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Involvement of B cells, immunoglobulins, and Syk in the pathogenesis of abdominal aortic aneurysm

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE109640 | GEO | 2018/04/25

REPOSITORIES: GEO

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Involvement of B Cells, Immunoglobulins, and Syk in the Pathogenesis of Abdominal Aortic Aneurysm.

Project description:BACKGROUND:Abdominal aortic aneurysm (AAA) is a potentially life-threatening disease that is common in older individuals. Currently, therapeutic options are limited to surgical interventions. Although it has long been known that AAA tissue is enriched in B cells and immunoglobulins, their involvement in AAA pathogenesis remains controversial. METHODS AND RESULTS:We investigated the role of B cells and immunoglobulins in a murine model of AAA, induced with a periaortic application of CaCl2, and in human AAA. Both human and mouse AAA tissue showed B-cell infiltration. Mouse AAA tissue showed deposition of IgG and activation of Syk, a key molecule in B-cell activation and immunoglobulin function, which were localized to infiltrating cells including B cells and macrophages. B-cell-deficient muMT mice showed suppression of AAA development that was associated with reduced activation of Syk and less expression of matrix metalloproteinase-9. Administration of exogenous immunoglobulins restored the blunted Syk activation and AAA development in muMT mice. Additionally, exogenous immunoglobulins induced interleukin-6 and metalloproteinase-9 secretions in human AAA tissue cultures. Furthermore, administration of R788, a specific Syk inhibitor, suppressed AAA expansion, reduced inflammatory response, and reduced immunoglobulin deposition in AAA tissue. CONCLUSIONS:From these results, we concluded that B cells and immunoglobulins participated in AAA pathogenesis by promoting inflammatory and tissue-destructive activities. Finally, we identified Syk as a potential therapeutic target.

| S-EPMC5907549 | biostudies-literature

Involvement of B cells, immunoglobulins, and Syk in the pathogenesis of abdominal aortic aneurysm I

Project description:Background—Abdominal aortic aneurysm (AAA) is a potentially life-threatening disease that is common in older individuals. Currently, therapeutic options are limited to surgical interventions. Although it has long been known that AAA tissue is enriched in B cells and immunoglobulins, their involvement in AAA pathogenesis remains controversial. Methods and Results— We investigated the role of B cells and immunoglobulins in a murine model of AAA, induced with a periaortic application of CaCl2, and in human AAA. Both human and mouse AAA tissue showed B cell infiltration. Mouse AAA tissue showed deposition of IgG and activation of Syk, a key molecule in B cell activation and immunoglobulin function, which were localized to infiltrating cells including B cells and macrophages. B cell-deficient muMT mice showed suppression of AAA development that was associated with reduced activation of Syk and less expression of Mmp9. Administration of exogenous immunoglobulins restored the blunted Syk activation and AAA development in muMT mice. Additionally, exogenous immunoglobulins induced IL-6 and MMP9 secretions in human AAA tissue cultures. Furthermore, administration of R788, a specific Syk inhibitor, suppressed AAA expansion, reduced inflammatory response, and reduced immunoglobulin deposition in AAA tissue. Conclusions—From these results, we concluded that B cells and immunoglobulins participated in AAA pathogenesis by promoting inflammatory and tissue destructive activities. Finally, we identified Syk as a potential therapeutic target.

2018-04-25 | GSE109638 | GEO

Involvement of B cells, immunoglobulins, and Syk in the pathogenesis of abdominal aortic aneurysm II

2018-04-25 | GSE109639 | GEO

Involvement of B cells, immunoglobulins, and Syk in the pathogenesis of abdominal aortic aneurysm

Project description:Involvement of B cells, immunoglobulins, and Syk in the pathogenesis of abdominal aortic aneurysm

| PRJNA431575 | ENA

Harnessing TFEB to treat abdominal aortic aneurysm

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-11-21 | GSE137577 | GEO

Involvement of B cells, immunoglobulins, and Syk in the pathogenesis of abdominal aortic aneurysm II

Project description:Involvement of B cells, immunoglobulins, and Syk in the pathogenesis of abdominal aortic aneurysm II

| PRJNA431588 | ENA

Involvement of B cells, immunoglobulins, and Syk in the pathogenesis of abdominal aortic aneurysm I

Project description:Involvement of B cells, immunoglobulins, and Syk in the pathogenesis of abdominal aortic aneurysm I

| PRJNA431589 | ENA

Pathogenesis and management of abdominal aortic aneurysm.

Project description:Abdominal aortic aneurysm (AAA) causes ∼170 000 deaths annually worldwide. Most guidelines recommend asymptomatic small AAAs (30 to <50 mm in women; 30 to <55 mm in men) are monitored by imaging and large asymptomatic, symptomatic, and ruptured AAAs are considered for surgical repair. Advances in AAA repair techniques have occurred, but a remaining priority is therapies to limit AAA growth and rupture. This review outlines research on AAA pathogenesis and therapies to limit AAA growth. Genome-wide association studies have identified novel drug targets, e.g. interleukin-6 blockade. Mendelian randomization analyses suggest that treatments to reduce low-density lipoprotein cholesterol such as proprotein convertase subtilisin/kexin type 9 inhibitors and smoking reduction or cessation are also treatment targets. Thirteen placebo-controlled randomized trials have tested whether a range of antibiotics, blood pressure-lowering drugs, a mast cell stabilizer, an anti-platelet drug, or fenofibrate slow AAA growth. None of these trials have shown convincing evidence of drug efficacy and have been limited by small sample sizes, limited drug adherence, poor participant retention, and over-optimistic AAA growth reduction targets. Data from some large observational cohorts suggest that blood pressure reduction, particularly by angiotensin-converting enzyme inhibitors, could limit aneurysm rupture, but this has not been evaluated in randomized trials. Some observational studies suggest metformin may limit AAA growth, and this is currently being tested in randomized trials. In conclusion, no drug therapy has been shown to convincingly limit AAA growth in randomized controlled trials. Further large prospective studies on other targets are needed.

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Transcriptional profiling of murine porcine-pancreatic elastase-induced abdominal aortic aneurysm at day 7, with parallel miRNA profiling and miR-24 in vivo modulation.

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-08-31 | E-GEOD-51229 | biostudies-arrayexpress

BAF60a Deficiency in Vascular Smooth Muscle Cells Prevents Abdominal Aortic Aneurysm Formation by Attenuating Vascular Inflammation

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-11-21 | GSE153449 | GEO