Left and right ventricle late remodeling following myocardial infarction in rats.

BACKGROUND: The mechanisms involved in cardiac remodeling in left (LV) and right ventricles (RV) after myocardial infarction (MI) are still unclear. We assayed factors involved in collagen turnover in both ventricles following MI in rats either presenting signs of heart failure (pulmonary congestion and increased LVEDP) or not (INF-HF or INF, respectively). METHODS: MI was induced in male rats by ligation of the left coronary artery. Four weeks after MI gene expression of collagen I, connective tissue growth factor (CTGF), transforming growth factor β (TGF-β) and lysyl oxidase (LOX), metalloproteinase-2 (MMP2) and tissue inhibitor metalloproteinase-2 (TIMP2) as well as cardiac hemodynamic in both ventricles were evaluated. RESULTS: Ventricular dilatation, hypertrophy and an increase in interstitial fibrosis and myocyte size were observed in the RV and LV from INF-HF animals, whereas only LV dilatation and fibrosis in RV was present in INF. The LV fibrosis in INF-HF was associated with higher mRNA of collagen I, CTGF, TGF-β and LOX expressions than in INF and SHAM animals, while MMP2/TIMP2 mRNA ratio did not change. RV fibrosis in INF and INF-HF groups was associated with an increase in LOX mRNA and a reduction in MMP2/TIMP2 ratio. CTGF mRNA was increased only in the INF-HF group. CONCLUSIONS: INF and INF-HF animals presented different patterns of remodeling in both ventricles. In the INF-HF group, fibrosis seems to be consequence of collagen production in LV, and by reductions in collagen degradation in RV of both INF and INF-HF animals

Metalloproteinase-2 (MMP-2, A and B), tissue inhibitor metalloproteinase-2 (TIMP-2, C and D) mRNA levels and MMP-2/TIMP-2 mRNA ratio (E and F) in left (A, C and E) and right ventricle (B, D and F) of sham-operated rats (SHAM) and infarcted animals with (INF-HF) or without heart failure (INF) 30 days after ligation of left coronary artery.

<p>Results were normalized by 18S expression levels. Data are mean ± S.E.M. *p<0.05 vs. SHAM group; ^# p<0.05 vs INF group.</p

Collagen content in left (A) and right ventricle (B) of sham operated rats (SHAM) and infarcted animals with (INF-HF) or without heart failure (INF) 30 days after ligation of left coronary artery.

<p>Bottom panel (C and D) shows representative photomicrographs of Sirius red-stained ventricular tissue sections for all groups (magnification x40). Data are mean ± S.E.M. *p<0.05 vs. SHAM group; ^# p<0.05 vs INF group.</p

Cardiac myocyte cross-sectional area from left (A) and right ventricle (B) of sham-operated rats (SHAM) and infarcted animals with (INF-HF) or without heart failure (INF) 30 days after ligation of left coronary artery.

<p>Bottom panel (C and D) shows representative photomicrographs of hematoxilin-eosin-stained ventricular tissue sections for all groups (magnification x40). Data are mean ± S.E.M., *p<0.05 vs. SHAM group; ^# p<0.05 vs INF group.</p

Collagen I (A and B), transforming growth factor-β (TGF-β; C and D), connective tissue growth factor (CTGF; E and F) and lysyl oxidase (LOX; G and H) mRNA levels in left (A, C, E and G) and right ventricle (B, D, F and H) of sham operated rats (SHAM) and infarcted animals with (INF-HF) or without heart failure (INF) 30 days after ligation of left coronary artery.

<p>Results were normalized by 18S expression levels. Data are mean ± S.E.M. *p<0.05 vs. SHAM group; ^# p<0.05 vs INF group.</p

Scatter plots of the correlations between (A) mRNA levels of transforming growth factor-β (TGF-β) and connective tissue growth factor (CTGF); (B) mRNA levels of transforming growth factor-β (TGF-β) and left ventricle end diastolic pressure (LVEDP) and (C) mRNA levels of interleukin 1 beta (IL-1β) and left ventricle end diastolic pressure (LVEDP) in left ventricle of sham-operated rats (SHAM) and infarcted animals with (INF-HF) or without heart failure (INF) 30 days after ligation of left coronary artery.

<p>Scatter plots of the correlations between (A) mRNA levels of transforming growth factor-β (TGF-β) and connective tissue growth factor (CTGF); (B) mRNA levels of transforming growth factor-β (TGF-β) and left ventricle end diastolic pressure (LVEDP) and (C) mRNA levels of interleukin 1 beta (IL-1β) and left ventricle end diastolic pressure (LVEDP) in left ventricle of sham-operated rats (SHAM) and infarcted animals with (INF-HF) or without heart failure (INF) 30 days after ligation of left coronary artery.</p

General characteristics.

<p>Body weight, relative weight of left (LV/BW) and right ventricle (LV/BW), relative weight of lungs (LW/BW), the weight ratio of right to left ventricles plus interventricular septum (RV/LV+SW), scar size, systolic (SBP) and diastolic (DBP) blood pressure, heart rate, left (LVSP)and right (RVSP) ventricle systolic pressure, left (LVEDP) and right (RVEDP) end diastolic pressure, positive (+dP/dt) and negative (-dP/dt) rates of pressure development in left (LV) and right (RV)ventricle of sham operated rats (SHAM) and infarcted animals with heart failure (INF-HF) with or without heart failure (INF) after 30 days after ligation of left coronary artery. Data are mean ± S.E.M. *<i>p</i><0.05 compared to SHAM. ^#<i>p</i><0.05 compared to INF group.</p

Primers and probes used in quantitative real-time PCR Analysis.

*<p>TaqMan™ Gene expression Assay (Applied Biosystems).</p

Interleukin-1β (IL-1β) mRNA levels in left (A) and right ventricle (B) of sham-operated rats (SHAM) and infarcted animals with (INF-HF) or without heart failure (INF) 30 days after ligation of left coronary artery.

<p>Results were normalized by 18S expression levels. Data are mean ± S.E.M. *p<0.05 vs. SHAM group; ^# p<0.05 vs INF group.</p