UM206, a frizzled‐receptor antagonist attenuates adverse remodeling and cardiac function deterioration following myocardial infarction (652.10)

Activation of the Wnt/frizzled signaling pathway has a key role in wound healing and cardiac remodeling following myocardial infarction (MI). We have previously shown that Wnt/frizzled signaling blockade with UM206 immediately after MI suppresses adverse remodeling and prevents heart failure (HF) development in a mouse MI model. Here, we investigated the role of UM206 after short-time early treatment and long-term late treatment, in order to unveil the optimal anti-HF regimen. Swiss male mice were subjected to MI by left anterior descending coronary artery permanent ligation. Two different regimens were followed: a) short-time early treatment: 2 weeks of UM206 treatment followed by 3 weeks without treatment and b) long-term late treatment: 3 weeks without treatment followed by 5 weeks of UM206 treatment. UM206 was administered via an osmotic mini-pump (6µg/kg/day) and controls were administered normal saline. Early UM206 treatment led to improved end diastolic volume (178±6 mm3) compared to saline (214±20...