bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2022.04.12.488011

Inflammation induced Vascular Smooth Muscle Cell expressing Angiopoietin-like 2 to promote the development of abdominal aortic aneurysm

Yang, G.·Guo, J.·Wu, S.·Yu, H.
View original source ↗Export metadata ↓

Abstract

ObjectiveThe objective of this study is to investigate the expression of angiopoietin-like protein 2 (Angptl2) in abdominal aortic aneurysm (AAA) and the expression of Angptl2 in vascular smooth muscle cells (VSMC) under inflammation stimuli. MethodsThe mouse AAA model was induced by applying calcium chloride method based the literature and the expression of Angptl2 in AAA was investigated by immunohistochemical staining. The primary VSMCs were cultured and identified following with inflammatory stimuli by Escherichia coli lipopolysaccharide (LPS) for 30 minutes and 24 hours. The expression of Angptl2 were assessed by RT-qPCR and ELISA. ResultsThe mouse AAA model was successfully established after being induced by calcium chloride. The inflammatory cell infiltration in the arterial tissue of the mice in the experimental group was obvious, and the elastic fiber layer was thinned and broken. Immunohistochemical staining showed that the expression of Angptl2 in AAA was up-regulated; After LPS treatment, both the mRNA and protein expressions of Angptl2 were significantly up-regulated in VSMCs in the experimental group compared with control group. ConclusionAngptl2 expressed in VSMCs promotes the development of calcium chloride induced AAA.

Explore related subjects

pathologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Yang, G., Guo, J., Wu, S., Yu, H.. 2022-04-13. Inflammation induced Vascular Smooth Muscle Cell expressing Angiopoietin-like 2 to promote the development of abdominal aortic aneurysm. https://doi.org/10.1101/2022.04.12.488011

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

NAE1-Dependent Protein Neddylation Preserves Endothelial Identity and Vascular Integrity

Background: Endothelial dysfunction is a central driver of cardiovascular and inflammatory diseases, yet the post-translational mechanisms that preserve endothelial homeostasis remain incompletely understood. Protein neddylation, the covalent conjugation of a ubiquitin-like modifier, regulates diverse cellular processes, yet its physiological role in the vascular endothelium remains unknown. This study investigated whether protein neddylation is required to preserve endothelial identity and vascular homeostasis. Methods: We generated tamoxifen-inducible endothelial-specific Nae1 knockout mice to inhibit neddylation and combined bulk RNA sequencing, single-cell and single-nucleus transcriptomics, quantitative proteomics, biochemical analyses, and gain- and loss-of-function approaches to define the role of endothelial neddylation in vascular homeostasis and inflammatory injury. Results: Endothelial-specific Nae1 deletion caused rapid mortality associated with vascular leakage, platelet accumulation, inflammation, and multi-organ injury. Multi-omics analyses demonstrated profound loss of endothelial identity, characterized by suppression of core endothelial programs and activation of inflammatory, procoagulant, and pyroptotic pathways. Single-cell analyses revealed progressive endothelial dysfunction culminating in depletion of the endothelial population and remodeling of the vascular niche. Mechanistically, endothelial neddylation deficiency activated gasdermin D (GSDMD)- and gasdermin E (GSDME)-dependent pyroptosis, whereas dual inhibition of GSDMD and GSDME markedly attenuated inflammatory transcriptomic remodeling, vascular injury, hepatocyte death, immune cell infiltration, and platelet accumulation. Translational analyses demonstrated reduced endothelial neddylation in experimental endotoxemia and decreased expression of neddylation pathway components in human atherosclerosis and COVID-19 datasets. Conversely, restoration of endothelial neddylation partially reversed inflammatory endothelial transcriptomic reprogramming in vivo. Conclusions: NAE1-dependent protein neddylation is an essential regulator of endothelial identity and vascular integrity. Loss of endothelial neddylation promotes gasdermin-dependent pyroptosis and thrombo-inflammatory vascular injury, whereas restoration of the neddylation pathway mitigates inflammatory endothelial dysfunction. These findings identify endothelial neddylation as a fundamental mechanism maintaining vascular homeostasis and a potential therapeutic target for cardiovascular and inflammatory diseases.

pathology↗
bioRxiv2023

Age-related phenotypes in breast cancer: a population- based study

Breast cancer in young (<40 years) is associated with a higher frequency of aggressive tumor types and poor prognosis. It remains unclear if there is an underlying age-related biology that contributes to the unfavorable outcome. We aim to investigate the relationship between age and breast cancer biology, with emphasis on proliferation. Clinico-pathologic information, immunohistochemical markers, and follow-up data were obtained for all patients aged <50 (Bergen cohort-1; n=355) and compared to previously obtained information on patients aged 50-69 (Bergen cohort-2; n=540), who participated in the Norwegian Breast Cancer Screening Program. Data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) was applied for validation and for analyses of gene expression signatures. Young breast cancer patients presented more aggressive tumor features such as hormone receptor negativity, HER2 positivity, lymph-node metastasis, the HER2-enriched and triple negative subtypes, and shorter survival. Age <40 was significantly associated with features of stemness and higher proliferation (by Ki67), also in molecular subsets. Ki67 showed weaker prognostic value in young patients. We point to aggressive phenotypes, increased tumor cell proliferation and stem-like features in breast cancer of the young. Hence, tumors of young breast cancer patients may have a unique biology, also when accounting for screen/interval differences, that may open for new clinical opportunities, stratifying treatment by age.

pathology↗
bioRxiv2023

New semi-automated tool for the quantitation of MR imaging to estimate in vivo muscle disease severity in mice

The pathology in Duchenne muscular dystrophy (DMD) is characterized by degenerating muscle fibers, inflammation, fibro-fatty infiltrate, and edema, and these pathological processes replace normal healthy muscle tissue. The mdx mouse model is one of the most commonly used preclinical models to study DMD. Mounting evidence has emerged illustrating that muscle disease progression varies considerably in mdx mice, with inter-animal differences as well as intra-muscular differences in pathology in individual mdx mice. This variation is important to consider when conducting assessments of drug efficacy and in longitudinal studies. Magnetic resonance imaging (MRI) is a non-invasive method that can be used qualitatively or quantitatively to measure muscle disease progression in the clinic and in preclinical models. Although MR imaging is highly sensitive, image acquisition and analysis can be time intensive. The purpose of this study was to develop a semi-automated muscle segmentation and quantitation pipeline that can quickly and accurately estimate muscle disease severity in mice. Herein, we show that the newly developed segmentation tool accurately divides muscle. We show that measures of skew and interdecile range based on segmentation sufficiently estimate muscle disease severity in healthy wildtype and diseased mdx mice. Moreover, the semi-automated pipeline reduced analysis time by nearly 10-fold. Use of this rapid, non-invasive, semi-automated MR imaging and analysis pipeline has the potential to transform preclinical studies, allowing for pre-screening of dystrophic mice prior to study enrollment to ensure more uniform muscle disease pathology across treatment groups, improving study outcomes.

pathology↗