A Closed-chest Model to Induce Transverse Aortic Constriction in Mice

Eichhorn, Lars; Weisheit, Christina; Gestrich, Christopher; Peukert, Konrad; Duerr, Georg Daniel; Ayub, Muhammad Ajmal; Erdfelder, Felix; Stöckigt, Florian

doi:10.3791/57397

Cited by 12 publications

(11 citation statements)

References 15 publications

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“…To explore the specific role of CXCR1 high Ly6C low macrophages in the development of LV hypertrophy, Cx3cr1 GFP/GFP mice were subjected to a minimal-invasive mouse model of TAC [ 20 ]. Firstly, we evaluated the impact of CX3CR1 expression for the preservation of myocardial function in our model of LV hypertrophy and assessed functional parameters by pressure-volume (PV) measurements 21 days after TAC.…”

Section: Resultsmentioning

confidence: 99%

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CX3CR1 is a prerequisite for the development of cardiac hypertrophy and left ventricular dysfunction in mice upon transverse aortic constriction

et al. 2021

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The CX3CL1/CX3CR1 axis mediates recruitment and extravasation of CX3CR1-expressing subsets of leukocytes and plays a pivotal role in the inflammation-driven pathology of cardiovascular disease. The cardiac immune response differs depending on the underlying causes. This suggests that for the development of successful immunomodulatory therapy in heart failure due to chronic pressure overload induced left ventricular (LV) hypertrophy, the underlying immune patterns must be examined. Here, the authors demonstrate that Fraktalkine-receptor CX3CR1 is a prerequisite for the development of cardiac hypertrophy and left ventricular dysfunction in a mouse model of transverse aortic constriction (TAC). The comparison of C57BL/6 mice with CX3CR1 deficient mice displayed reduced LV hypertrophy and preserved cardiac function in response to pressure overload in mice lacking CX3CR1. Moreover, the normal immune response following TAC induced pressure overload which is dominated by Ly6Clow macrophages changed to an early pro-inflammatory immune response driven by neutrophils, Ly6Chigh macrophages and altered cytokine expression pattern in CX3CR1 deficient mice. In this early inflammatory phase of LV hypertrophy Ly6Chigh monocytes infiltrated the heart in response to a C-C chemokine ligand 2 burst. CX3CR1 expression impacts the immune response in the development of LV hypertrophy and its absence has clear cardioprotective effects. Hence, suppression of CX3CR1 may be an important immunomodulatory therapeutic target to ameliorate pressure-overload induced heart failure.

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Section: Resultsmentioning

confidence: 99%

“…We used a closed-chest model to minimize surgical trauma performing the intervention as microinvasive as possible [ 15 ]. In short, mice where anaesthetized with isoflurane (2 Vol%), intubated with an intubation cannula (OD 1.2 mm).…”

Section: Methodsmentioning

confidence: 99%

CX3CR1 is a prerequisite for the development of cardiac hypertrophy and left ventricular dysfunction in mice upon transverse aortic constriction

et al. 2021

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“…To prevent this, a minimally invasive surgical technique through the 2nd intercostal space was developed, leading to a more rapid recovery of the mice. [17] Minimal invasive surgery was performed in 35% of the included studies. After surgery, 34% of studies mentioned confirmation of the TAC by either echo or invasive pressure measurements.…”

Section: Surgery Characteristicsmentioning

confidence: 99%

The transverse aortic constriction heart failure animal model: a systematic review and meta-analysis

et al. 2020

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The transverse aortic constriction (TAC) model is frequently used to study adverse cardiac remodeling upon pressure overload. We set out to define the most important characteristics that define the degree of cardiac remodeling in this model. A systematic review and meta-analyses were performed on studies using the TAC mouse/rat model and reporting echocardiographic outcome parameters. We included all animal studies in which a constriction around the transverse aorta and at least one of the predefined echocardiography or MRI outcome parameters were assessed. A total of 502 articles and > 3000 wild-type, untreated animals undergoing TAC were included in this study and referenced to a control group. The duration of aortic constriction correlated to the degree of adverse remodeling. However, the mouse data is strongly biased by the preferential use of male C57Bl/6 mice (66% of studies). Furthermore, mostly ketamine/xylazine anesthetics, 27G needle constriction, and silk sutures are used. Nonetheless, despite the homogeneity in experimental design, the model contained a substantial degree of heterogeneity in the functional outcome measures. When looking at study quality, only 12% reported randomization, 23% mentioned any sort of blinding, 25% adequately addressed the outcomes, and an amazingly low percentage (2%) showed sample size calculation. Meta-analyses did not detect specific study characteristics that explained the heterogeneity in the reported outcome measures, however this might be related to the strong bias towards the use of specific mouse lines, sex as well as age or to poor reporting of characteristics of study quality.

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“…Sham-operated mice were subjected to the same procedure but without banding. One week after the operation, mice were subject to ultrasound to examine whether the TAC model was successfully established according to previously reported standards ( 14 , 15 ). Two weeks later, mice were sacrificed by anesthesia overdosing with intra-peritoneal injection of pentobarbital sodium and cervical dislocation, and their ascending aortas were collected for further analysis.…”

Section: Methodsmentioning

confidence: 99%

Identification of Transcriptional Variation in Aortic Remodeling Using a Murine Transverse Aortic Constriction (TAC) Model

Zhang

Feng

Zeng

et al. 2020

Front. Cardiovasc. Med.

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Arterial remodeling is a major pathological consequence of hypertension, which is recognized as the most common chronic non-communicable disease. However, the detailed mechanism of how arterial remodeling is induced by hypertension has not yet been fully elucidated. Evaluating the transcriptional changes in arterial tissue in response to elevated blood pressure at an early stage may provide new insights and identify novel therapeutic candidates in preventing arterial remodeling. Here, we used the ascending aorta of the transverse aortic constriction (TAC) model to induce arterial remodeling in C57BL/6 male mice. Age-matched mice were subjected to sham surgery as controls. The TAC model was only considered successful if the mice conformed to the criteria (RC/LC blood flow velocity with 5–10-fold change) 1 week after the surgery. Two weeks after surgery, the ascending aorta developed severe remodeling in TAC mice as compared to the sham group. High throughput sequencing was then applied to identify differentially expressed (DE) transcripts. In silicon analysis were then performed to systematically network transcriptional changes. A total of 1,019 mRNAs were significantly changed between TAC and the sham group at the transcriptional level. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis revealed that stress/stimulus/immune-related biological processes played a crucial role during arterial remodeling. Our data provide a comprehensive understanding of global gene expression changes in the TAC model, which suggests that targeting inflammation and vascular smooth cell transformation are potential therapeutic strategies to interfere with the aortic remodeling at an early stage in the development of hypertension.

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A Closed-chest Model to Induce Transverse Aortic Constriction in Mice

Cited by 12 publications

References 15 publications

CX3CR1 is a prerequisite for the development of cardiac hypertrophy and left ventricular dysfunction in mice upon transverse aortic constriction

CX3CR1 is a prerequisite for the development of cardiac hypertrophy and left ventricular dysfunction in mice upon transverse aortic constriction

The transverse aortic constriction heart failure animal model: a systematic review and meta-analysis

Identification of Transcriptional Variation in Aortic Remodeling Using a Murine Transverse Aortic Constriction (TAC) Model

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