np-031112 and Atrial-Remodeling

A key feature of acute myocardial infarction (AMI) is an alteration in cardiac architecture. Signaling events that result in the inhibition of glycogen synthase kinase-3 (GSK-3)β represent an adaptive response that might limit the extent of adverse remodeling in the aftermath of AMI. Here, we report that an allosteric inhibitor of GSK-3β, 4-benzyl-2-(naphthalene-1-yl)-1,2,4-thiadiazolidine-3,5-dione (NP12), lessens the magnitude of adverse myocardial remodeling and promotes angiogenesis. Male and female mice 8-10 weeks old were grouped (six animals in each group) into sham surgery (sham group), left anterior descending (LAD) ligation of the coronary artery followed by intramyocardial PBS injections (control group), and LAD ligation followed by NP12 administration (NP12 group). After 7 and 14 days, the extents of fibrosis and integrity of blood vessels were determined. Intramyocardial administration of NP12 increased phosphorylation of GSK-3β, reduced fibrosis, and restored diastolic function in the mice that had experienced an AMI. Morphometric analyses revealed increased CD31

Topics: Allosteric Regulation; Angiogenesis Inducing Agents; Animals; Aorta; Apoptosis; Atrial Remodeling; Coronary Vessels; Disease Models, Animal; Female; Glycogen Synthase Kinase 3; Heart Ventricles; In Vitro Techniques; Ligation; Male; Mice, Inbred BALB C; Mice, Inbred C57BL; Myocardial Infarction; Neovascularization, Physiologic; Phosphorylation; Protein Kinase Inhibitors; Protein Processing, Post-Translational; Thiadiazoles