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ABSTRACT:
PROVIDER: PRJEB95754 | ENA |
REPOSITORIES: ENA
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Project description:Fasting Reduces Arterial Stiffness in Obese Mice
| PRJEB94036 | ENA
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:The RhoBTB1-Cullin3 (CUL3) pathway in smooth muscle cells (SMCs) controls the ubiquitination of target proteins and through this blood pressure (BP) and arterial stiffness. We performed APEX2 proximity labelling coupled with mass spectrometry to identify RhoBTB1 interacting partners in A7R5 SMCs. We identified 59 proteins which bound to the C-terminal half of RhoBTB1, the region identified as essential for its adapter function to deliver substrates to CUL3. We examined one of these proteins in detail - RbFox2. Co-immunoprecipitation validated the interaction of RbFox2 with RhoBTB1. Expression of RbFox2 was elevated in response to inhibition of the ubiquitination-proteasomal pathway, CUL3-deficiency, and RhoBTB1 inhibition by either siRNA or angiotensin II (ANG). RbFox2 was ubiquitinated in a RhoBTB1- and CUL3-dependent manner suggesting it is regulated through the RhoBTB1-CUL3-dependent ubiquitin-proteasome pathway. Inhibition of RbFox2 impaired the actin cytoskeleton in A7R5 cells and in primary SMC from RbFox2Flox mice and decreased the levels of globular and filamentous actin. ANG increased BP and arterial stiffness of RbFox2Flox mice, but the progression of arterial stiffness was halted after SMC-specific RbFox2 deletion despite a continued rise in BP. We conclude that RhoBTB1 and its target RbFox2 is an important regulator of arterial stiffness through its actions to regulate the cytoskeleton.
2026-04-06 | PXD067797 | Pride
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: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:The RhoBTB1-Cullin3 (CUL3) pathway in smooth muscle cells (SMCs) controls the ubiquitination of target proteins and through this blood pressure (BP) and arterial stiffness. We performed proximity labelling coupled with mass spectrometry to identify RhoBTB1 interacting partners in A7R5 SMCs. We identified 59 proteins which bound to the C-terminal half of RhoBTB1, the region identified as essential for its adapter function to deliver substrates to CUL3. We examined one of these proteins in detail - RbFox2. Co-immunoprecipitation validated the interaction of RbFox2 with RhoBTB1. Expression of RbFox2 was elevated in response to inhibition of the ubiquitination-proteasomal pathway, CUL3-deficiency, and RhoBTB1 inhibition by either siRNA or angiotensin II (ANG). RbFox2 was ubiquitinated in a RhoBTB1- and CUL3-dependent manner suggesting it is regulated through the RhoBTB1-CUL3-dependent ubiquitin-proteasome pathway. Inhibition of RbFox2 impaired the actin cytoskeleton in A7R5 cells and in primary SMC from RbFox2Flox mice and decreased the levels of globular and filamentous actin. ANG increased BP and arterial stiffness of RbFox2Flox mice, but the progression of arterial stiffness was halted after SMC-specific RbFox2 deletion despite a continued rise in BP. We conclude that RhoBTB1 and its target RbFox2 is an important regulator of arterial stiffness through its actions to regulate the cytoskeleton.
2026-03-24 | GSE305901 | GEO
Project description:Nitric oxide is the smallest gaseous signaling molecule responsible for maintaining homeostasis in a myriad of tissues and molecular pathways in neurological and cardiovascular pathologies. In recent years, there has been increasing interest in the potential interaction between arterial stiffness (AS), an independent cardiovascular risk factor, and neurodegenerative syndromes given increasingly epidemiological study reports. For this reason, we previously sought to investigate the mechanistic convergence between AS and neurodegeneration via the progressive non-selective inhibition of all nitric oxide synthase (NOS) isoforms with N(G)-nitro-L-arginine methyl ester (L-NAME) in C57BL/6 mice. Our results showed progressively increased arterial stiffness in vivo and impaired visuospatial learning and memory in L-NAME treated C57BL/6 mice. In this study, we sought to further investigate the progressive molecular signatures in hippocampal tissue via LC-MS/MS proteomic analysis
2022-08-12 | PXD033646 | Pride
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