Shear stress influences the release of platelet derived growth factor and basic fibroblast growth factor by arterial smooth muscle cells

Sterpetti, Antonio V.; Cucina, Alessandra; Fragale, Alessandra; Lepidi, Sandro; Cavallaro, Antonino; Santoro-D'Angelo, Luciana

doi:10.1016/s0950-821x(05)80448-7

Cited by 46 publications

(27 citation statements)

References 14 publications

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“…Affinity modulation of FGFRs has been shown to occur in cultured vascular SMCs. 25 A previous study 26 has shown that shear stress can influence the release of growth factors, such as FGF-2 and platelet-derived growth factor, which is in agreement with our results. However, that study did not consider the possibility of cell loss or detachment on flow (which apparently occurred in their system) as the source of released FGF-2.…”

Section: Discussionsupporting

confidence: 93%

Fluid Flow Releases Fibroblast Growth Factor-2 From Human Aortic Smooth Muscle Cells

Rhoads

Eskin

McIntire

2000

ATVB

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Abstract-This study tested the hypothesis that fluid shear stress regulates the release of fibroblast growth factor (FGF)-2 from human aortic smooth muscle cells. FGF-2 is a potent mitogen that is involved in the response to vascular injury and is expressed in a wide variety of cell types. FGF-2 is found in the cytoplasm of cells and outside cells, where it associates with extracellular proteoglycans. To test the hypothesis that shear stress regulates FGF-2 release, cells were exposed to flow, and FGF-2 amounts were measured from the conditioned medium, pericellular fraction (extracted by heparin treatment), and cell lysate. Results from the present study show that after 15 minutes of shear stress at 25 dyne/cm 2 in a parallel-plate flow system, a small but significant fraction (17%) of the total FGF-2 was released from human aortic smooth muscle cells. FGF-2 levels in the circulating medium increased 10-fold over medium from static controls (PϽ0.01). A 50% increase in FGF-2 content versus control (PϽ0.01) was found in the pericellular fraction (extracted by heparin treatment). Furthermore, a significant decrease in FGF-2 was detected in the cell lysate, indicating that FGF-2 was released from inside the cell. Cell permeability studies with fluorescent dextran were performed to examine whether transient membrane disruption caused FGF-2 release. Flow cytometry detected a 50% increase in mean fluorescence of cells exposed to 25 dyne/cm 2 versus control cells. This indicates that the observed FGF-2 release from human aortic smooth muscle cells is likely due to transient membrane disruption on initiation of flow. Key Words: shear stress Ⅲ fibroblast growth factor-2 Ⅲ vascular smooth muscle A fter vascular injury, it is believed that regions of denuded endothelium directly expose underlying smooth muscle cells (SMCs) to blood flow. 1 Consequently, SMCs can experience fluid shear stress that may alter their biological properties. Previous work has shown that flow decreases the proliferation of cultured human aortic SMCs (hASMCs) 2 and increases the production of nitric oxide (NO) by these cells. 3 Furthermore, fluid dynamic models of intact blood vessels suggest that SMCs normally experience shear stress as a result of interstitial flow driven by transmural pressure gradients. 4 Fibroblast growth factor (FGF)-2 is a potent mitogen for SMCs and endothelial cells (ECs). FGF-2 is expressed ubiquitously in the basement membranes of normal human blood vessels 5 and on the apical surface of cultured ECs. 6 FGF-2 exists in several molecular weight isoforms generated by the initiation of translation at alternate upstream CUG codons. 7 The 18-kDa molecular mass form is found mainly in the cytoplasm, whereas higher molecular mass forms (22 to 24 kDa) are found in the nucleus. The biological activity of FGF-2 is mediated through interaction with specific highaffinity cell surface FGF receptors (FGFRs). 8 There are 4 members in the FGFR family, and among these, FGFR-1 is the predominant form expressed by arterial SMCs. 9 Studies ...

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Section: Discussionsupporting

confidence: 93%

Fluid Flow Releases Fibroblast Growth Factor-2 From Human Aortic Smooth Muscle Cells

Rhoads

Eskin

McIntire

2000

ATVB

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“…6 Conversely, relative elevations of blood flow and shear stress appear to have an atheroprotective role and inhibit intimal thickening after vascular injury. [7][8][9] Hemodynamic forces have been shown to modulate endothelial and vascular smooth muscle cell (VSMC) responses, which involve the induction of cytokines, such as platelet-derived growth factor (PDGF), basic fibroblast growth factor, and transforming growth factor-␤1 (TGF-␤1), 10,11 in addition to other mediators, such as nitric oxide, 7 tissue plasminogen activator, 12,13 and matrix metalloproteinases (MMPs), 1 4 involved in vascular remodeling.…”

mentioning

confidence: 99%

Increased Flow and Shear Stress Enhance In Vivo Transforming Growth Factor-β1 After Experimental Arterial Injury

Song

Kocharyan

Fortunato

et al. 2000

ATVB

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Abstract-We have previously demonstrated that high-flow (HF) conditions inhibit experimental intimal hyperplasia.We hypothesized that such flow conditions may alter transforming growth factor-␤1 (TGF-␤1) after mural injury. The right common carotid artery (CCA) was balloon-injured in 54 New Zealand White male rabbits. Flow was thereafter preserved (normal flow [NF]), reduced by partial outflow occlusion (low flow [LF]), or increased by ligation of the left CCA (HF). Four sham-operated animals served as uninjured controls. Mean blood flow and pressure in the right CCA were measured before and after flow modulation and before euthanasia (3, 7, and 14 days). TGF-␤1 mRNA and protein levels in the right CCA were determined by Northern and ELISA analyses at each time point. At 7 and 14 days, intimal hyperplasia was quantified, and the transmural localization of TGF-␤1 was determined by immunohistochemical analysis. Mean flow was reduced from 22Ϯ1 to 10Ϯ3 mL/min in the LF group and increased to 34Ϯ2 mL/min in the HF group (PϽ0.001). Blood pressure was not different among the flow groups for all time points. Wall shear stress was markedly decreased in the LF group to 14Ϯ4 dyne/cm 2 and increased in the HF group to 63Ϯ6 dyne/cm 2 at 7 days compared with values in uninjured controls (39Ϯ2 dyne/cm 2 , PϽ0.001) and the NF group (44Ϯ7 dyne/cm 2 , PϽ0.001). At 14 days, wall shear stress was similar among the flow groups. The intima-to-media ratio was 5-and 2-fold greater in the LF group than in the HF and NF groups at 14 days. mRNA levels for TGF-␤1 and its active ligand were increased in the HF group by at least 2-and 3-fold, respectively, at 3 and 7 days compared with levels in uninjured controls and the LF group (PϽ0.05) but were not different among the flow groups at 14 days. TGF-␤1 preferentially localized in the abluminal vascular smooth muscle cells of the HF arterial segments. Flow-and shear-mediated release of TGF-␤1 may therefore play a role in abrogating the proliferative and migratory response of vascular smooth muscle cells in the early stages after mural injury.

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“…[8][9][10]21,23) bFGF production increases under certain pathological conditions 9) and may prevent neuronal injury. A number of studies have shown the protective effect of bFGF in cerebral ischemia.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the level of bFGF in bovine aortic SMCs is proportional to the amount of shear stress applied to endothelial cells, suggesting that a hemodynamic factor is a possible regulator of bFGF synthesis. 21) If this relationship was to exist in cerebral arterioles, vascular bFGF production may regulate rCBF in conjunction with hemodynamic conditions. Extraluminal application of bFGF caused vasodilation accompanied by membrane hyperpolarization.…”

Section: Discussionmentioning

confidence: 99%

Vasodilatory Effect of Basic Fibroblast Growth Factor in Isolated Rat Cerebral Arterioles: Mechanisms Involving Nitric Oxide and Membrane Hyperpolarization.

Kajita

Takayasu²,

Yoshida³

et al. 2001

Neurol. Med. Chir.(Tokyo)

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Basic fibroblast growth factor (bFGF), a potent mitogen, acutely dilates cerebral blood vessels and may be effective in reducing cerebral infarction. However, the vasodilatory mechanism, which may involve nitric oxide (NO), is not completely understood. This study investigated whether membrane hyperpolarization is also involved in this mechanism. Membrane potential (MP) of smooth muscle cells and vessel diameter of isolated intracerebral arterioles were simultaneously measured following extraluminal application of bFGF in rats. The involvement of NO and adenosine triphosphate-sensitive potassium (K ATP ) channels in bFGF-induced vasodilation and membrane hyperpolarization was evaluated using specific inhibitors, N G -monomethyl-L-arginine (L-NMMA, 10 -4 M) and glibenclamide (GB, 10 -5 M), respectively. The resting MP was recorded at a mean value of -31.9 ± 4.5 mV. bFGF (1 to 1000 ng/ml) produced significant vasodilation and hyperpolarization. Treatment with L-NMMA caused vasoconstriction and significantly attenuated bFGF-induced vasodilation without affecting membrane hyperpolarization. In the presence of GB, the membrane potential was significantly depolarized but the vessel diameter was only marginally reduced, so bFGF-induced membrane hyperpolarization was inhibited while arteriolar dilation was attenuated. These results suggest that bFGF-induced vasodilation is mediated by a mechanism involving both NO and membrane hyperpolarization, and that membrane hyperpolarization is caused by the activation of K ATP channels.

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Shear stress influences the release of platelet derived growth factor and basic fibroblast growth factor by arterial smooth muscle cells

Abstract: Increasing shear stress promotes the release of both PDGF and bFGF from arterial SMC in culture and is a possible explanation for atherosclerosis formation.

Cited by 46 publications

References 14 publications

Fluid Flow Releases Fibroblast Growth Factor-2 From Human Aortic Smooth Muscle Cells

Fluid Flow Releases Fibroblast Growth Factor-2 From Human Aortic Smooth Muscle Cells

Increased Flow and Shear Stress Enhance In Vivo Transforming Growth Factor-β1 After Experimental Arterial Injury

Vasodilatory Effect of Basic Fibroblast Growth Factor in Isolated Rat Cerebral Arterioles: Mechanisms Involving Nitric Oxide and Membrane Hyperpolarization.

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