O-ring-induced transverse aortic constriction (OTAC) is a new simple method to develop cardiac hypertrophy and heart failure in mice

Yasuhisa Nakao,Tomohisa Sakaue,Osamu Yamaguchi,Kayo Takahashi,Shuntaro Ikeda,Jun Aono,Mika Hamaguchi,Katsuji Inoue

doi:10.1038/s41598-021-04096-9

Abstract

Suture-based transverse aortic constriction (TAC) in mice is one of the most frequently used experimental models for cardiac pressure overload-induced heart failure. However, the incidence of heart failure in the conventional TAC depends on the operator’s skill. To optimize and simplify this method, we proposed O-ring-induced transverse aortic constriction (OTAC) in mice. C57BL/6J mice were subjected to OTAC, in which an o-ring was applied to the transverse aorta (between the brachiocephalic artery and the left common carotid artery) and tied with a triple knot. We used different inner diameters of o-rings were 0.50 and 0.45 mm. Pressure overload by OTAC promoted left ventricular (LV) hypertrophy. OTAC also increased lung weight, indicating severe pulmonary congestion. Echocardiographic findings revealed that both OTAC groups developed LV hypertrophy within one week after the procedure and gradually reduced LV fractional shortening. In addition, significant elevations in gene expression related to heart failure, LV hypertrophy, and LV fibrosis were observed in the LV of OTAC mice. We demonstrated the OTAC method, which is a simple and effective cardiac pressure overload method in mice. This method will efficiently help us understand heart failure (HF) mechanisms with reduced LV ejection fraction (HFrEF) and cardiac hypertrophy.

Highlights

Suture-based transverse aortic constriction (TAC) in mice is one of the most frequently used experimental models for cardiac pressure overload-induced heart failure
This study demonstrated an innovative method to induce cardiac pressure overload using the O-ring-induced transverse aortic constriction (OTAC) technique in mice
This method can be performed without intubation and is highly reproducible for simulating cardiac hypertrophy, fibrosis, and HFrEF (Tables 1 and 3)

Summary

Introduction

Suture-based transverse aortic constriction (TAC) in mice is one of the most frequently used experimental models for cardiac pressure overload-induced heart failure. Transverse aortic constriction (TAC) (Fig. 1A–C) in mice is widely used to induce pressure overload, resulting in concentric hypertrophy, interstitial fibrosis, and increased LV stiffness, eventually leading to systolic and diastolic heart failure[9,10,11,12,13]. This model is considered an excellent experimental tool for understanding the mechanisms of HF and cardiac hypertrophy over the past two decades. The TAC model showed a more gradual progression of hypertrophy compared to the ascending aortic constriction model

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Conclusion