Cyclic stretch induces cyclooxygenase-2 gene expression in vascular endothelial cells via activation of nuclear factor kappa-β

Zhao, Haige; Hiroi, Toyoko; Hansen, Baranda S.; Rade, Jeffrey J.

doi:10.1016/j.bbrc.2009.09.028

Cited by 28 publications

(23 citation statements)

References 20 publications

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“…Another NFAT5 target that was identified by our initial microarray approach and confirmed by following expression analyses of hypertension-exposed arteries appears to be Ptgs2 (Cox2). Originally described to be transcriptionally regulated by NFAT5 in renal epithelial cells upon hypertonic stimulation (22), COX2 expression in mechanoactivated cells is thought to be controlled by the transcription factor NF-kB (54). Interestingly, recent reports suggest that NFAT5 is capable of forming an enhanceosome with NF-kB, which is required to recruit p300 (55).…”

Section: Discussionmentioning

confidence: 99%

Genetic ablation of NFAT5/TonEBP in smooth muscle cells impairs flow‐ and pressure‐induced arterial remodeling in mice

et al. 2018

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The arterial wall adapts to alterations in blood flow and pressure by remodeling the cellular and extracellular architecture. Biomechanical stress of vascular smooth muscle cells (VSMCs) in the media is thought to precede this process and promote their activation and subsequent proliferation. However, molecular determinants orchestrating the transcriptional phenotype under these conditions have been insufficiently studied. We identified the transcription factor, nuclear factor of activated T cells 5 (NFAT5; or tonicity enhancer‐binding protein) as a crucial regulatory element of mechanical stress responses of VSMCs. Here, the relevance of NFAT5 for arterial growth and thickening is investigated in mice upon inducible smooth muscle cell (SMC)‐specific genetic ablation of Nfat5. In cultured mouse VSMCs, loss of Nfat5 inhibits the expression of gene sets involved in the control of the cell cycle and the interaction with the extracellular matrix and cytoskeletal dynamics. In vivo, SMC‐specific knockout of Nfat5 did not affect the general vascular architecture and blood pressure levels under baseline conditions. However, proliferation of VSMCs and the thickening of the arterial wall were inhibited during both flow‐induced collateral remodeling and hypertension‐mediated arterial hypertrophy. Whereas originally described as a hypertonicity‐responsive transcription factor, these findings identify NFAT5 as a novel molecular determinant of biomechanically induced phenotype changes of VSMCs and wall stress‐induced arterial remodeling processes.—Arnold, C., Feldner, A., Zappe, M., Komljenovic, D., De La Torre, C., Ruzicka, P., Hecker, M., Neuhofer, W., Korff, T. Genetic ablation of NFAT5/TonEBP in smooth muscle cells impairs flow‐ and pressure‐induced arterial remodeling in mice. FASEB J. 33, 3364–3377 (2019). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 99%

Genetic ablation of NFAT5/TonEBP in smooth muscle cells impairs flow‐ and pressure‐induced arterial remodeling in mice

et al. 2018

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“…IL-6 is also upregulated in mouse artery VSMCs exposed to cyclical stretch for 2 h [76]. NFĸB also plays a role in COX-2 transcription in HUVECs exposed to cyclical stretch [77]. COX-2 and thromboxane synthase enzymes are involved in the stepwise breakdown of arachidonic acid into prostacyclin and thromboxane-A2.…”

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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“…2.5-fold in endothelial cells. 72 Prior studies have also shown that TGF beta-1 (2 ng/mL) can promote COX-2 protein expression in benign kerationocytes. 73 BMP-2 (100 ng/mL) increased expression of COX-2 mRNA in primary osteoblasts rapidly within several hours, and the induction of PGE 2 was 45% higher in the wild type compared with COX-2 knockout cells.…”

mentioning

confidence: 99%

Response of a Preosteoblastic Cell Line to Cyclic Tensile Stress Conditioning and Growth Factors for Bone Tissue Engineering

Chung

Rylander²

2012

Tissue Engineering Part A

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Bone regeneration can be accelerated by utilizing mechanical stress and growth factors (GFs). However, a limited understanding exists regarding the response of preosteoblasts to tensile stress alone or with GFs. We measured cell proliferation and expression of heat-shock proteins (HSPs) and other bone-related proteins by preosteoblasts following cyclic tensile stress (1%-10% magnitude) alone or in combination with bone morphogenetic protein-2 (BMP-2) and transforming growth factor-b1 (TGF-b1). Tensile stress (3%) with GFs induced greater gene upregulation of osteoprotegerin (3.3 relative fold induction [RFI] compared to sham-treated samples), prostaglandin E synthase 2 (2.1 RFI), and vascular endothelial growth factor (VEGF) (11.5 RFI), compared with samples treated with stimuli alone or sham-treated samples. The most significant increases in messenger RNA expression occurred with GF addition to either static-cultured or tensile-loaded (1% elongation) cells for the following genes: HSP47 (RFI = 2.53), cyclooxygenase-2 (RFI = 72.52), bone sialoprotein (RFI = 11.56), and TGF-b1 (RFI = 8.05). Following 5% strain with GFs, VEGF secretion increased 64% (days 3-6) compared with GF alone and cell proliferation increased 23% compared with the sham-treated group. GF addition increased osteocalcin secretion but decreased matrix metalloproteinase-9 significantly (days 3-6). Tensile stress and GFs in combination may enhance bone regeneration by initiating angiogenic and anti-osteoclastic effects and promote cell growth.

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Cyclic stretch induces cyclooxygenase-2 gene expression in vascular endothelial cells via activation of nuclear factor kappa-β

Cited by 28 publications

References 20 publications

Genetic ablation of NFAT5/TonEBP in smooth muscle cells impairs flow‐ and pressure‐induced arterial remodeling in mice

Genetic ablation of NFAT5/TonEBP in smooth muscle cells impairs flow‐ and pressure‐induced arterial remodeling in mice

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

Response of a Preosteoblastic Cell Line to Cyclic Tensile Stress Conditioning and Growth Factors for Bone Tissue Engineering

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