Sustained down-regulation of alphaSmooth muscle actin expression in aortas induced by angiotensin II: a new model of vascular memory to hypertension
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE175588 | GEO | 2022/01/14
REPOSITORIES: GEO
Similar Datasets
Project description:Objective-Aortic pathologies exhibit sexual dimorphism, with aneurysms in the ascending, thoracic and abdominal aorta (AAA) exhibiting higher prevalence in males. Despite lower incidence of aortic vascular disease in women, aneurysms progress rapidly. Mechanisms for these sex differences are unclear. We defined the role of sex chromosome complement and testosterone in regional development and progression of angiotensin II (AngII)-induced vascular pathologies. Approach and Results-We used transgenic male mice expressing Sry on an autosome to create low density lipoprotein receptor (Ldlr) deficient male mice with an XY or XX sex chromosome complement. Subjects were then sham operated or orcheictomized. Transcriptional profiling on abdominal aortas from XY or XX males demonstrated1746 genes influenced by sex chromosomes, sex hormones, or an interaction. A second cohort of animals was then infused with AngII for 28 days. Diffuse aortic aneurysm pathology developed in XY AngII-infused males, while XX males developed discrete AAAs. Castration reduced all AngII-induced aortic pathologies in XY and XX males. Thoracic aortas from AngII-infused XY males, but not XX males exhibited adventitial thickening. We infused male XY and XX mice with saline or AngII and quantified mRNA abundance of key genes in thoracic versus abdominal aortas. Regional differences in mRNA abundance existed before AngII infusions, which were differentially influenced by AngII between genotypes. Prolonged AngII infusions resulted in AAA aortic wall thickening in XY males with diffuse aortic pathology, while XX males had dilated focal AAAs. Conclusions-An XY sex chromosome complement mediates diffuse aortic pathology, while an XX sex chromosome complement contributes to discrete AngII-induced AAAs.
2018-07-22 | GSE102143 | GEO
Project description:Endothelial-enriched total RNAs were obtained from the suprarenal region of the abdominal aorta which is the murine AAA prone area in AngII-infused C57BL/6 mice. At 12 or 36h post-AngII pump implantation, endothelial-enriched RNAs from four abdominal aortas were pooled to obtain ~30 ng total RNA as one array sample, performed in triplicates. All RNA samples used for miRNA microarray study passed the initial quality control test and each sample was linearly amplified.
2014-07-01 | E-GEOD-54943 | biostudies-arrayexpress
Project description:The goals of this study is to identify the differential expressed genes in abdominal aorta of C57BL/6 mice with or without Angiotensin II (AngII) treatment, and compare the differential expressed genes in the abdominal aorta of Ang II infused C57BL/6 mice after Ethoxysanguinarine (ETH), Baicalin (BAI), Gastrodin (GAS) or valsartan (VAL) treatment. Briefly, the mice (n=30) were randomly divided into 6 groups: control, AngII, AngII + ETH, AngII + BAI, AngII + GAS and AngII + VAL groups (n=5 for each group). Mice in Control and AngII groups were infused with saline and 500 ng/kg/min of AngII respectively, and orally administrated with saline; the mice in AngII + ETH, AngII + BAI and AngII + GAS groups were infused with AngII (500 ng/kg/min) and orally administrated with 5 mg/kg /day of ETH, BAI or GAS daily for total 4 weeks. The mice in AngII + VAL group were infused with AngII (500 ng/kg/min) and orally administrated with 10.4mg/kg /day of VAL. Then the abdominal aortas were used to identify differentially expressed genes among different groups.
2021-05-14 | GSE174386 | GEO
Project description:Objective: Turner Syndrome women (monosomy X) have high risk of aortopathies consistent with a role for sex chromosomes in disease development. We demonstrated that sex chromosomes influence regional development of angiotensin II (AngII)-induced aortopathies in mice. In this study, we determined if the number of X chromosomes regulates regional development of AngII-induced aortopathies. Approach and Results: We used females with varying numbers of X chromosomes (XXF or XOF) on an C57BL/6J (ascending aortopathies) or Ldlr-/- background (descending and abdominal aortopathies) compared to XY males (XYM). To induce aortopathies, mice were infused with AngII. XOF (C57BL/6J) exhibited larger percent increases in ascending aortic lumen diameters than AngII-infused XXF or XYM. AngII-infused XOF (Ldlr-/-) exhibited similar incidences of thoracic (XOF, 50%; XYM, 71%) and abdominal aortopathies (XOF, 83%; XYM, 71%) as XYM, which were greater than XXF (XXF, 0%). Abdominal aortic lumen diameters and maximal external diameters were similar between XOF and XYM but greater than XXF, and these effects persisted with extended AngII infusions. Larger aortic lumen diameters, abdominal aortopathy incidence (XXF, 20%; XOF, 75%), and maximal aneurysm diameters (XXF, 1.02 ± 0.17; XOF, 1.96 ± 0.32 mm; P=0.027) persisted in ovariectomized AngII-infused XOF mice. Data from RNA seq demonstrated that X chromosome genes that escape X-inactivation (histone lysine demethylases Kdm5c and Kdm6a), exhibited lower mRNA abundance in aortas of XOF than XXF (P=0.033 and 0.024 respectively). Conversely, DNA methylation was higher in aortas of XOF than XXF (P=0.038). Conclusion: The absence of a second X chromosome promotes diffuse AngII-induced aortopathies in females.
2021-06-27 | GSE154036 | GEO
Project description:Objective - Thoracic aortic aneurysm (TAA), a degenerative disease of the aortic wall, is accompanied by changes in the structure and composition of the aortic extracellular matrix (ECM). The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family has recently been implicated in TAA formation. This study aimed to investigate the contribution of ADAMTS-5 to TAA development. Approach and Results - A model of aortic dilatation by angiotensin II (AngII) infusion was adopted in mice lacking the catalytic domain of ADAMTS-5 (Adamts5Δcat). Adamts5Δcat mice showed an attenuated rise in blood pressure whilst displaying increased dilatation of the ascending aorta. Interestingly, a comparison of the aortic ECM from AngII-treated wildtype and Adamts5Δcat mice revealed versican as the most up-regulated ECM protein in Adamts5Δcat mice. This was accompanied by a marked reduction of ADAMTS-specific versican cleavage products (versikine) and a decrease of low-density lipoprotein-related protein 1 (LRP1). Silencing LRP1 expression in human aortic smooth muscle cells reduced the expression of ADAMTS5, attenuated the generation of versikine but increased soluble ADAMTS-1. A similar increase in ADAMTS-1 was observed in aortas of AngII-treated Adamts5Δcat mice, but was not sufficient to maintain versican processing and prevent aortic dilatation. Conclusions - Our results support the emerging role of ADAMTS proteases in TAA. ADAMTS-5 rather than ADAMTS-1 is the key protease for versican regulation in murine aortas. Further studies are needed to define the ECM substrates of the different ADAMTS proteases and their contribution to TAA formation.
2018-05-08 | PXD009410 | Pride
Project description:We have employed whole genome microarray expression profiling as a platform to identify AngII -regulated genes sensitive to CsA. VSMC were treated with AngII with or without CsA ( as an inhibitor of the CN/NFAT pathway). 4 independent VSMC cultures (4 replicates) from aortas of C57BL/6 mice were used for each condition (1uM AngII or 1uM AngII+200ng/ml CsA).
2011-08-10 | E-GEOD-31321 | biostudies-arrayexpress
Project description:The goals of this study is to compare the differently expressed genes in renal tissue of C57BL/6 WT mice with or without Angiotensin II (AngII) treatment as well as differently expressed genes in the renal tissue of WT mice with AngII treatment with or without Quercetin (Que) treatment. The mice (n=18) were randomly divided into 3 groups: control, AngII,AngII+ Que (n=6 for each group). Mice in Control and AngII groups were infused with saline or 500 ng/kg/min of AngII respectively, and intragastrically with double distilled water (dd H2O); while mice in AngII + Que groups were infused with AngII (500 ng/kg/min) and intragastrically with 5mg/kg/D of Que for 4 weeks. Then the renal tissue were used to identify differentially expressed genes among different groups.
2022-07-15 | GSE207102 | GEO
Project description:Transcriptional profiling of mouse aortas comparing control wild-type animals with aortas from three different Plk1(+/-) mice. Goal was to determine the effects of Plk1 haploinsufficiency in aorta expression profiles.
2017-07-01 | GSE85199 | GEO
Project description:THP-1 cells were differentiated to macrophages with the phorbol 12-myristate 13-acetate (PMA) for a total time of 28 hours. To understand the effects of Angiotensin II (AngII) and of AngII in the presence of the thiazolidinedione pioglitazone (Pio), after 4 hours of PMA-induced differentiation of THP-1 cells (when cells became adherent), the PMA-containing medium was supplemented with AngII (1mg/ml), AngII (1 mg/ml) with Pio (1 uM), or no supplement for another 24 hours. At this time point the cells were harvested, RNA was extracted and used for a microarray-based gene profiling analysis of THP-1 cells, under the three conditions: PMA, AngII and AngII with Pio.
2014-06-01 | E-MTAB-2320 | biostudies-arrayexpress
Project description:The goals of this study is to compare the differently expressed genes in abdominal aorta of C57BL/6 WT mice with or without Angiotensin II (AngII) treatment as well as differently expressed genes in the abdominal aorta of WT mice with AngII treatment with or without Qingda granules (QDG) treatment. The mice (n=15) were randomly divided into 3 groups:control, AngII and QDG treated (n=5 for each group). Mice in Control and AngII groups were infused with saline or 500 ng/kg/min of AngII respectively, and orally administrated with saline; while mice in AngII + QDG group were infused with AngII (500 ng/kg/min) and orally administrated with 1.145 g/kg /day of QDG for 2 weeks. Then the abdominal aorta were used to identify differentially expressed genes among different groups.
2021-01-28 | GSE165601 | GEO