TLR4 mice
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ABSTRACT:
PROVIDER: PRJEB64887 | ENA |
REPOSITORIES: ENA
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Project description:TLR4 knockout mice partially protected from arterial stiffness.
| PRJEB61188 | ENA
Project description:The mechanisms of arterial stiffness (independent cardiovascular risk factor) are not well understood. Here, we investigated the role of Fibulin V in arterial stiffness and remodeling in response to disturbed blood flow.
2024-10-01 | GSE222583 | GEO
Project description:B-cell leukemia 11b (BCL11B) is a transcription factor known as an essential regulator of T lymphocytes and neuronal development during embryogenesis. A genome-wide association study (GWAS) showed that a gene desert region downstream of BCL11B, known to function as a BCL11B enhancer, harbors single nucleotide polymorphisms (SNPs) associated with increased arterial stiffness. However, a role for BCL11B in the adult cardiovascular system is unknown. Based on these human findings, we sought to examine the relation between BCL11B and arterial function. Here we report that BCL11B is expressed in the vascular smooth muscle (VSM) where it regulates vascular stiffness. RNA sequencing of aortas from WT and Bcl11b null mice (BSMKO) identified the cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) as the most significant differentially regulated signaling pathway in BSMKO compared to WT mice. BSMKO aortas showed decreased levels of PKG1, increased levels of Ca++-calmodulin-dependent serine/threonine phosphatase calcineurin (PP2B) and their common phosphorylation target, vasodilator-stimulated phosphoprotein (pVASPS239), a regulator of cytoskeletal actin rearrangements. Decreased pVASPS239 in BSMKO aortas was associated with increased actin polymerization (F/G actin ratio). Functionally, aortic force, stress, wall tension and stiffness, measured ex vivo in organ baths, were increased in BSMKO aortas, and BSMKO mice had increased pulse wave velocity, the in vivo index of arterial stiffness. Despite having no effect on blood pressure or microalbuminuria, increased arterial stiffness in BSMKO mice was associated with increased incidence of cerebral microbleeds compared to age-matched WT littermates. In conclusion, we have identified VSM BCL11B as a crucial regulator of aortic smooth muscle function and a potential therapeutic target for vascular stiffness.
2021-12-01 | GSE163551 | GEO
Project description:BACKGROUND: Previous genomic studies with human tissues have compared differential gene expression between 2 conditions (ie, normal versus diseased) to identify altered gene expression in a binary manner; however, a potentially more informative approach is to correlate the levels of gene expression with quantitative physiological parameters. METHODS AND RESULTS: In this study, we have used this approach to examine genes whose expression correlates with arterial stiffness in human aortic specimens. Our data identify 2 distinct groups of genes, those associated with cell signaling and those associated with the mechanical regulation of vascular structure (cytoskeletal-cell membrane-extracellular matrix). Although previous studies have concentrated on the contribution of the latter group toward arterial stiffness, our data suggest that changes in expression of signaling molecules play an equally important role. Alterations in the profiles of signaling molecules could be involved in the regulation of cell cytoskeletal organization, cell-matrix interactions, or the contractile state of the cell. CONCLUSIONS: Although the influence of smooth muscle contraction/relaxation on arterial stiffness could be controversial, our provocative data would suggest that further studies on this subject are indicated.<br><br>Note that files GSM6179.txt and GSM6182.txt as imported from GEO are identical.
2007-12-13 | E-GEOD-420 | biostudies-arrayexpress
Project description:We are investigating of role of RhoBTB1 in vascular smooth muscle cells. Restoring RhoBTB1 expression in mouse aorta reversed the established arterial stiffness but not hypertension caused by angiotensin II (Ang-II). To investigate the underlying mechanism by which RhoBTB1 reversed arterial stiffness, we performed bulk RNA-sequencing using aorta from four groups: control /RhoBTB1 transgenic mice treated with/without Ang-II.
2022-04-08 | GSE189003 | GEO
Project description:A number of studies have proposed that excess food intake, particularly of high fat diets arise due dysregulation of homeostatic mechanisms regulating neuroendocrine control of appetite and energy balance. Current dogma suggests high fat diets invoke hypothalamic inflammation which reduces hypothalamic sensitivity to metabolic and hormonal cues of conveying peripheral status of energy balance, such as leptin and insulin. A hypothesis for the mechanism leading to hypothalamic inflammation is based on high fat diet mediated changes in gut microbiota which are then proposed to increase circulating levels of lipopolysaccharide (LPS). This in turn activates a hypothalamic inflammatory response via the toll-like receptor (TLR4) and CD14. The aim of this study was to determine hypothalamic gene expression in response to long term feeding of a high fat diet, taking into account the importance of using a control diet with a similar composition and balanced for sucrose content.
2018-10-23 | E-MTAB-6929 | biostudies-arrayexpress
Project description:Arterial stiffness is a prevalent, independent cardiovascular risk factor, but the underlying mechanisms are not well understood. Wall shear stress and shear-sensitive genes may promote arterial stiffening through clinically important signaling pathways. Our goal was to identify how disturbed blood flow leads to arterial stiffness using the mouse partial carotid ligation model. Here we used our in vivo partial carotid ligation model to induce d-flow in the LCA while the contralateral RCA continues to experience stable laminar flow using the C57BL/6x129SvEv mice, TSP-1 knockout (KO), and C57Bl/6J mice. We compared these to aged (80 week) mice which had increased arterial stiffness due to aging. Changes in gene expression were identified using microarrays that were performed on the endothelial-enriched RNA isolated from the carotids exposed to stable flow (RCA) and compared to disturbed flow (LCA). Arterial stiffness was determined ex vivo by biaxial mechanical testing and in vivo by ultrasound techniques. Myointimal hyperplasia and immunohistochemistry were performed in sectioned carotid arteries. In vitro testing of signaling pathways utilized oscillatory and laminar wall shear stress. Human arteries were tested ex vivo to validate critical results found in the animal model.
2017-09-01 | GSE87199 | GEO
Project description:Sirtuin1 (Sirt1) in skeletal muscle (SK) and fat protects against metabolic damage by stimulating insulin sensitivity. Here we report that mice with selective deletion of endothelial Sirt1 (E-Sirt1-KO) paradoxically exhibit heightened whole-body insulin sensitivity. Akt phosphorylation, glucose uptake, and glycolysis are boosted in SK and brown adipose tissue (BAT) of E-Sirt1-KO mice. E-Sirt1-KO mice have higher energy expenditure and are partially protected from high-fat diet-induced insulin resistance. Enhanced insulin sensitivity and peripheral tissue Akt phosphorylation in E-Sirt1-KO mice is transferrable to wild-type mice via the systemic circulation after surgical parabiosis. Silencing of Sirt1 in endothelial cells upregulates transcription of the F-actin-binding protein thymosin beta-4 (Tβ4), whose secretion activates Akt in skeletal myotubes. Sirt1 downregulation stimulates endothelial Tβ4 transcription through inhibition of autophagy and upregulation of nuclear factor-kappa B signaling. Thus, unlike Sirt1 in skeletal muscle and fat, endothelial Sirt1 curtails whole-body insulin sensitivity by inhibiting expression of secreted Tβ4.
2023-08-07 | PXD030565 | Pride
Project description:Gut microbiota linked to arterial stiffness
| PRJEB49672 | ENA
Project description:Plasmacytoid dendritic cells (pDCs) are a rare type of dendritic cells that exist antiviral functions in response to toll-like receptors (TLRs). We here report TLR4 activated pDCs similar to TLR7/8 stimulation. Despite the high resemblance, we found the unique genes that were activated by TLR4 activation.
2023-07-31 | GSE236923 | GEO