Pattern formation of vascular smooth muscle cells subject to nonuniform  fluid shear stress: role of PDGF-β receptor and Src

Liu, Shu Q.; Tieché, Christopher; Tang, Dalin; Alkema, Paul K.

doi:10.1152/ajpheart.00434.2003

Cited by 21 publications

(18 citation statements)

References 68 publications

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“…The current investigation confirms and extends the findings of Liu et al (23)(24)(25)(26) and validates our previous computational results (18,20,21). The current results demonstrate that time-dependent neointimal hyperplasia occurred in regions displaying the lowest initial values of WSS predicted by 3-D CFD modeling of a theoretical artery.…”

Section: Discussionsupporting

confidence: 92%

“…Neointimal hyperplasia, the spatial clustering of cells, and expression of several molecular mediators of proliferation were observed at stagnation points and in regions of low WSS along the cylinder. In contrast, these findings were absent in areas of elevated shear stress along the cylinder and after pharmacological inhibition of cellular proliferation (24,25). These findings suggested that neointimal hyperplasia occurs in regions of low WSS in vivo.…”

Section: Discussionmentioning

confidence: 99%

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Alterations in wall shear stress predict sites of neointimal hyperplasia after stent implantation in rabbit iliac arteries

LaDisa¹,

Olson²,

Molthen³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

149

118

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Rates of restenosis vary with stent geometry, but whether stents affect spatial and temporal distributions of wall shear stress (WSS) in vivo is unknown. We tested the hypothesis that alterations in spatial WSS after stent implantation predict sites of NH in rabbit iliac arteries. Antegrade iliac artery stent implantation was performed under angiography, and blood flow was measured before casting 14 or 21 days after implantation. Iliac artery blood flow domains were obtained from three-dimensional microfocal X-ray computed tomography imaging and reconstruction of the arterial casts. Indexes of WSS were determined using three-dimensional computational fluid dynamics. Vascular histology was unchanged proximal and distal to the stent. Time-dependent NH was localized within the stented region and was greatest in regions exposed to low WSS and acute elevations in spatial WSS gradients. The lowest values of WSS spatially localized to the stented area of a theoretical artery progressively increased after 14 and 21 days as NH occurred within these regions. This NH abolished spatial disparity in distributions of WSS. The results suggest that stents may introduce spatial alterations in WSS that modulate NH in vivo.computational fluid dynamics; restenosis; computational modeling; computed tomography; image reconstruction; wall shear stress RESTENOSIS after stent implantation remains a persistent clinical problem (1,6,8,28,40,45). The mechanisms of restenosis are incompletely understood, but direct endothelial and smooth muscle cell damage, reduced compliance, and alterations in the distributions of wall shear stress (WSS) within the stented region have been implicated as potential triggering events that stimulate neointimal hyperplasia (11,19,44,47). Vascular damage to the vessel during implantation may be minimized by using an appropriate stent-to-artery deployment ratio (11,46). The rigid framework of the stent causes differences in compliance between the stented and native regions of the artery, but this stent rigidity provides structural scaffolding that is associated with reduced restenosis rates compared with angioplasty alone (4,8). Novel stent designs that reduce compliance mismatch at the proximal and distal edges of the stent have also been developed (2). Previous studies have suggested that there may be a correlation between stent-induced alterations in WSS and neointimal hyperplasia during pathological processes including primary atherogenesis and restenosis after angioplasty (17,18,20,21,30). However, few studies have examined detailed time-and space-dependent distributions of WSS or attempted to correlate these alterations in WSS with neointimal hyperplasia after stent implantation in vivo. Moreover, it is well known that restenosis varies with stent geometry (11,32,35,50), but the geometric influence of stent properties on spatial and temporal WSS patterns has not been thoroughly investigated. Thus we tested the hypothesis that local alterations in spatial WSS associated with stent implantation temporally pr...

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Alterations in wall shear stress predict sites of neointimal hyperplasia after stent implantation in rabbit iliac arteries

LaDisa¹,

Olson²,

Molthen³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

149

118

View full text Add to dashboard Cite

show abstract

“…Experimental results demonstrate that vascular endothelial growth factor (VEGF) receptors existed in the SMCs and that VEGF can induce SMC migration in vitro. 15,16 SMC migration was regulated by insulin-like growth factor-I, 17 PDGF, 18 basic fibroblast growth factor, 19 etc. However, the precise molecular mechanisms of regulating SMC migration are still unknown.…”

mentioning

confidence: 99%

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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“…Vasculoprotective laminar flow inhibits SMC proliferation and migration (34) by down-regulating platelet-derived growth factor and by promoting the autocrine effect of transforming growth factor-␤, a potent SMC proliferation suppressor (35). Conversely, low ESS promotes SMC proliferation and migration, independently of the effect on endothelial cells (36). Effect of low ESS on SMC phenotype.…”

Section: Role Of Low Ess In the Pathobiology Of Restenosismentioning

confidence: 99%

Role of Endothelial Shear Stress in Stent Restenosis and Thrombosis

Koskinas

Chatzizisis

Antoniadis

et al. 2012

Journal of the American College of Cardiology

267

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Restenosis and thrombosis are potentially fatal complications of coronary stenting with a recognized multifactorial etiology. The effect of documented risk factors, however, cannot explain the preponderance of certain lesion types, stent designs, and implantation configurations for the development of these complications. Local hemodynamic factors, low endothelial shear stress (ESS) in particular, are long known to critically affect the natural history of atherosclerosis. Increasing evidence now suggests that ESS may also contribute to the development of restenosis and thrombosis upon stenting of atherosclerotic plaques, in conjunction with well-appreciated risk factors. In this review, we present in vivo and mechanistic evidence associating ESS with the localization and progression of neointimal hyperplasia and in-stent clotting. Clinical studies have associated stent design features with the risk of restenosis. Importantly, computational simulations extend these observations by directly linking specific stent geometry and positioning characteristics with the post-stenting hemodynamic milieu and with the stent's thrombogenicity and pro-restenotic potential, thereby indicating ways to clinical translation. An enhanced understanding of the pathophysiologic role of ESS in restenosis and thrombosis might dictate hemodynamically favorable stent designs and deployment configurations to reduce the potential for late lumen loss and thrombotic obstruction. Recent methodologies for in vivo ESS profiling at a clinical level might allow for early identification of patients at high risk for the development of restenosis or thrombosis and might thereby guide individualized, risk-tailored treatment strategies to prevent devastating complications of endovascular interventions.

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Pattern formation of vascular smooth muscle cells subject to nonuniform fluid shear stress: role of PDGF-β receptor and Src

Cited by 21 publications

References 68 publications

Alterations in wall shear stress predict sites of neointimal hyperplasia after stent implantation in rabbit iliac arteries

Alterations in wall shear stress predict sites of neointimal hyperplasia after stent implantation in rabbit iliac arteries

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

Role of Endothelial Shear Stress in Stent Restenosis and Thrombosis

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