Dataset Information

Changes in aortic collagen in β-aminopropionitrile-induced acute aortic dissection.

ABSTRACT:

Background

The precise role collagen plays in acute aortic dissection (AAD) was investigated in an animal model of β-aminopropinitrile (BAPN)-induced AAD.

Methods

The 30 3-week-old male specific-pathogen free (SPF)-grade Sprague-Dawley (SD) rats were randomly divided into two groups: 10 in the Control group and 20 in the Model group. The Model group was treated with 0.1% BAPN for 4 weeks, while the Control group received untreated water. Histopathological staining and western blot were used to detect changes of the extracellular matrix (ECM) and collagen content in the aorta.

Results

At the end of the experiment, the incidence of AAD was 25%, the aortic ECM of surviving rats was severely damaged, and the arrangement was disordered. Fibroblast cells are unevenly distributed, with wide gaps, collagen fibers were also distributed unevenly in a disordered arrangement and their thickness was uneven. The elastic membrane disappeared over a large area. Compare to Control group, the Collagen types I, III and their subunits were upregulated (P<0.05), while matrix metalloproteinase (MMP) 2 and MMP9 were downregulated in the aorta of Model group (P<0.05).

Conclusions

In the animal model of BAPN-induced AAD, collagen types I, III and subunits were increased, while MMP2 and MMP9 were decreased in thoracic aorta, which may lead to stiffness of the aorta and be the cause of dissection.

SUBMITTER: Zhou H

PROVIDER: S-EPMC8576682 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Publications

Changes in aortic collagen in β-aminopropionitrile-induced acute aortic dissection.

Zhou Hao H Ren Yan Y Xiao Jun J He Jian J Zhang Yuling Y Qiu Zhihuang Z Huang Qiuyu Q Hu Yunnan Y Chen Liangwan L

Annals of translational medicine 20211001 20

<h4>Background</h4>The precise role collagen plays in acute aortic dissection (AAD) was investigated in an animal model of β-aminopropinitrile (BAPN)-induced AAD.<h4>Methods</h4>The 30 3-week-old male specific-pathogen free (SPF)-grade Sprague-Dawley (SD) rats were randomly divided into two groups: 10 in the Control group and 20 in the Model group. The Model group was treated with 0.1% BAPN for 4 weeks, while the Control group received untreated water. Histopathological staining and western blot ...[more]

PMID: 34790780

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Project description:BackgroundAortic dissection (AD) poses a great threat to the life of patients; however, there is currently no documentation of a clear pathogenic mechanism of this disease. In recent years, β-aminopropionitrile (BAPN)-induced AD in rodents has been widely used in basic research, which provides a good platform for exploring the pathogenesis of AD and drug modification. This study aimed to identify molecular markers and pathways for the diagnosis and treatment of AD by comparing a murine AD model and human AD transcriptome through a bioinformatics analysis.MethodsWe constructed a BAPN-induced mice model and performed high-throughput sequencing analysis. The GSE147026 dataset of patients was obtained from the Gene Expression Omnibus database. We performed a subsequent bioinformatics analysis of human AD and the murine AD model using R software. The DESeq software package was used to analyze the differentially expressed genes (DEGs). Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to analyze the enrichment pathways. Protein-protein interaction network construction and hub gene selection were based on STRING software analysis. Stepwise identification of potential drugs was performed online, while hub genes were validated immunohistochemically.ResultsWe compared the murine AD model and human AD transcriptome and found that both differentially expressed 463 genes. The cytokine-cytokine receptor interaction, tuberculosis, and phagosome pathways were significantly enriched. CDC20, CCNB2, and CCNB1 may be associated with AD development. Protein-drug interactions were also identified.ConclusionsThis study is the first to reveal transcriptional changes in a murine BAPN-induced AD model versus human AD transcriptome. Furthermore, we identified the important hub genes, related pathways, and potential drugs by analyzing the overlapping DEGs between human AD and the murine AD model. Our results provide a basis for the further identification of potential molecular markers for diagnosing and treating AD.

Project description:Acute aortic dissection (AAD) is one of the major aortic diseases that occurs without a preceding symptom and often results in sudden death. Despite the recent advances in cardiovascular medicine, AAD remains a serious problem because its molecular pathogenesis is largely unknown. In this paper, we report our serendipitous discovery that stress-induced expression of tenascin C (TNC), a member of matricellular proteins, is the protection mechanism of aorta to prevent AAD. The aortic wall stress imposed by the aortic stiffening and the angiotensin II infusion caused the strong induction of TNC in wild type mouse aorta without gross morphological changes. While TNC knockout mice at the baseline showed no morphological, histological or biomechanical abnormalities of aorta, deletion of TNC gene rendered the aorta susceptible to AAD upon the aortic stress. The stressed TNC-null aorta showed the loss of the tensile strength due to the insufficient expression of extracellular matrix proteins and the exaggerated proinflammatory response before the onset of AAD. Therefore, TNC works as a stress-activated molecular damper both by reinforcing the tensile strength and by limiting the excessive proinflammatory response in aorta. Thus far, the molecular event that leads to the AAD development has been unclear because of the unpredictable nature of the AAD onset. This study sheds light on the previously unrecognized tissue protection mechanism that converts the potentially harmful stress response into the active reinforcement of the aorta, of which failure leads to the development of AAD. Although TNC is expressed in various tissues upon the mechanical and proinflammatory stimuli, its role has long been a mystery. Our data uncovered the adaptive role of TNC in aorta that must be resilient to the continuous hemodynamic and humoral stress for lifetime. We used periaortic application of 0.5 M CaCl2 to the infrarenal aorta or either wild type (WT) or tenascin C knockout (TNC-KO) mice to create the mouse model for stiffened aorta and infused the mice with AngII (1 µg/min/kg) for 1 week to apply the pathological stress on aorta (Ca+AngII). Mice were then killed with an overdose of pentobarbital to obtain the tissue samples. The suprarenal aortic samples, from the level of right renal artery to 10 mm above the right renal artery, and infrarenal aortic samples, from the level of left renal artery to 10 mm below the left renal artery, were collected and kept in RNAlater (Qiagen) until the extraction of total RNA using RNeasy (Qiagen). We obtained the RNA samples from 8 mice with Ca+AngII treatment and 5 mice without Ca+AngII treatment for each genotype. We pooled the RNA samples with the identical experimental condition to perform the transcriptome analysis using Mouse Genome 430 2.0 (Affymetrix). We obtained suprarenal aortic smooth muscle cells (ASMCs) from TNC-KO mice by enzymatic dispersion and cultured them in Dulbecco's modified Eagle medium (DMEM) supplemented with 10% fetal bovine serum. We cultured TNC-KO ASMCs in the presence or absence of exogenous TNC (10 µg/mL) and stimulated the cells with 10 ng/mL TNF-alpha for 24 h before obtaining total RNA using RNeasy. We used 3 independent ASMC cultures without the exogenous TNC and 4 independent cultures with the exogenous TNC. We hybridized each of the RNA samples individually to Mouse Genome 430 2.0 Array (Affymetrix).

Dataset Information

Changes in aortic collagen in β-aminopropionitrile-induced acute aortic dissection.

Background

Methods

Results

Conclusions

Publications

Changes in aortic collagen in β-aminopropionitrile-induced acute aortic dissection.

Similar Datasets

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