Transcriptional profiling of murine porcine-pancreatic elastase-induced abdominal aortic aneurysm at day 7, with parallel miRNA profiling and miR-24 in vivo modulation.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE51229 | GEO | 2014/08/31
SECONDARY ACCESSION(S): PRJNA221774
REPOSITORIES: GEO
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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-08-31 | E-GEOD-51229 | biostudies-arrayexpress
Project description:We sought to identify differentially regulated microRNAs in infrarenal mouse aortic tissue after AAA-induction with PPE, compared with sham-operated mice. This treatment leads to rapid development of infrarenal aortic aneurysms with significant diameter differences observed by Day 7. We found 41 miRNAs were up-regulated with aneurysm and 37 down-regulated at p<0.05, which were also altered by >1.5-fold.
2014-08-31 | GSE51226 | GEO
Project description:We sought to identify differentially regulated microRNAs in infrarenal mouse aortic tissue after AAA-induction with PPE, compared with sham-operated mice. This treatment leads to rapid development of infrarenal aortic aneurysms with significant diameter differences observed by Day 7. We found 41 miRNAs were up-regulated with aneurysm and 37 down-regulated at p<0.05, which were also altered by >1.5-fold. Utilizing the PPE infusion model, we induced AAA in Male 10-week-old C57/Bl6 mice, 7 days after AAA-induction with PPE. One array per mouse, 5 mice per group, two groups (PPE and sham).
2014-08-31 | E-GEOD-51226 | biostudies-arrayexpress
Project description:Transcriptional profiling of infrarenal aortic tissue from Male 10-week-old C57BL/6J mice after AAA-induction with porcine pancreatic elastase, compared with sham-operated saline-injected mice. One day after AAA-induction, the mice were injected intraperitoneally with either lentiviral packaged miR-24 antagomir (anti-miR-24) or miR-24 mimic (pre-miR-24), or a scrambled microRNA control (scr-miR). Aortic samples were obtained 7 days after operation. The goal was to examine gene expression in developing AAA in this model, and to compare the effects of scr-miR, anti-miR-24 and pre-miR-24. Four condition experiment, one infrarenal aorta per array. Sham vs. scr-miR-PPE vs. anti-miR-24-PPE vs. pre-miR-24-PPE, all harvested at Day 7 post-operatively. After QC, the final analysis group (uploaded here) consisted of 18 arrays: Sham-Saline-treated (4 arrays), scr-miR-PPE-treated (5 arrays); pre-miR-24-PPE-treated (3 arrays); and anti-miR-24-PPE-treated (6 arrays).
2014-08-31 | E-GEOD-51228 | biostudies-arrayexpress
Project description:Transcriptional profiling of infrarenal aortic tissue from Male 10-week-old C57BL/6J mice after AAA-induction with porcine pancreatic elastase, compared with sham-operated saline-injected mice. One day after AAA-induction, the mice were injected intraperitoneally with either lentiviral packaged miR-24 antagomir (anti-miR-24) or miR-24 mimic (pre-miR-24), or a scrambled microRNA control (scr-miR). Aortic samples were obtained 7 days after operation. The goal was to examine gene expression in developing AAA in this model, and to compare the effects of scr-miR, anti-miR-24 and pre-miR-24.
2014-08-31 | GSE51228 | GEO
Project description:Macrophages play an important role in the inflammatory process that contributes to the development of abdominal aortic aneurysm (AAA). Studies of human and mouse AAA tissue reveal expanded populations of macrophages producing an abundance of pro-inflammatory cytokines, including TNF-α, IL-12p40 and high level of metalloprotease 9 (MMP-9) at the late stages of disease. Herein, we show that blockade of IL-12p40 in the early phase of aneurysm development suppresses macrophage expansion, inflammatory cytokine and MMP-9 production and mitigates AAA development. Since IL-12 and IL-23 are related cytokines that share the common p40 subunit, we also evaluate the effect of direct IL-23 blockade on the development of AAA. Specific IL-23p19 blockade prevents AAA progression with the same efficiency as IL-12p40 antagonism, suggesting that the efficacy of anti-IL-12p40 treatment may reflect IL-23 blockade. IL-12p40 and IL-23p19 are also abundantly expressed in human AAA tissue. Our findings have potential translational value since IL-12p40 and IL-23p19 antagonists already exist as FDA-approved therapeutics for various chronic inflammatory conditions.
| S-EPMC6639297 | biostudies-literature
Project description:Murine models have proved instrumental in studying various aspects of abdominal aortic aneurysm (AAA), from identification of underlying pathophysiologic changes to the development of novel therapeutic strategies. In the current study, we describe a new model in which an elastase-treated donor aorta is transplanted to a recipient mouse and allowed to progress to aneurysm. We hypothesized that by transplanting an elastase-treated abdominal aorta of one genotype to a recipient mouse of a different genotype, one can differentiate pathophysiologic factors that are intrinsic to the aortic wall from those stemming from circulation and other organs.Elastase-treated aorta was transplanted to the infrarenal abdominal aorta of recipient mice by end-to-side microsurgical anastomosis. Heat-inactivated elastase-treated aorta was used as a control. Syngeneic transplants were performed with use of 12-week-old C57BL/6 littermates. Transplant grafts were harvested from recipient mice on day 7 or day 14 after surgery. The aneurysm outcome was measured by aortic expansion, elastin degradation, proinflammatory cytokine expression, and inflammatory cell infiltration and compared with that produced with the established, conventional elastase infusion model.The surgical technique success rate was 75.6%, and the 14-day survival rate was 51.1%. By day 14 after surgery, all of the elastase-treated transplanted abdominal aortas had dilated and progressed to AAAs, defined as 100% or more increase in the maximal external diameter compared with that measured before elastase perfusion, whereas none of the transplanted aortas pretreated with inactive elastase became aneurysmal (percentage increase in maximum aortic diameter: 159.36% ± 23.27%, transplanted elastase, vs 41.46% ± 9.34%, transplanted inactive elastase). Aneurysm parameters, including elastin degradation and infiltration of macrophages and T lymphocytes, were found to be identical to those observed in the conventional elastase model. Quantitative polymerase chain reaction analysis revealed similarly increased levels of proinflammatory cytokines (relative changes of mRNA in the conventional elastase model vs transplant model: tumor necrosis factor ?, 1.71 ± 0.27 vs 2.93 ± 0.86; monocyte chemoattractant protein 1, 2.36 ± 0.58 vs 2.87 ± 0.51; chemokine (C-C motif) ligand 5, 3.37 ± 0.92 vs 3.46 ± 0.83; and interferon ?, 3.09 ± 0.83 vs 5.30 ± 1.69). Using green fluorescent protein transgenic mice as donors or recipients, we demonstrated that a small quantity of mononuclear leukocytes in the transplant grafts bared the genotype of the donors.Transplanted elastase-treated abdominal aorta could develop to aneurysm in recipient mice. This AAA transplant model can be used to examine how the microenvironment of a transplanted aneurysmal aorta may be altered by the contributions of the "global" environment of the recipient.
| S-EPMC4277509 | biostudies-literature
Project description:Demonstrate that periadventitial delivery of adipose-derived mesenchymal stem cells (ADMSCs) slows aneurysm progression in an established murine elastase-perfusion model of abdominal aortic aneurysm (AAA).AAAs were induced in C57BL/6 mice using porcine elastase. During elastase perfusion, a delivery device consisting of a subcutaneous port, tubing and porous scaffold was implanted. Five days after elastase perfusion, 100,000 ADMSCs were delivered through the port to the aorta. After sacrifice at day 14, analyzed metrics included aortic diameter and structure of aortic elastin.ADMSC treated aneurysms had a smaller diameter and less fragmented elastin versus saline controls.Periadventitial stem cell delivery prevented the expansion of an established aneurysm between days 5 and 14 after elastase perfusion.
| S-EPMC4283481 | biostudies-literature
Project description:Identification and treatment of abdominal aortic aneurysm (AAA) remain among the most prominent challenges in vascular medicine. MicroRNAs (miRNAs) are crucial regulators of cardiovascular pathology and represent intriguing targets to limit AAA expansion. Here we show, by using two established murine models of AAA disease along with human aortic tissue and plasma analysis, that miR-24 is a key regulator of vascular inflammation and AAA pathology. In vivo and in vitro studies reveal chitinase 3-like 1 (Chi3l1) to be a major target and effector under the control of miR-24, regulating cytokine synthesis in macrophages as well as their survival, promoting aortic smooth muscle cell migration and cytokine production, and stimulating adhesion molecule expression in vascular endothelial cells. We further show that modulation of miR-24 alters AAA progression in animal models, and that miR-24 and CHI3L1 represent novel plasma biomarkers of AAA disease progression in humans.
| S-EPMC4217126 | biostudies-literature
Project description:We previously established that neutrophils play a critical role in the development of experimental abdominal aortic aneurysm (AAA). The signal that initiates the influx of neutrophils to the aortic wall, however, remains unknown. In this study, we tested the hypothesis that complement participates in the development of AAA by providing the necessary chemotactic signal that recruits neutrophils to the aortic wall.Using an elastase-induced model of AAA, we showed that pretreatment of C57BL/6 mice with cobra venom factor, which depleted serum of complement activity, protected mice from AAA development. Whereas control mice exhibited a mean aortic diameter of 156+/-2% on day 14 after elastase perfusion, mice treated with cobra venom factor exhibited a mean aortic diameter of 90+/-4% (P<0.001). Examination of mice deficient in factor B further indicated that the alternative pathway of complement played a major role in this process (mean aortic diameter of 105+/-4% in factor B-deficient mice, P<0.001 compared with controls). Activation of the alternative pathway led to generation of the anaphylatoxins C3a and C5a, which recruited neutrophils to the aortic wall. Moreover, antagonism of both C3a and C5a activity was required to block AAA, which suggests that each can independently promote the aneurysmal phenotype. In addition, we demonstrated that complement alternative-pathway involvement was not restricted to this experimental model but was also evident in human AAAs.The identification of involvement of the complement system in the pathophysiology of AAA provides a new target for therapeutic intervention in this common disease.
| S-EPMC2758616 | biostudies-literature