主动脉弓缩窄（Transverse aortic constriction，TAC）是一个慢性心室肥大的最为常用疾病模型，可用于模拟高血压或室内压增高而引起的肥厚性心肌病，在临床前药物研究或基础医学、生物学研究中广泛应用。TAC模型是指通过外科手术的方式对横向主动脉进行结扎造成固定大小的缩窄来实现。主动脉缩窄术后，心脏后负荷增大，前期表现为代偿性肥大，而后逐渐发展成心肌肥厚和心力衰竭。与永久性结扎左冠状动脉前降支导致的心力衰竭相比，TAC提供了心脏肥大的可再现模型及心力衰竭中发展更缓慢渐进的时间过程。主动脉的缩窄程度决定了心脏肥大的发展程度及心衰和心室扩张的发展时间进程。TAC手术后即刻诱发/启动心室肥厚的进程，根据不同的小鼠品系和手术缩窄程度（如27G、28G缩窄），心室肥厚和心衰进展速度也不一样。一般来说1周（28G缩窄）或2周（27G缩窄）即可发展为显著性的心室肥厚，并可于2~3周（28G缩窄）或4~6周（27G缩窄）发展为心力衰竭。
造摸方法：通过颈正中开口分离主动脉周围组织，结扎横主动脉和垫针后，将垫针撤出缝合肌肉及皮肤。
Fig.1. The Process of Ligating the Transverse Aortic Arch. A) The aortic arch is clearly visible. B) Using the aforementioned hook needle, separate the aortic arch from the nearby connective tissue. C) Using the hooked needle, guide the suture under the aortic arch, and with the use of a spacer, tie a constriction of the desired diameter. D) Completed ligation.
模型评估及检测：
1、心脏超声：术前、术后不同阶段对心脏结构、功能作全面的评估（心室室壁的厚度、心腔的直径、心室的容积、射血分数EF%、短轴缩短分数FS%等）；
2、用压力导管或压力-容积导管，做左血流动力学测试（如左室的收缩压、舒张压、收缩容积、舒张容积等）；
3、采集血样进行血生化检测；
4、采集心肺样本，计算心脏/体重比，肺/体重比；
5、心肺样本病理及分子检测。
Fig.2.Color and Pulsed-wave Doppler Ultrasound Imaging from the Aortic Arch of Ligated and Non-ligated Mice. A) Color Doppler imaging of the aortic arch of a non-ligated mouse. The two carotid arteries are clearly visible, as well as the lack of a constriction between them. B) Aortic peak flow velocity of a non-ligated mouse. C) Color Doppler imaging of the aortic arch of a ligated mouse. The constriction between the two carotid arteries on the aortic arch is visible (yellow arrowheads). D) Peak flow velocity at the constriction site.
Fig.3.Representative Whole Heart Images Following TAC. A. Sham-operated wild type mouse heart. B. Wild type mouse heart 16 weeks post-TAC. Each line = 1mm.
Fig.4. BET Bromodomain inhibition attenuates cardinal histopathologic features of HF (A) CM area quantification in LV sections. Bar=30µm. (B) Trichrome staining and quantification of fibrotic area. Bar=400µm (top), 40µm (bottom). (C) TUNEL staining of heart sections with quantification of TUNEL-positive nuclei. Bar=20 µm.
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