Differential gene responses in endothelial cells exposed to a combination of shear stress and cyclic stretch

Toda, Masahisa; Yamamoto, Kimiko; Shimizu, Nobuyoshi; Obi, Syotaro; Kumagaya, Shinichiro; Igarashi, Takashi; Kamiya, Akira; Ando, Jun

doi:10.1016/j.jbiotec.2007.08.009

Cited by 54 publications

(50 citation statements)

References 26 publications

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“…Exercise-induced increases in blood flow and, thus, shear stress to the artery wall is a likely mechanism by which physical activity exerts an insulin-sensitizing effect on the aorta and a decrease in ET-1 (24,44). This hypothesis is supported by evidence that 1) shear stress reduces expression of ET-1 in cultured endothelial cells (59), 2) removal of WR for 7 days increases expression of ET-1 in the rat iliac artery (41), 3) rat soleus muscle feed arteries, known to be chronically exposed to high levels of blood flow, display greater insulin-stimulated dilation, as a result of reduced ET-1 activation, than gastrocnemius feed arteries, known to be chronically exposed to lower levels of flow (26), and 4) inactive lower limbs of spinal cord injury patients, chronically exposed to low blood flow and shear stress (3), exhibit an enhanced ET-1-mediated basal vascular tone (58).…”

Section: Discussionmentioning

confidence: 89%

Adipose tissue and vascular phenotypic modulation by voluntary physical activity and dietary restriction in obese insulin-resistant OLETF rats

Crissey

Jenkins

Lansford

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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Adipose tissue (AT)-derived cytokines are proposed to contribute to obesity-associated vascular insulin resistance. We tested the hypothesis that voluntary physical activity and diet restriction-induced maintenance of body weight would both result in decreased AT inflammation and concomitant improvements in insulin-stimulated vascular relaxation in the hyperphagic, obese Otsuka Long-Evans Tokushima fatty (OLETF) rat. Rats (aged 12 wk) were randomly assigned to sedentary (SED; n ϭ 10), wheel running (WR; n ϭ 10), or diet restriction (DR; n ϭ 10; fed 70% of SED) for 8 wk. WR and DR rats exhibited markedly lower adiposity (7.1 Ϯ 0.4 and 15.7 Ϯ 1.1% body fat, respectively) relative to SED (27 Ϯ 1.2% body fat), as well as improved blood lipid profiles and systemic markers of insulin resistance. Reduced adiposity in both WR and DR was associated with decreased AT mRNA expression of inflammatory genes (e.g., MCP-1, TNF-␣, and IL-6) and markers of immune cell infiltration (e.g., CD8, CD11c, and F4/80). The extent of these effects were most pronounced in visceral AT compared with subcutaneous and periaortic AT. Markers of inflammation in brown AT were upregulated with WR but not DR. In periaortic AT, WR-and DR-induced reductions in expression and secretion of cytokines were accompanied with a more atheroprotective gene expression profile in the adjacent aortic wall. WR, but not DR, resulted in greater insulin-stimulated relaxation in the aorta; an effect that was, in part, mediated by a decrease in insulin-induced endothelin-1 activation in WR aorta. Collectively, we show in OLETF rats that lower adiposity leads to less AT and aortic inflammation, as well as an exercise-specific improvement in insulin-stimulated vasorelaxation. calorie restriction; exercise; gene expression; inflammation; obesity MORE THAN ONE-THIRD OF AMERICANS are obese (38), and the causes underlying the obesity epidemic appear to be largely related to physical inactivity and overnutrition, a set of behaviors increasingly prevalent in our society (5-7, 11, 57). Cumulative evidence indicates that obesity is an important contributor to the development of whole body insulin resistance, Type 2 diabetes, and cardiovascular disease (21). A critical link between obesity and its associated metabolic and cardiovascular diseases is thought to be chronic low-grade systemic inflammation (21). In this regard, recent studies implicate adipose tissue (AT) as a local and systemic source of inflammatory cytokines that may be involved in the instigation of vascular insulin resistance and atherosclerosis associated with obesity (12, 13, 19, 20, 31, 33-36, 45, 46, 51, 55, 56). Indeed, excessive lipid accumulation and enlargement of adipocytes in obesity are associated with infiltration of immune cells into AT, contributing to AT inflammation and subsequent secretion of proinflammatory cytokines (52). A deeper understanding of the influence of lifestyle modifications on AT inflammation and vascular insulin resistance may lead to more effective strategies aimed at prevent...

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Section: Discussionmentioning

confidence: 89%

Adipose tissue and vascular phenotypic modulation by voluntary physical activity and dietary restriction in obese insulin-resistant OLETF rats

Crissey

Jenkins

Lansford

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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“…This suggests that the ET-1 activity is controlled by the balance between the two forces. The combination of these two mechanical forces acts to neutralise the effect on ET-1 (for expression of stretch-induced genes in inflammation, see table 2) [65,66]. In addition to causing vasoconstriction, stretch-induced ET-1 mRNA from arterial ECs has been reported to affect VSMCs by increasing apoptosis [67].…”

Section: Stretch-regulated Genes Affecting the Inflammatory Response mentioning

confidence: 99%

The Effect of Pressure-Induced Mechanical Stretch on Vascular Wall Differential Gene Expression

et al. 2012

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High blood pressure is responsible for the modulation of blood vessel morphology and function. Arterial hypertension is considered to play a significant role in atherosclerotic ischaemic heart disease, stroke and hypertensive nephropathy, whereas high venous pressure causes varicose vein formation and chronic venous insufficiency and contributes to vein bypass graft failure. Hypertension exerts differing injurious forces on the vessel wall, namely shear stress and circumferential stretch. Morphological and molecular changes in blood vessels ascribed to elevated pressure consist of endothelial damage, neointima formation, activation of inflammatory cascades, hypertrophy, migration and phenotypic changes in vascular smooth muscle cells, as well as extracellular matrix imbalances. Differential expression of genes encoding relevant factors including vascular endothelial growth factor, endothelin-1, interleukin-6, vascular cell adhesion molecule, intercellular adhesion molecule, matrix metalloproteinase-2 and -9 and plasminogen activator inhibitor-1 has been explored using ex vivo cellular or organ stretch models and in vivo experimental animal models. Identification of pertinent genes may unravel new therapeutic strategies to counter the effects of pressure-induced stretch on the vessel wall and hence minimise its notable complications.

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“…In vitro experiments in which cultured ECs have been subjected to controlled levels of shear stress in fluid-dynamically designed flow-loading devices, in particular, have enabled analysis of EC responses to shear stress at cellular and molecular levels. [4][5][6][7] In this section, we describe the effects of shear stress on EC morphology, function, and gene expression, and on the differentiation of immature cells, such as endothelial progenitor cells (EPCs) and embryonic stem (ES) cells, into ECs. …”

mentioning

confidence: 99%

Vascular Mechanobiology Endothelial Cell Responses to Fluid Shear Stress

Ando

Yamamoto

2009

Circ J

Self Cite

315

138

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lood vessels are not just tubes through which the blood passes, but are active organs with a variety of functions that maintain the homeostasis of the circulatory system. It is a well-established fact that vascular functions are controlled by biochemical mediators, including hormones, cytokines, and neurotransmitters. However, it has recently become apparent that the biomechanical forces generated by blood flow and blood pressure regulate vascular functions. Flowing blood constantly exerts a frictional force, shear stress, on the endothelial cells (ECs) lining blood vessel walls, and the ECs respond to shear stress by changing their morphology, function, and gene expression. EC responses to shear stress are thought to play a critical role in blood-flow-dependent phenomena, including angiogenesis, 1 vascular remodeling, 2 and atherosclerosis. 3 The fact that ECs respond to shear stress indicates that they have the ability to sense shear stress as a signal and transmit it into the interior of the cell. Numerous studies have been devoted to clarifying the mechanisms of shear stress mechanotransduction, and they have demonstrated that multiple signal transduction pathways are activated by shear stress through a variety of membrane molecules and cellular microdomains, including ion channels, G protein, tyrosine kinase receptors, adhesive proteins, caveolae, the cytoskeleton, the glycocalyx, and primary cilia. The mechanisms of shear stress mechanotransduction, however, are not yet fully understood. We review the literature on EC responses to shear stress and the role of their responses in the regulation of the circulatory system, and address the issues of shear stress sensing and signaling mechanisms. EC Responses to Shear StressA considerable amount of information on EC responses to shear stress has accumulated as a result of various in vivo, ex vivo, and in vitro experiments. In vitro experiments in which cultured ECs have been subjected to controlled levels of shear stress in fluid-dynamically designed flow-loading devices, in particular, have enabled analysis of EC responses to shear stress at cellular and molecular levels. [4][5][6][7] In this section, we describe the effects of shear stress on EC morphology, function, and gene expression, and on the differentiation of immature cells, such as endothelial progenitor cells (EPCs) and embryonic stem (ES) cells, into ECs. MorphologyWhen examined in vivo, ECs lining segments of blood vessels in which blood flow is rapid and unidirectional are spindle-shaped and aligned with their long axis parallel to the direction of blood flow, whereas ECs lining segments in which blood flow is turbulent or stagnant are much rounder in shape and do not have a uniform orientation. 8,9 Because of these findings, shear stress is thought to determine the shape and orientation of ECs. When cultured ECs have been J 2009; 73: 1983 -1992)

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Differential gene responses in endothelial cells exposed to a combination of shear stress and cyclic stretch

Cited by 54 publications

References 26 publications

Adipose tissue and vascular phenotypic modulation by voluntary physical activity and dietary restriction in obese insulin-resistant OLETF rats

Adipose tissue and vascular phenotypic modulation by voluntary physical activity and dietary restriction in obese insulin-resistant OLETF rats

The Effect of Pressure-Induced Mechanical Stretch on Vascular Wall Differential Gene Expression

Vascular Mechanobiology Endothelial Cell Responses to Fluid Shear Stress

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