Attenuation of the post‐myocardial infarction stress response may promote improved survival and healing in the MRL mouse

Abstract

Introduction: MRL/MpJ (MRL) mice heal better following myocardial infarction (MI) than C57BL/6J (C57) controls, may regenerate cardiac muscle, and have improved long‐term survival, though the mechanisms are unclear. We compared acute post‐MI survival and healing differences between the two strains as well as the LG/J strain, the major genetic background of the MRL. Methods: MI was induced in adult male MRL, LG/J, and C57 mice by permanent ligation of the left coronary artery. Infarct size was measured after 1, 5, or 30 days. Microarray analysis was performed on RNA collected before and 1 or 5 days post‐MI. Survival was tracked through 70 days. Results: Survival was significantly greater in MRL than C57 mice, due to decreased LV rupture in MRLs during days 2–5 post‐infarct. LG/J mice also appear more susceptible to rupture. Infarct size on day 1 was not different between the MRL and C57 strains, but was significantly larger in C57 mice after 30 days. Preliminary results suggest infarcts of all 3 strains expand to a similar degree after 5 days. Microarray analysis indicates the expression of transcripts associated with induction of apoptosis, the immune response, and inhibition of cellular proliferation may be reduced in the MRL day 1 infarct compared to the C57. The relative attenuation of these processes may contribute to the MRL's survival advantage and promote improved healing. Support: NIH