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TAC animal model of aortic arch coarctation


TAC animal model of aortic arch coarctation

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Pathological cardiac hypertrophy
Cardiovascular disease model

Pathological cardiac hypertrophy

Introduction to TAC Animal Models

The transverse aortic constriction (TAC) model is a well-established surgical model of hypertrophic cardiomyopathy. By constricting the aortic arch, the TAC model replicates cardiac hypertrophy resulting from increased hemodynamic overload and the subsequent transition to chronic heart failure, mimicking the pathophysiology of human heart failure caused by hypertension or aortic valve stenosis.

Advantages of Aniphe BioLab’s TAC Animal Model Platform Services

This platform boasts mature TAC model‑building and comprehensive evaluation capabilities, with robust technology and a well‑integrated infrastructure, enabling efficient execution of related research and drug‑development activities.

 Comprehensive model coverage

The modeling technique is highly sophisticated.

Precise surgical constriction of the aortic arch is employed, with minimally invasive techniques that minimize animal trauma, resulting in a high model success rate and excellent reproducibility.

 Standardization of the modeling process

Typical model phenotype

It can stably reproduce pathological conditions such as myocardial hypertrophy, ventricular remodeling, myocardial fibrosis, and heart failure, which closely mirror the clinical manifestations.

 Multidimensional Evaluation System

A comprehensive testing system is in place.

It is capable of conducting multidimensional assessments, including cardiac ultrasound, hemodynamic studies, pathological staining, and molecular biology analyses.

 Adaptable to multi-cycle studies

Flexible, customized solutions

The degree of narrowing and the observation period can be adjusted as needed to accommodate different research objectives.

 Standardization of Data Delivery

One-stop closed-loop service

The entire experimental process is conducted in-house, eliminating the need for external collaboration, thereby significantly shortening project timelines and meeting diverse research and regulatory‑compliance reporting requirements.

Modeling cycle

1 week, 2–3 weeks, 4–6 weeks

1  Laboratory animals

C57 (mouse) SD (rat)

1  Positive drug

There is no single specific positive drug; treatment is typically selected based on mechanism: RAAS inhibitors (ACEIs/ARBs, such as captopril, enalapril, valsartan, and losartan) serve as the core standard for demonstrating improvements in myocardial remodeling, while β‑blockers, aldosterone antagonists, and SGLT2 inhibitors are used as complementary controls to modulate sympathetic activity, inhibit fibrosis, and exert metabolic effects.

1  Application areas

It is primarily used to investigate the pathogenic mechanisms underlying pressure-overload–induced cardiac hypertrophy, myocardial fibrosis, and chronic heart failure; to screen for anti‑cardiac remodeling and anti‑heart failure agents; and to evaluate their efficacy and safety. In addition, it supports the identification of drug targets and the development of candidate therapeutics, making it well suited for both basic research and preclinical studies, including IND submissions.

Experimental results

Construction of TAC animal models

Eight- to ten-week-old C57 male mice and three- to four-week-old SD male rats were selected, each subjected to a one-week acclimatization period. Following isoflurane anesthesia, the neck was prepared by shaving and disinfecting; the skin was incised and the underlying tissues dissected to expose the aortic arch. A needle of appropriate gauge was then applied against the vessel and used to perform ligation, after which the needle was removed to establish vascular stenosis. In the sham‑operation group, only the same procedural steps were carried out without performing ligation.

 

 

Model features:

01 No need to use a small-animal ventilator.

In the absence of mechanical ventilation, the incidence of severe airway‑related complications, such as laryngeal edema and asphyxia caused by tracheal intubation, is reduced.

02 Does not damage the sternum

Because the intercostal approach does not injure the sternum, it avoids damage to the thoracic wall vessels, significantly reduces intraoperative blood loss, and provides a clear surgical field.

03 Minimally invasive surgery features small incisions and minimal tissue trauma.

The chest closure and skin suturing procedures are straightforward, resulting in markedly improved postoperative outcomes compared with the conventional technique. There is no thoracic deformity, and the animals exhibit rapid recovery, low perioperative mortality, excellent reproducibility, and a high success rate.

04 The method is easy to operate.

This method can be performed using only basic surgical instruments, and a skilled operator can complete the TAC procedure within 5 minutes.

Cardiac phenotype

Following TAC surgery, mice typically develop cardiac hypertrophy within 1–2 weeks; by 4 weeks, marked cardiac enlargement is evident, with significant increases in the heart-to-body weight ratio and the heart-to-tibial length ratio, consistent with a myocardial hypertrophy phenotype.

 

 

Echocardiographic Imaging Examination

Compared with the control group, the mice exhibited significantly reduced cardiac contractile function, marked thickening of the left ventricular wall, and significant increases in both the systolic diameter and internal diameter of the left ventricle, along with a substantial rise in left ventricular mass—features consistent with a myocardial hypertrophy phenotype.

 

 

HE staining results

In vitro cardiac assessments of mice following TAC modeling revealed a marked increase in heart size, thickening of the ventricular walls, and mild myocardial fibrosis.

 

 

Precautions

The construction of the rat aortic arch constriction model is similar to that in mice; an appropriately sized suture and needle should be selected based on the rat’s body weight. Compared with mice, establishing this model in rats is somewhat more challenging, as the rat aortic arch lies deeper and is more difficult to locate.

In addition, during the model‑establishment process, the following points should also be taken into account:

01 Without ventilator support, anesthesia should not be too deep; the animal’s responsiveness should be diminished, but it should still exhibit a response to strong stimuli applied to the extremities.

02 When performing sternal incision, the first cut should be slightly偏向 to the right, and the second cut must not extend beyond the second rib; otherwise, pneumothorax may easily occur.

03 During thymus dissection, maneuvers should be gentle to avoid excessive traction that could damage the pleura. If the pleura is inadvertently injured, the resulting change in intrathoracic negative pressure will cause lung collapse, leading to immediate death of the animal.

04 When passing the suture beneath the aortic arch, avoid inserting it too deeply; otherwise, there is a risk of perforating the pulmonary artery or the pleura, leading to massive hemorrhage or pneumothorax.

05 The tension applied during aortic arch ligation should not be excessive; it should be just sufficient to allow the pledget‑suture needle to be withdrawn smoothly. Otherwise, the aorta may be torn during ligation, or the aortic arch may be damaged when the pledget‑suture needle is removed.

06 Do not house the animal with others until it has fully regained consciousness, to prevent chest injuries and bleeding caused by being trampled.