MCIP1 overexpression reduced post-MI left ventricular mass increase by 38% compared to wild-type mice, preserving LV geometry and contractility.
Does MCIP1 overexpression prevent pathological left ventricular remodeling and preserve cardiac function after myocardial infarction in mice?
Cardiac-specific overexpression of MCIP1 inhibits calcineurin activation, thereby suppressing pathological left ventricular remodeling and preserving cardiac function after myocardial infarction in mice.
Pathological remodeling of the left ventricle (LV) after myocardial infarction (MI) is a major cause of heart failure. Although cardiac hypertrophy after increased loading conditions has been recognized as a clinical risk factor for human heart failure, it is unknown whether post-MI hypertrophic remodeling of the myocardium is beneficial for cardiac function over time, nor which regulatory pathways play a crucial role in this process. To address these questions, transgenic (TG) mice engineered to overexpress modulatory calcineurin-interacting protein-1 (MCIP1) in the myocardium were used to achieve cardiac-specific inhibition of calcineurin activation. MCIP1-TG mice and their wild-type (WT) littermates, were subjected to MI and analyzed 4 weeks later. At 4 weeks after MI, calcineurin was activated in the LV of WT mice, which was significantly reduced in MCIP1-TG mice. WT mice displayed a 78% increase in LV mass after MI, which was reduced by 38% in MCIP1-TG mice. Echocardiography indicated marked LV dilation and loss of systolic function in WT-MI mice, whereas TG-MI mice displayed a remarkable preservation of LV geometry and contractility, a pronounced reduction in myofiber hypertrophy, collagen deposition, and beta-MHC expression compared with WT-MI mice. Together, these results reveal a protective role for MCIP1 in the post-MI heart and suggest that calcineurin is a crucial regulator of postinfarction-induced pathological LV remodeling. The improvement in functional, structural, and molecular abnormalities in MCIP1-TG mice challenges the adaptive value of post-MI hypertrophy of the remote myocardium. The full text of this article is available online at http://circres.ahajournals.org.
Rooij et al. (Tue,) conducted a other in Myocardial infarction. MCIP1 overexpression vs. Wild-type littermates was evaluated on Left ventricular mass increase and remodeling. MCIP1 overexpression reduced post-MI left ventricular mass increase by 38% compared to wild-type mice, preserving LV geometry and contractility.