured by quantitative RT-PCR and western blot analysis, respectively. CX3CR1 gene silencing was used to analyze the molecular mechanisms underlying shear stress-mediated effects on CX3CR1 expression. CX3CR1 mRNA and protein expression were significantly increased with 4.14 dyne/cm2 of shear stress compared with other tested levels of shear stress. We observed a significant increase in CX3CR1 mRNA levels at 2 h and CX3CR1 protein expression at 4 h. CX3CR1-induced VCAM-1 expression in response to low shear stress by activating NF-κB signaling pathway in VECs. Our findings demonstrate that low shear stress increases CX3CR1 expression, which increases VCAM-1 expression due to elevated NF-κB activation. The current study provides evidence of the correlation between shear stress and atherosclerosis mediated by CX3CR1.

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Shear stress increases endothelial platelet-derived growth factor mRNA levels

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1991.260.2.h642 ◽

1991 ◽

Vol 260 (2) ◽

pp. H642-H646 ◽

Cited By ~ 20

Author(s):

H. J. Hsieh ◽

N. Q. Li ◽

J. A. Frangos

Keyword(s):

Endothelial Cells ◽

Shear Stress ◽

Growth Factor ◽

Umbilical Vein ◽

Fold Increase ◽

Platelet Derived Growth Factor ◽

Mrna Levels ◽

Cell Mitogen ◽

Stress Dependent

We have investigated the effect of shear stress on platelet-derived growth factor (PDGF) A and B chain mRNA levels in cultured human umbilical vein endothelial cells (hUVEC). The levels of both PDGF A and B mRNA in hUVEC were increased by a physiological shear stress (16 dyn/cm2), reaching a maximum approximately 1.5-2 h after the onset of shear stress and returning almost to control values at 4 h. The peak levels showed a more than 10-fold enhancement for PDGF A mRNA and a 2- to 3-fold increase for PDGF B mRNA (P less than 0.05). PDGF A mRNA also showed a shear-dependent increase from 0 to 6 dyn/cm2 (P less than 0.05) and then plateaued from 6 to 51 dyn/cm2. PDGF B mRNA levels were elevated as shear stress increased from 0 to 6 dyn/cm2 then declined gradually to a minimum at 31 dyn/cm2 (P less than 0.05) and increased again when shear stress rose to 51 dyn/cm2 (P less than 0.05). PDGF, a potent smooth muscle cell mitogen and vasoconstrictor, released from the endothelium may regulate the blood flow in vivo. The shear stress-dependent elevation of PDGF A and B mRNA in endothelial cells may be involved in the adaptation of blood vessels to flow mediated by the endothelium.

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Low shear stress up-regulation of proinflammatory gene expression in human retinal microvascular endothelial cells

Experimental Eye Research ◽

10.1016/j.exer.2013.10.001 ◽

2013 ◽

Vol 116 ◽

pp. 308-311 ◽

Cited By ~ 12

Author(s):

Akihiro Ishibazawa ◽

Taiji Nagaoka ◽

Harumasa Yokota ◽

Shinji Ono ◽

Akitoshi Yoshida

Keyword(s):

Gene Expression ◽

Endothelial Cells ◽

Shear Stress ◽

Microvascular Endothelial Cells ◽

Low Shear Stress ◽

Proinflammatory Gene ◽

Microvascular Endothelial ◽

Proinflammatory Gene Expression ◽

Low Shear

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Fluid shear stress stimulates platelet-derived growth factor expression in endothelial cells

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1993.265.1.h3 ◽

1993 ◽

Vol 265 (1) ◽

pp. H3-H8 ◽

Cited By ~ 15

Author(s):

M. Mitsumata ◽

R. S. Fishel ◽

R. M. Nerem ◽

R. W. Alexander ◽

B. C. Berk

Keyword(s):

Endothelial Cells ◽

Shear Stress ◽

Growth Factor ◽

Fluid Shear Stress ◽

Critical Role ◽

Fold Increase ◽

Flow Chamber ◽

Platelet Derived Growth Factor ◽

Aortic Endothelial Cells ◽

A Chain

Fluid flow and the associated shear stress play a critical role in vascular growth and remodeling. Recent data suggest that increased endothelial cell expression of platelet-derived growth factor (PDGF) A- and B-chain by flow may participate in these events. In the present study, we examined the mechanism for flow-induced PDGF expression, focusing on protein kinase C (PKC). Bovine aortic endothelial cells were exposed to flow (shear stress = 30 dyn/cm2) in a parallel-plate flow chamber. Increases in PDGF B-chain, but not PDGF A-chain, were observed within 3 h, maximal within 6 h (13-fold increase), and sustained for 24 h. PKC appeared to be involved because phorbol 12-myristate 13-acetate induced PDGF B-chain mRNA. Activation of PKC alone, however, was insufficient to induce PDGF mRNA because the selective PKC activator, 1-oleoyl-2-acetyl-sn-glycerol, did not induce PDGF expression. A PKC-independent pathway was suggested by the fact that inhibition of PKC (downregulation with phorbol 12,13-dibutyrate or exposure to staurosporine) failed to block PMA or flow-induced PDGF B-chain expression. These results demonstrate flow-induced PDGF B-chain expression in endothelial cells that appears to be mediated, in part, by a PKC-independent pathway.

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