??ARK1 Inhibition Improves Survival in a Mouse Model of Heart Failure Induced by Myocardial Infarction

Yoshiyuki Suzuki, Kiyotaka Nakano, Masakazu Sugiyama, Jun-ichi Imagawa
2004 Journal of Cardiovascular Pharmacology  
Heart failure (HF) is characterized by abnormalities in ␤-adrenergic receptor (␤AR) signaling, including an increase in ␤AR kinase 1 (␤ARK1) levels and activity. Gene therapy using a peptide inhibitor of ␤ARK1 (␤ARKct) in infarcted rabbit hearts has improved compromised cardiac function. To determine whether ␤ARK1 inhibition improves survival in a mouse model of HF induced by myocardial infarction (MI), we studied wild-type (WT) and transgenic (TG) mice overexpressing ␤ARKct following MI. There
more » ... following MI. There was no difference in infarct size. Survival of WT mice with MI was 25% at 26 weeks. In contrast, 92% of ␤ARKct TG mice with MI survived (P = 0.01). ␤ARKct TG mice with MI at 8 weeks showed significantly higher fractional shortening compared with WT mice with MI (25.1 ± 2.7% versus 14.2 ± 1.0%; P < 0.05). Moreover, the biochemical ␤AR abnormalities in WT mice with MI were prevented in ␤ARKct TG mice with MI. In conclusion, ␤ARK1 inhibition results in a marked increase in survival and improved cardiac function in a mouse model of HF induced by MI. Echocardiography was performed at 8 weeks after MI. Compared with the respective sham-operated mice, LVEDD and LVESD were significantly increased, and FS was reduced Suzuki et al Values are expressed as mean ± SEM. BW, body weight; HW, heart weight; LVW, left ventricular (LV) weight; RVW, right ventricular weight; LVEDD, LV end diastolic dimension; LVESD, LV end systolic dimension; AWth, anterior wall thickness; PWth, posterior wall thickness; HR, heart rate; FS, fractional shortening. *P < 0.05 vs. respective sham; †P < 0.05 vs. respective WT (Bonferroni/Dunn test).
doi:10.1097/01.fjc.0000134776.70798.44 pmid:15475830 fatcat:4qvvkwazsvazfmosmxeymh44cm