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UM206, a frizzled‐receptor antagonist attenuates adverse remodeling and cardiac function deterioration following myocardial infarction (652.10)
Author(s) -
Hermans Kevin,
Daskalopoulos Evangelos,
Janssen Ben,
Blankesteijn W. Matthijs
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.652.10
Subject(s) - medicine , myocardial infarction , ejection fraction , heart failure , ventricular remodeling , frizzled , saline , cardiology , cardiac function curve , adverse effect , endocrinology , urology , wnt signaling pathway , signal transduction , chemistry , biochemistry
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 mm 3 ) compared to saline (214±20 mm 3 , p<0.01) or to late UM206 treatment (278±24 mm 3 , p<0.01). Both effects were less pronounced compared to the full UM206 treatment (132±30 mm 3 ). Ejection fraction was improved in early (24.4±0.1%) and late (23.2±2.6%) treatment compared to saline (16.5±0.2, p<0.01 and 11.0±3.2%, p<0.05 respectively) but full treatment was the optimal (31.4±0.4%), p<0.001). Both short‐time early and long‐term late UM206‐treatment regimens demonstrate a cardioprotective effect by halting the progression to HF. Nevertheless, full UM206 treatment immediately after MI is the one eliciting the most beneficial effects for the injured myocardium. Grant Funding Source : Supported by the Dutch Heart foundation (2010B196) and Cyttron (FES0908)