Dataset Information

Altered IL-32 Signaling in Abdominal Aortic Aneurysm.

ABSTRACT: INTRODUCTION AND OBJECTIVE:Interleukin (IL)-32 is a pro-inflammatory cytokine not previously studied in relation to abdominal aortic aneurysm (AAA). The aim of this study was to elucidate the expression and localization of IL-32 in AAA. METHODS:Expression and localization of IL-32 in human aortic tissue was studied with immunohistochemical analysis and Western blot (AAA: n = 5; controls: n = 4). ELISA was used to measure IL-32 in human plasma samples (AAA: n = 140; controls: n = 37) and in media from cultured peripheral blood mononuclear cells (PBMCs) from 3 healthy donors. IL-32 mRNA in PBMCs, endothelial cells, aortic smooth muscle cells (SMCs), and aortic tissue samples of AAA (n = 16) and control aortas (n = 9) was measured with qPCR. RESULTS:IL-32 was predominantly expressed in SMCs and T-cell-rich areas. Highest mRNA expression was observed in the intima/media layer of the AAA. A weaker protein expression was detected in non-aneurysmal aortas. Expression of IL-32 was confirmed in isolated T cells, macrophages, endothelial cells, and SMCs, where expression was also inducible by cytokines such as interferon-γ. There was no difference in IL-32 expression in plasma between patients and controls. CONCLUSION:IL-32 signaling is altered locally in AAA and could potentially play an important role in aneurysm development. Further studies using animal models would be helpful to study its potential role in AAA disease.

SUBMITTER: Bengts S

PROVIDER: S-EPMC7446302 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Altered IL-32 Signaling in Abdominal Aortic Aneurysm.

Bengts Sophy S Shamoun Levar L Kunath Anne A Appelgren Daniel D Welander Martin M Björck Martin M Wanhainen Anders A Wågsäter Dick D

Journal of vascular research 20200520 4

<h4>Introduction and objective</h4>Interleukin (IL)-32 is a pro-inflammatory cytokine not previously studied in relation to abdominal aortic aneurysm (AAA). The aim of this study was to elucidate the expression and localization of IL-32 in AAA.<h4>Methods</h4>Expression and localization of IL-32 in human aortic tissue was studied with immunohistochemical analysis and Western blot (AAA: n = 5; controls: n = 4). ELISA was used to measure IL-32 in human plasma samples (AAA: n = 140; controls: n = 3 ...[more]

PMID: 32434199

Similar Datasets

Project description:Evidence suggests that the DNA of oral pathogens is detectable in the dilated aortic tissue of abdominal aortic aneurysm (AAA), one of the most fatal cardiovascular diseases. However, the association between oral microbial homeostasis and aneurysm formation remains largely unknown. In this study, a cohort of individuals, including 53 AAA patients and 30 control participants (CTL), was recruited for salivary microbiota investigation by 16S rRNA gene sequencing and bioinformatics analysis. Salivary microbial diversity was decreased in AAA compared with CTL, and the microbial structures were significantly separated between the two groups. Additionally, significant taxonomic and functional changes in the salivary microbiota of AAA participants were observed. The genera Streptococcus and Gemella were remarkably enriched, while Selenomonas, Leptotrichia, Lautropia and Corynebacterium were significantly depleted in AAA. Co-occurrence network analysis showed decreased potential interactions among the differentially abundant microbial genera in AAA. A machine-learning model predicted AAA using the combination of 5 genera and 14 differentially enriched functional pathways, which could distinguish AAA from CTL with an area under the receiver-operating curve of 90.3 %. Finally, 16 genera were found to be significantly positively correlated with the morphological parameters of AAA. Our study is the first to show that AAA patients exhibit oral microbial dysbiosis, which has high predictive power for AAA, and the over-representation of specific salivary bacteria may be associated with AAA disease progression. Further studies are needed to better understand the function of putative oral bacteria in the etiopathogenesis of AAA.ImportanceHost microbial dysbiosis has recently been linked to AAA as a possible etiology. To our knowledge, studies of the oral microbiota and aneurysms remain scarce, although previous studies have indicated that the DNA of some oral pathogens is detectable in aneurysms by PCR method. We take this field one step further by investigating the oral microbiota composition of AAA patients against control participants via high-throughput sequencing technologies and unveiling the potential microbial biomarker associated with AAA formation. Our study will provide new insights into AAA etiology, treatment and prevention from a microecological perspective and highlight the effects of oral microbiota on vascular health.

Project description:BackgroundAbdominal aortic aneurysm (AAA) represents a significant cause of mortality, yet no medical therapies have proven efficacious. The aim of the current study was to leverage human genetic evidence to inform clinical development of IL-6 (interleukin-6) signaling inhibition for the treatment of AAA.MethodsAssociations of rs2228145, a missense variant in the IL6R gene region, are expressed per additional copy of the C allele, corresponding to the genetically predicted effect of IL-6 signaling inhibition. We consider genetic associations with AAA risk in the AAAgen consortium (39 221 cases and 1 086 107 controls) and UK Biobank (1963 cases and 365 680 controls). To validate against known effects of IL-6 signaling inhibition, we present associations with rheumatoid arthritis, polymyalgia rheumatica, and severe COVID-19. To explore mechanism specificity, we present associations with thoracic aortic aneurysm, intracranial aneurysm, and coronary artery disease. We further explored genetic associations in clinically relevant subgroups of the population.ResultsWe observed strong genetic associations with AAA risk in the AAAgen consortium, UK Biobank, and FinnGen (odds ratios: 0.91 [95% CI, 0.90-0.92], P=4×10-30; 0.90 [95% CI, 0.84-0.96], P=0.001; and 0.86 [95% CI, 0.82-0.91], P=7×10-9, respectively). The association was similar for fatal AAA but with greater uncertainty due to the lower number of events. The association with AAA was of greater magnitude than associations with coronary artery disease and even rheumatological disorders for which IL-6 inhibitors have been approved. No strong associations were observed with thoracic aortic aneurysm or intracranial aneurysm. Associations attenuated toward the null in populations with concomitant rheumatological or connective tissue disease.ConclusionsInhibition of IL-6 signaling is a promising strategy for treating AAA but not other types of aneurysmal disease. These findings serve to help inform clinical development of IL-6 signaling inhibition for AAA treatment.

Dataset Information

Altered IL-32 Signaling in Abdominal Aortic Aneurysm.

Publications

Altered IL-32 Signaling in Abdominal Aortic Aneurysm.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets