Fluid shear stress and the vascular endothelium: for better and for worse

Resnick, Nitzan; Yahav, Hava; Shay-Salit, Ayelet; Shushy, Moran; Schubert, Shay; Zilberman, Limor Chen Michal; Wofovitz, Efrat

doi:10.1016/s0079-6107(02)00052-4

Cited by 495 publications

(424 citation statements)

References 149 publications

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“…Shear stress regulates vascular development in the embryo and vascular tone, arteriogenesis and angiogenesis in the adult (Resnick et al, 2003). This hemodynamic stimulus activates numerous mechanoreceptors on the endothelium such as integrins, G protein-coupled receptors, cell adhesion molecules, ion channels and receptor tyrosine kinases (Chien, 2007).…”

Section: Introductionmentioning

confidence: 99%

p38 MAPK activity is stimulated by vascular endothelial growth factor receptor 2 activation and is essential for shear stress‐induced angiogenesis

Gee

Milkiewicz

Haas

2009

Journal Cellular Physiology

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Increased capillary shear stress induces angiogenesis in skeletal muscle, but the signaling mechanisms underlying this response are not known. We hypothesize that shear stress-dependent activation of vascular endothelial growth factor receptor 2 (VEGFR2) causes p38 and ERK1/2 phosphorylation, which contribute to shear stress-induced angiogenesis. Skeletal muscle microvascular endothelial cells were sheared (12 dynes/cm 2 , 0.5-24 hours). VEGFR2-Y1214 phosphorylation increased in response to elevated shear stress and VEGF stimulation. p38 and ERK1/2 phosphorylation increased at 2 hours of shear stress, but only p38 remained phosphorylated at 6 and 24 hours of shear stress. VEGFR2 inhibition abrogated p38, but not ERK1/2 phosphorylation. VEGF production was increased in response to shear stress at 6 hours, and this increased production was abolished by p38 inhibition. Male Sprague-Dawley rats were administered prazosin (50 mg/L drinking water, 1, 2, 4 or 7 days) to induce chronically elevated capillary shear stress in skeletal muscle. In some experiments, mini-osmotic pumps were used to dispense p38 inhibitor SB203580 or its inactive analog SB202474, to the extensor digitorum longus (EDL) of control and prazosin treated rats. Immunostaining and Western blotting showed increases in p38 phosphorylation in capillaries from rats treated with prazosin for 2 days but returned to basal levels at 4 and 7 days. p38 inhibition abolished the increase in capillary to muscle fibre ratio seen after 7 days of prazosin treatment. Our data suggest that p38 activation is necessary for shear stress-dependent angiogenesis.

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Section: Introductionmentioning

confidence: 99%

p38 MAPK activity is stimulated by vascular endothelial growth factor receptor 2 activation and is essential for shear stress‐induced angiogenesis

Gee

Milkiewicz

Haas

2009

Journal Cellular Physiology

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“…Mechanobiology has gained enormous interest in the cardiovascular field, as force-dependent protein activation and gene expression are important regulators of vascular function (Davies et al, 2005;Wasserman and Topper 2004;Resnick et al, 2003). Biomechanical forces that act upon the heart and blood vessels include shear stress and (cyclic) stretch.…”

Section: Introductionmentioning

confidence: 99%

Primary cilia sensitize endothelial cells for fluid shear stress

Hierck

Heiden

Alkemade

et al. 2008

Developmental Dynamics

157

108

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Primary cilia are mechanosensors for fluid shear stress, and are involved in a number of syndromes and congenital anomalies. We identified endothelial cilia in areas of low shear stress in the embryonic heart. The objective of the present study was to demonstrate the role of primary cilia in mechanosensing. Ciliated embryonic endothelial cells were cultured from the heart, and non-ciliated cells from the arteries. Nonciliated cells that were subjected to fluid shear stress showed significantly less induction of the shear marker Krü ppel-Like Factor-2, as compared to ciliated cells. In addition, ciliated cells from which the cilia were chemically removed show a similar decrease in flow response. This shows that primary cilia sensitize endothelial cells for fluid shear stress. In addition, we targeted and stabilized the connection of the cilium to the cytoplasm by treatment with Colchicine and Taxol/Paclitaxel, respectively, and show that microtubular integrity is essential to sense shear stress. Developmental Dynamics 237:725-735, 2008.

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“…In vitro effects of cigarette smoke on vascular endothelial cells include impaired endothelial cell survival [7], induction of apoptosis [8], increased expression of vascular cell adhesion molecule-1 (VCAM-1), enhanced leukocyte adhesion [9], and increased endothelial cell inflammation [10]. Hemodynamic shear stress can inhibit inflammatory gene expression by vascular endothelial cells [11] under physiologic blood flow conditions, and induce endothelial cell activation and apoptosis [12], as well as platelet activation [13] under altered blood flow conditions. Complement activation is an important component of the local and systemic inflammatory response and participates in instructing adaptive immunity.…”

Section: Introductionmentioning

confidence: 99%

Regulated complement deposition on the surface of human endothelial cells: Effect of tobacco smoke and shear stress

Yin

Ghebrehiwet

Weksler

et al. 2008

Thrombosis Research

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Cigarette smoke and hemodynamic stress both contribute to vascular inflammation and associated atherosclerosis. We recently demonstrated direct activation of complement components C4 and C3 on human endothelial cells (EC). The present study was designed to explore complement activation on bone marrow microvascular endothelial cells (BMEC) and human umbilical vein endothelial cells (HUVEC) in response to endothelial cell injury by tobacco smoke extract, shear stress, or other known inflammatory and atherogenic mediators, lipopolysaccharide (LPS) and INF-γ. Following treatment, confluent EC monolayers were exposed to plasma (60 min, 37 °C), and cell surface deposition of stable complement derivatives C4d, iC3b and SC5b-9 was measured in situ using an ELISA approach. Consistent with previous results, moderate levels of C4d, iC3b and SC5b-9 deposition were observed on native EC monolayers exposed to human plasma. Tobacco smoke and shear stress enhanced EC C4d deposition. In contrast, LPS and INF-γ failed to affect EC mediated complement activation, despite evidence of EC activation illustrated by ICAM-1 expression. The combination of tobacco smoke and shear stress nearly doubled EC C4d expression. No increases in iC3b or SC5b-9 were noted, suggesting inhibition of classical and alternative pathway C3 convertase assembly or activity. Indeed, concomitantly increased surface expression of complement regulatory proteins CD35 (CR1) and CD55 was observed following EC exposure to tobacco smoke and shear stress. These results suggest that a balance between complement activation and regulation exists at the EC surface, and may impact vascular injury leading to thrombosis, arteriosclerosis, and atherogenesis.

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Fluid shear stress and the vascular endothelium: for better and for worse

Cited by 495 publications

References 149 publications

p38 MAPK activity is stimulated by vascular endothelial growth factor receptor 2 activation and is essential for shear stress‐induced angiogenesis

p38 MAPK activity is stimulated by vascular endothelial growth factor receptor 2 activation and is essential for shear stress‐induced angiogenesis

Primary cilia sensitize endothelial cells for fluid shear stress

Regulated complement deposition on the surface of human endothelial cells: Effect of tobacco smoke and shear stress

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