Regional cardiac dysfunction is associated with specific alterations in inflammatory cytokines and matrix metalloproteinases after acute myocardial infarction in sheep.
Cardiac remodeling following myocardial infarction (MI) is a maladaptive process, fundamental to the progression of ischemic heart failure. The extent of remodeling is influenced by mechanical stress, inflammatory response and activation of matrix metalloproteinases (MMPs). This study examined regional association between these parameters in response to acute MI. Coronary ligation was performed in ten sheep. Sonomicrometer transducers measured segmental length in the infarcted, border and non-infarcted region. Regional tissue samples obtained 3 h post MI from six sheep were analysed using RT-PCR, gelatin zymography and Western blot. Six sham-operated sheep served as controls.Region-specific dilation and reduced contraction was associated with corresponding alterations in matrix molecules.IL-6 and MMP-9 mRNA were increased in the infarcted and border regions compared to controls.MMP-2 and TIMP-1 mRNA increased in non-infarcted myocardium and both correlated positively with segmental shortening. IL-6 mRNA levels, in contrast, were negatively associated with segmental shortening. In summary, inflammatory cytokines and MMPs are altered early after MI in a region-specific manner, and these changes correspond to acute regional myocardial dysfunction. Therapies for LV remodeling from the time of reperfusion may benefit from further understanding this portfolio of acute alterations.
Gallagher
Gabrielle
G
Cardiac Technology Centre, Dept. of Cardiology and Kolling Institute of Medical Research, Block 4, Level 3, University of Sydney at Royal North Shore Hospital St Leonards, NSW, Australia.
Menzie
Stuart
S
Huang
Yifei
Y
Jackson
Chris
C
Hunyor
Stephen N
SN
D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D015850:Interleukin-6 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009200:Myocardial Contraction / Q000502:physiology*; D009203:Myocardial Infarction / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D012756:Sheep; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
D016207:Cytokines; D015850:Interleukin-6; D019715:Tissue Inhibitor of Metalloproteinase-1; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9