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Tissue Inhibitor of Metalloproteinase‐1 Levels Predict Left Ventricular Dilation following Myocardial Infarction in Mice
Author(s) -
Escobar Gladys Patricia,
Dai Qiuxia,
Lindsey Merry
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.585.2
Subject(s) - ventricle , myocardial infarction , medicine , timp1 , periostin , cardiology , ventricular remodeling , extracellular matrix , heart failure , tissue inhibitor of metalloproteinase , infarction , endocrinology , matrix metalloproteinase , gene expression , chemistry , gene , biochemistry
Myocardial infarction (MI) is a leading cause of congestive heart failure. Currently, biomarkers to predict adverse left ventricle (LV) remodeling post‐MI are lacking. The objective was to evaluate extracellular matrix (ECM) and adhesion molecule (AM) gene levels post‐MI to determine biomarkers of LV remodeling. We evaluated unoperated (n=6) and 7 days post‐MI mice (n=7) by echocardiography. Remote non‐infarcted (LVR) and infarct region (LVI) were examined and compared to unoperated LV control (LVC). RT2 profiler PCR array for ECM and AM was used to determine differentially expressed gene levels in post‐MI LV. The most upregulated gene was α1 collagen I, which increased from 6.0±0.2 normalized threshold cycles (ΔCt) in LVC to 2.6±0.8 normalized ΔCt in LVR to 0.5±0.9 normalized ΔCt in LVI (p<0.001 between all groups). The square of the Pearson product moment correlation coefficients were calculated for end diastolic dimensions (EDD) (y) and gene levels (x). Positive correlations were found for α1 collagen I (R=0.70), α1 collagen II (R=0.72), periostin (R=0.70), and tissue inhibitor of metalloproteinase‐1 (TIMP‐1; R=0.70; all p<0.001). Plasma TIMP‐1 levels increased from 0.83±0.05 ng/mL in LVC mice to 3.70±0.63 ng/mL and MI mice (p<0.01). Plasma TIMP‐1 levels correlated significantly with EDD (R=0.697; p<0.001). Together, our data suggest TIMP‐1 is a useful plasma biomarker for LV diastolic dimension changes.