Standardized Mouse Models for Pulmonary Hypertension

All animal experiments were approved by the Institutional Animal Care and Use Committee at Acceleron Pharma Inc., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and performed in accordance with the guidelines from the NIH Guide for the Care and Use of Laboratory Animals. Male C57BL/6 mice (10 weeks old, Jackson Laboratory) were used for TAC and MI models as described (18 (link), 22 (link)), and male Balb/c mice (10 weeks old, Jackson Laboratory) were used for the prolonged TAC model to establish PH. Male obese ZSF1 rats (8 and 23 weeks old) and their lean littermates (Charles River, Wilmington, MA, USA) were used for the PH-HFpEF study. PH was established by a single subcutaneous injection of a vascular endothelial growth factor receptor antagonist, Sugen 5416 (SU5416, 100 mg/kg; Cayman), suspended in CMC buffer (0.5% sodium carboxymethyl cellulose, 0.4% polysorbate 80, 0.9% sodium chloride, and 0.9% benzyl alcohol) (23 (link), 24 (link)). Animals were euthanized in all experiments by heart and lung removal en bloc according to AVMA guidelines.