Regional cardiac dysfunction is associated with specific alterations in inflammatory cytokines and matrix metalloproteinases after acute myocardial infarction in sheep |
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Authors: | G Gallagher S Menzie Y Huang C Jackson S N Hunyor |
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Institution: | (1) 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, Sydney (NSW) 2065, Australia;(2) Sutton Arthritis Research Laboratory, University of Sydney at Royal North Shore Hospital St Leonards, Sydney, Australia |
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Abstract: | 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. |
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Keywords: | myocardial contraction extracellular matrix cytokines matrix metalloproteinases myocardial infarction |
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