Excessive activation of matrix metalloproteinases coincides with left ventricular remodeling during transition from hypertrophy to heart failure in hypertensive rats
Yoshitaka Iwanaga, MD, PhD*,
Takeshi Aoyama, MD, PhD*,
Yasuki Kihara, MD, PhD, FACC*,*,
Yoko Onozawa, MD*,
Takeshi Yoneda, MD* and
Shigetake Sasayama, MD, PhD, FACC*
* Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
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Figure 1 Results of measurement of tissue inhibitor of matrix metalloproteinase (TIMP) activity in left ventricular extracts of Dahl salt-sensitive (DS) and Dahl salt-resistant (DR) rats at the left ventricular hypertrophy (LVH) and congestive heart failure (CHF) stages. The TIMP activity was measured by reverse zymography. The data are expressed as arbitrary units (values for 11-week-old DR rats were set at 1.0, and remaining values were adjusted accordingly) and mean values ± SEM (n = 8 per group). *p < 0.01; pa = 0.0113; pt = 0.0005; pi = 0.0018. W = weeks.
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Figure 2 Results of measurement of tissue inhibitor of matrix metalloproteinase (TIMP) protein (A) and messenger ribonucleic acid (mRNA) (B) in left ventricular extracts of Dahl salt-sensitive (DS) and Dahl salt-resistant (DR) rats at the left ventricular hypertrophy (LVH) and congestive heart failure (CHF) stages. The TIMP-2 and -4 proteins and mRNA were measured by Western and Northern blot analyses, respectively. The TIMP mRNA level was normalized to that of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA. The data are expressed as arbitrary units (values for 11-week-old DR rats were set at 1.0, and remaining values were adjusted accordingly) and mean values ± SEM. *p < 0.01.  p < 0.05. (A) pa = 0.0207, pt = 0.7292 and pi = 0.0127 for TIMP-2 by Western blot; pa = 0.0002, pt = 0.0002 and pi = 0.0021 for TIMP-4 by Western blot. (B) pa = 0.0746, pt < 0.0001 and pi = 0.1669 for TIMP-2 mRNA by Northern blot; pa = 0.0007, pt = 0.0050 and pi = 0.1804 for TIMP-4 mRNA by Northern blot. W = weeks.
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Figure 3 Gelatin zymography of commercially available matrix metalloproteinase (MMP)-2 and left ventricular (LV) extracts of rats. (A) Results of measurement of MMP activity in LV extracts of Dahl salt-sensitive (DS) and Dahl salt-resistant (DR) rats at the left ventricular hypertrophy (LVH) and congestive heart failure (CHF) stages, and (B) representative gelatin zymograms. (C) We calculated the ratio of the 68- to 72-kDa bands on the zymogram. The data are expressed as arbitrary units (values for 11-week-old DR rats were set at 1.0, and remaining values were adjusted accordingly) and mean values ± SEM (n = 8 per group). *p < 0.01; p < 0.05. (B) pa = 0.061, pt < 0.0001 and pi = 0.0006. (C) pa = 0.0134, pt = 0.0131 and pi = 0.0103. W = weeks.
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Figure 4 Results of measurement of matrix metalloproteinase (MMP)-2 protein (A) and messenger ribonucleic acid (mRNA) (B) in left ventricular (LV) extracts of Dahl salt-sensitive (DS) and Dahl salt-resistant (DR) rats at the left ventricular hypertrophy (LVH) and congestive heart failure (CHF) stages. The MMP-2 proteins and mRNA were measured by Western and Northern blot analyses, respectively. The MMP-2 mRNA level was normalized to that of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA. The data are expressed as arbitrary units (values for 11-week-old DR rats were set at 1.0, and remaining values were adjusted accordingly) and mean values ± SEM. *p < 0.01; p < 0.05. (A) pa = 0.0044, pt = 0.0016 and pi = 0.0026. (B) pa < 0.001, pt < 0.001 and pi = 0.0017. W = weeks.
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