Abstract 17857: Doxycycline Prevents Interleukin-1 Induced Left Ventricular Systolic Dysfunction in the Mouse
Background: Interleukin-1 (IL-1) impairs myocardial contractility. We hypothesized that activation of MMP-2 in the heart following IL-1 leads to degradation of Troponin I and subsequent impaired contractility.
Methods: Two months old CD-1 mice were randomly assigned to four different groups (n=8/group): i) sham vehicle treated mice; ii) recombinant murine IL-1β (rmIL-1β; 3mcg/Kg); iii) 30 minutes pre-treatment with a MMP-2 inhibitor, doxycycline (1.5mg/Kg) followed by IL-1β; iv) doxycycline alone. Changes in cardiac function were measured by transthoracic echocardiography at 4 hours. cTnI serum levels were evaluated by ELISA and a gelatin zymography was used to determine MMP-2 levels in the heart and in the serum.
Results: rmIL-1β mice lead to a significant reduction in left ventricular (LV) fractional shortening (FS) associated with a significant increase of cTnI circulating levels in rmIL-1β mice (0.73±0.38 ng/ml vs sham 0.027±0.013; p=0.05) and with an increase in the MMP-2 activity in the heart and serum, compared to sham treated mice. Treatment with doxycycline, a MMP-2 inhibitor, prevented IL-1β-induced LV systolic dysfunction (Figure).
Conclusions: IL-1β induces MMP-2 activation in the mouse heart, and doxycycline, a MMP-2 inhibitor, prevents IL-1β induced systolic dysfunction. .
- © 2012 by American Heart Association, Inc.