Mouse strain determines the outcome of wound healing after myocardial infarction.
OBJECTIVE
Our objective was to study the effect of the genetic background on the wound healing process after myocardial infarction (MI) in mice.


RESULTS
MI was induced in five different mouse strains (BalbC, C57Bl6, FVB, 129S6, and Swiss). At 3, 14, and 28 days after MI, cardiac dimensions were monitored by echocardiography and histology, whereas cardiac function was determined by direct intraventricular pressure measurements (dP/dt). Furthermore, matrix metalloproteinases were measured by zymography, and mRNA expression by quantitative PCR. Infarct rupture, which typically occurred at 3-6 days post-MI, was most frequent in 129S6 mice (62%), followed by C57Bl6 (36%), FVB (29%), Swiss (23%), and BalbC (5%). The high incidence of infarct rupture in 129S6 mice was associated with high systolic blood pressure and increased influx of inflammatory cells. Cardiac dilatation was most marked in Swiss mice and least prominent in 129S6 mice. The degree of dilatation was associated with a reduced ejection fraction and decreased dP/dt values at 14 and 28 days post-MI. At day 14 and 28 post-MI, secondary thinning of the infarct area was marked in BalbC, FVB, and Swiss, but absent in C57Bl6 and 129S6 mice. In the latter two groups, this was paralleled by the highest number of myofibroblasts at day 14 post-MI.


CONCLUSIONS
The outcome of infarct healing in mice strongly depends on genetic background. On the basis of our results, we suggest that for studies on infarct rupture, the 129S6 mouse is the background of choice, whereas BalbC and Swiss mice are the preferred models to study infarct thinning post-MI.
van den Borne
Susanne W M
SW
Department of Pharmacology and Toxicology, CARIM, Cardiovascular Research Institute Maastricht, Maastricht University, 50 Universiteitssingel, PO Box 616, 6200 MD Maastricht, The Netherlands.
van de Schans
Veerle A M
VA
Strzelecka
Agnieszka E
AE
Vervoort-Peters
Helena T M
HT
Lijnen
Peter M
PM
Cleutjens
Jack P M
JP
Smits
Jos F M
JF
Daemen
Mat J A P
MJ
Janssen
Ben J A
BJ
Blankesteijn
W Matthijs
WM
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000235:genetics; D001794:Blood Pressure / Q000235:genetics; D004195:Disease Models, Animal; D004452:Echocardiography; D015971:Gene Expression Regulation, Enzymologic; D006342:Heart Rupture, Post-Infarction / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D007249:Inflammation / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology / Q000473:pathology*; D020097:Natriuretic Peptide, Brain / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D013045:Species Specificity; D013318:Stroke Volume / Q000235:genetics; D013997:Time Factors; D016277:Ventricular Function, Left / Q000235:genetics; D017725:Ventricular Pressure / Q000235:genetics; D014945:Wound Healing / Q000235:genetics*
D000959:Antihypertensive Agents; D012333:RNA, Messenger; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D020782:Matrix Metalloproteinases