The TAC model is a previously published, reproducible model of HF predominantly due to pressure overload23. The sudden onset of hypertension achieved by TAC causes both an approximately 50% increase in LV mass within the first 2-4 weeks, and a well-defined HF phenotype by 12 weeks. Following intubation and mechanical ventilation of the mice, the transverse aorta was accessed through partial thoracotomy via the upper edge of the sternum. The transverse aorta was dissected free from surrounding tissues and then ligated together with a small piece of a blunted, 27-gauge needle parallel to the aorta, using a 7-0 silk thread. The 27-gauge needle was then removed to yield an approximate 0.4 mm constriction of the inner aortic diameter. Following incision closure, mice were allowed to recover and were monitored for 8 weeks with monthly echocardiograms. Mouse hearts were harvested at 8 weeks after TAC and were either snap-frozen in liquid nitrogen or fixed in 10% formalin for further studies.
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