Evidence for modulation of genes involved in vascular adaptation by prolonged exposure of endothelial cells to shear stress

Bongrazio, Mauro; Baumann, Clemens; Zakrzewicz, Andreas; Pries, Axel R.; Gaehtgens, P.

doi:10.1016/s0008-6363(00)00111-5

Cited by 68 publications

(54 citation statements)

References 36 publications

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“…ADAMTS1, which was significantly upregulated in the present microarray and real-time RT-PCR assays, is an extracellular matrix degrading enzyme produced in the vascular wall and induced by prolonged exposure of endothelial cells to shear stress 18) and catalyzes the proteolysis of the extracellular matrix proteins aggrecan and vesican V1, which are often expressed in atherosclerotic human aortas. 19) Further, this gene is thought to be associated with various inflammatory Vol 46 No 2 processes and angiogenesis, making it a potential culprit for aneurysmal formation.…”

Section: Discussionmentioning

confidence: 76%

Altered Patterns of Gene Expression Specific to Thoracic Aortic Aneurysms: Microarray Analysis of Surgically Resected Specimens

et al. 2005

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SUMMARYChanges in the expression levels of several genes have been described in aortic aneurysm specimens, however, the spectrum of diverse molecular alterations remains to be elucidated. We attempted to identify key molecules that modulate the pathogenesis of aortic aneurysm, using a complimentary DNA microarray carrying approximately 13,000 human genes.Segments of thoracic aortic aneurysms (TAA) and adjacent normal thoracic aortic tissues without aneurysmal changes (NTA) were obtained from 20 patients undergoing graft surgery. RNA obtained from five pairs of TAA and NTA samples was compared to determine aneurysm-specific alterations using microarray. Further, the expression levels of several genes of interest were verified in the remaining specimens by real-time reverse transcription-polymerase chain reaction (RT-PCR).In microarray assays, several types of the matrix metalloproteinases were upregulated as reported previously. Also, 220 genes suggested to be involved in protein degradation, inflammation, apoptosis, stress response, intracellular signaling, and other processes were significantly upregulated. Many of these genes have not been previously implicated in cardiovascular disease. The real time RT-PCR independently confirmed that the expression levels of MMP-2, MMP-9, ADAMTS-1, and caspase 4 were consistently increased in TAA.The results indicate that many genes are involved in a complicated manner in the pathogenesis of TAA. Investigation of these genes will help clarify the pathogenesis of this disease, and may lead to the discovery of novel therapeutic targets. (Int Heart J 2005; 46: 265-277)

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Section: Discussionmentioning

confidence: 76%

Altered Patterns of Gene Expression Specific to Thoracic Aortic Aneurysms: Microarray Analysis of Surgically Resected Specimens

et al. 2005

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“…KD R=F lk-1) and Tie2 (F igure 3). 61,65,67 VEGF R -2 is the primary mediator of the VEGF response in endothelial cells and is rapidly phosphorylated upon exposure to LSS. 146 It is required for endothelial cell differentiation from angioblast precursors and has also been implicated in endothelial survival during physiological stress.…”

Section: The Mitigation Of Oxidant Stress and In Ammation By Lssmentioning

confidence: 99%

Adaptation of the endothelium to fluid flow: in vitro analyses of gene expression and in vivo implications

Wasserman

Topper

2004

Vasc Med

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Biomechanical forces generated by blood ow play an important role in the pathogenesis of vascular disease. For example, regions exposed to non-uniform shear stresses develop early atherosclerotic lesions while areas exposed to uniform shear stresses are protected. A variety of in vitro ow apparatuses have been created to apply well-characterized ow patterns to endothelial cells in an effort to dissect the cellular and molecular pathways involved in these distinct processes. Recent advances in biotechnology have permitted large-scale transcriptional pro ling techniques to replace candidate gene screens and have allowed the genome-wide examination of biomechanical force-induced endothelial gene expression pro les. This review provides an overview of biomechanical force-induced modulation of endothelial phenotype. It examines the effect of sustained laminar shear stress (LSS), a type of uniform shear stress, on in vitro endothelial gene expression by synthesizing data from the early candidate gene and differential display polymerase chain reaction (PCR) approaches to the numerous, recent, high throughput functional genomic analyses. These studies demonstrate that prolonged LSS regulates the expression of only a small percentage ( 1¡5%) of endothelial genes, and this transcriptional pro le produces an endothelial phenotype that is quiescent, being protected from apoptosis, in ammation and oxidative stress. These observations provide a possible molecular mechanism for the strong correlation between patterns of blood ow and the occurrence of vascular pathologies, such as atherosclerosis, in vivo.

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“…Une publication récente révèle la régulation biomécanique de 52 gènes dans des cellules endothéliales de veine ombilicale en culture (HUVEC): le cytochrome p450 et le transporteur prostaglandine sont parmi les plus puissamment stimulés, alors que le CTGF (connective tissue growth factor), l'endothéline-1 et le MCP (monocyte chemotactic protein) sont parmi les plus fortement inhibés [28]. Dans les HUVEC, M. Bongrazio et al ont démontré l'activation de 20 gènes (dont la métalloprotéase METH-1) et l'inhibition de 13 gènes, dont l'angiopoïétine 2 et le GAS3 (growth-arrest specific gene 3), par la contrainte de cisaillement [29]. Une troisième étude décrit la surexpression de la métallo-protéase-1, et des récepteurs de l'angiopoïétine (Tie-2) et du VEGF (FLK-1) dans des cellules endothéliales aortiques humaines soumises à un flux laminaire, et la réduction simultanée de l'expression de gènes codant pour des protéines impliquées dans l'inflammation et la prolifération [30].…”

Section: Facteurs Mécaniques Et Profil D'expression Des Gènes Dans Leunclassified

Bases cellulaires de la mécanotransduction dans la cellule endothéliale

Lehoux

Tedgui

2004

Med Sci (Paris)

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Evidence for modulation of genes involved in vascular adaptation by prolonged exposure of endothelial cells to shear stress

Abstract: Since angiopoietin-2 and METH-1 are known to be involved in vessel regression/stabilization, the reported modulation of these genes by prolonged shear stress exposure strongly suggests their participation in flow-dependent vascular adaptation.

Cited by 68 publications

References 36 publications

Altered Patterns of Gene Expression Specific to Thoracic Aortic Aneurysms: Microarray Analysis of Surgically Resected Specimens

Altered Patterns of Gene Expression Specific to Thoracic Aortic Aneurysms: Microarray Analysis of Surgically Resected Specimens

Adaptation of the endothelium to fluid flow: in vitro analyses of gene expression and in vivo implications

Bases cellulaires de la mécanotransduction dans la cellule endothéliale

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