title: Early postmyocardial infarction survival in Murphy Roths Large mice is mediated by attenuated apoptosis and inflammation but depends on genetic background.
abstract: The Murphy Roths Large (MRL) mouse, a strain capable of regenerating right ventricular myocardium, has a high postmyocardial infarction (post-MI) survival rate compared with C57BL/6J (C57) mice. The biological processes responsible for this survival advantage are unknown. To assess the effect of genetic background, the LG/J strain, which harbours 75% of the MRL composite genome, was included in the study. The MRL survival advantage versus C57 mice (92 versus 68%, P < 0.05) occurred primarily in the first 5 days; LG/J survival was intermediate (P = n.s.). Microarray data analysis revealed an attenuation of apoptotic (P < 0.05) and stress response transcripts in MRL hearts compared with C57 hearts post-MI. Supporting the microarray results, there were fewer TUNEL-positive cells 1 day post-MI in MRL infarcts compared with C57 infarcts (P = 0.001) and fewer CD45-positive cells in the MRL infarct border zone 2 days post-MI (P < 0.01); the LG/J results were intermediate (P = n.s.). The MRL hearts had smaller infarct scars and attenuated ventricular dilatation 30 days post-MI compared with C57 hearts (P < 0.05). We conclude that the early post-MI survival advantage of MRL mice over the C57 strain is mediated at least in part by reductions in apoptosis and inflammatory infiltration, and that these reductions may influence chronic remodelling. The intermediate survival, apoptosis and inflammation profile of LG/J mice suggests that this high tolerance for MI in the MRL mouse could be derived from its shared genetic background with the LG/J mouse.
authors.affiliation: Department of Bioengineering, University of California at San Diego, La Jolla, CA, USA.
authors.forename: Darlene L
authors.initials: DL
authors.lastname: Hunt
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Campbell
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Zambon
authors.forename: Karen
authors.initials: K
authors.lastname: Vranizan
authors.forename: Sylvia M
authors.initials: SM
authors.lastname: Evans
authors.forename: Hai-Chien
authors.initials: HC
authors.lastname: Kuo
authors.forename: Ken D
authors.initials: KD
authors.lastname: Yamaguchi
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Omens
authors.forename: Andrew D
authors.initials: AD
authors.lastname: McCulloch
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D004106:Dilatation / Q000379:methods; D006321:Heart / Q000502:physiology; D020287:In Situ Nick-End Labeling / Q000379:methods; D007249:Inflammation / Q000235:genetics*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000235:genetics* / Q000378:metabolism; D015996:Survival Rate; D020257:Ventricular Remodeling / Q000235:genetics*
chemical_list: D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse