Limits...
Simvastatin inhibited cardiac hypertrophy and fibrosis in apolipoprotein E-deficient mice fed a "Western-style diet" by increasing PPAR α and γ expression and reducing TC, MMP-9, and Cat S levels.

Qin YW, Ye P, He JQ, Sheng L, Wang LY, Du J - Acta Pharmacol. Sin. (2010)

Bottom Line: The simvastatin treatment group showed significantly reduced LV wall thickness, myocardial cell diameters and LV collagen content at 40 weeks when compared with the control group (P<0.05).Furthermore, treatment with simvastatin also significantly inhibited the mRNA and protein expressions of MMP-9 and Cat S as well as increased the mRNA and protein expressions of PPAR alpha and PPAR gamma at 32 and 40 weeks compared with the control group (P<0.05).Simvastatin treatment inhibits the development of cardiac hypertrophy and fibrosis, and this effect may be mediated through increased levels of PPAR alpha and PPAR gamma and reduced levels of TC, MMP-9, and Cat S.

View Article: PubMed Central - PubMed

Affiliation: Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, China.

ABSTRACT

Aim: The examine the cardiac hypertrophy and fibrosis in apolipoprotein E-deficient mice (ApoE-/- mice) fed a "Western-style diet" and the effect of simvastatin intervention.

Methods: Male ApoE-/- mice (n=36) were fed a "Western-style diet" from the age of 8 weeks. After 16 weeks, they were randomly given either simvastatin (25 mg·kg⁻¹·d⁻¹) or normal saline (control group) by gavage for 8, 16, or 24 weeks. The left ventricular (LV) wall thickness and diameter of the myocardial cells were determined with Hematoxylin-Eosin stain, and the level of fibrosis of the myocardial matrix was assessed with Masson stain. Real-time quantitative polymerase chain reaction and Western blotting analysis were used to determine the mRNA and protein expression of matrix metalloproteinase-9 (MMP-9), Cathepsin S (Cat S), and the peroxisome proliferator-activated receptors (PPARs) in the myocardium of ApoE-/- mice.

Results: ApoE-/- mice fed a "Western-style diet" showed an significant age-dependent increase in total cholesterol (TC), LV wall thickness, myocardial cell diameter and LV collagen content (P<0.05). The simvastatin treatment group showed significantly reduced LV wall thickness, myocardial cell diameters and LV collagen content at 40 weeks when compared with the control group (P<0.05). Furthermore, treatment with simvastatin also significantly inhibited the mRNA and protein expressions of MMP-9 and Cat S as well as increased the mRNA and protein expressions of PPAR alpha and PPAR gamma at 32 and 40 weeks compared with the control group (P<0.05).

Conclusion: ApoE-/- mice fed a "Western-style diet" had cardiac hypertrophy and fibrosis, which worsened with age. Simvastatin treatment inhibits the development of cardiac hypertrophy and fibrosis, and this effect may be mediated through increased levels of PPAR alpha and PPAR gamma and reduced levels of TC, MMP-9, and Cat S.

Show MeSH

Related in: MedlinePlus

Comparison of the levels of fibrosis in the LV myocardium between the control (A: 24 weeks,C: 32 weeks,E: 40 weeks) and simvastatin-treated (B: 24 weeks, D:32 weeks, F: 40 weeks) ApoE−/− mice fed a “Western-style diet”. Sections were stained using Masson's trichrome and visualized at 100× magnification. Red indicates muscle fibers, blue indicates collagen, and black indicates nuclei. The control group showed an age-dependent increase in the LV collagen volume fraction, which was significantly inhibited by simvastatin at 32 and 40 weeks. Representative micrographs and the LV collagen volume fraction quantitative data are shown. The quantitative data are given as means±SD. bP<0.05, significant difference between the control and simvastatin groups of the same age. eP<0.05, significant difference between control groups of different ages.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4012913&req=5

fig2: Comparison of the levels of fibrosis in the LV myocardium between the control (A: 24 weeks,C: 32 weeks,E: 40 weeks) and simvastatin-treated (B: 24 weeks, D:32 weeks, F: 40 weeks) ApoE−/− mice fed a “Western-style diet”. Sections were stained using Masson's trichrome and visualized at 100× magnification. Red indicates muscle fibers, blue indicates collagen, and black indicates nuclei. The control group showed an age-dependent increase in the LV collagen volume fraction, which was significantly inhibited by simvastatin at 32 and 40 weeks. Representative micrographs and the LV collagen volume fraction quantitative data are shown. The quantitative data are given as means±SD. bP<0.05, significant difference between the control and simvastatin groups of the same age. eP<0.05, significant difference between control groups of different ages.

Mentions: The LV collagen content also showed an age-dependent increase in the control mice (P<0.05). The collagen volume fraction was reduced in the simvastatin group (0.20±0.02 vs 0.29±0.01 at 32 weeks, 0.31±0.02 vs 0.40±0.01 at 40 weeks; P<0.05) compared with that of the control group. Representative micrographs of Masson trichrome staining of the LV to determine the extent of fibrosis are shown in Figure 2.


Simvastatin inhibited cardiac hypertrophy and fibrosis in apolipoprotein E-deficient mice fed a "Western-style diet" by increasing PPAR α and γ expression and reducing TC, MMP-9, and Cat S levels.

Qin YW, Ye P, He JQ, Sheng L, Wang LY, Du J - Acta Pharmacol. Sin. (2010)

Comparison of the levels of fibrosis in the LV myocardium between the control (A: 24 weeks,C: 32 weeks,E: 40 weeks) and simvastatin-treated (B: 24 weeks, D:32 weeks, F: 40 weeks) ApoE−/− mice fed a “Western-style diet”. Sections were stained using Masson's trichrome and visualized at 100× magnification. Red indicates muscle fibers, blue indicates collagen, and black indicates nuclei. The control group showed an age-dependent increase in the LV collagen volume fraction, which was significantly inhibited by simvastatin at 32 and 40 weeks. Representative micrographs and the LV collagen volume fraction quantitative data are shown. The quantitative data are given as means±SD. bP<0.05, significant difference between the control and simvastatin groups of the same age. eP<0.05, significant difference between control groups of different ages.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4012913&req=5

fig2: Comparison of the levels of fibrosis in the LV myocardium between the control (A: 24 weeks,C: 32 weeks,E: 40 weeks) and simvastatin-treated (B: 24 weeks, D:32 weeks, F: 40 weeks) ApoE−/− mice fed a “Western-style diet”. Sections were stained using Masson's trichrome and visualized at 100× magnification. Red indicates muscle fibers, blue indicates collagen, and black indicates nuclei. The control group showed an age-dependent increase in the LV collagen volume fraction, which was significantly inhibited by simvastatin at 32 and 40 weeks. Representative micrographs and the LV collagen volume fraction quantitative data are shown. The quantitative data are given as means±SD. bP<0.05, significant difference between the control and simvastatin groups of the same age. eP<0.05, significant difference between control groups of different ages.
Mentions: The LV collagen content also showed an age-dependent increase in the control mice (P<0.05). The collagen volume fraction was reduced in the simvastatin group (0.20±0.02 vs 0.29±0.01 at 32 weeks, 0.31±0.02 vs 0.40±0.01 at 40 weeks; P<0.05) compared with that of the control group. Representative micrographs of Masson trichrome staining of the LV to determine the extent of fibrosis are shown in Figure 2.

Bottom Line: The simvastatin treatment group showed significantly reduced LV wall thickness, myocardial cell diameters and LV collagen content at 40 weeks when compared with the control group (P<0.05).Furthermore, treatment with simvastatin also significantly inhibited the mRNA and protein expressions of MMP-9 and Cat S as well as increased the mRNA and protein expressions of PPAR alpha and PPAR gamma at 32 and 40 weeks compared with the control group (P<0.05).Simvastatin treatment inhibits the development of cardiac hypertrophy and fibrosis, and this effect may be mediated through increased levels of PPAR alpha and PPAR gamma and reduced levels of TC, MMP-9, and Cat S.

View Article: PubMed Central - PubMed

Affiliation: Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, China.

ABSTRACT

Aim: The examine the cardiac hypertrophy and fibrosis in apolipoprotein E-deficient mice (ApoE-/- mice) fed a "Western-style diet" and the effect of simvastatin intervention.

Methods: Male ApoE-/- mice (n=36) were fed a "Western-style diet" from the age of 8 weeks. After 16 weeks, they were randomly given either simvastatin (25 mg·kg⁻¹·d⁻¹) or normal saline (control group) by gavage for 8, 16, or 24 weeks. The left ventricular (LV) wall thickness and diameter of the myocardial cells were determined with Hematoxylin-Eosin stain, and the level of fibrosis of the myocardial matrix was assessed with Masson stain. Real-time quantitative polymerase chain reaction and Western blotting analysis were used to determine the mRNA and protein expression of matrix metalloproteinase-9 (MMP-9), Cathepsin S (Cat S), and the peroxisome proliferator-activated receptors (PPARs) in the myocardium of ApoE-/- mice.

Results: ApoE-/- mice fed a "Western-style diet" showed an significant age-dependent increase in total cholesterol (TC), LV wall thickness, myocardial cell diameter and LV collagen content (P<0.05). The simvastatin treatment group showed significantly reduced LV wall thickness, myocardial cell diameters and LV collagen content at 40 weeks when compared with the control group (P<0.05). Furthermore, treatment with simvastatin also significantly inhibited the mRNA and protein expressions of MMP-9 and Cat S as well as increased the mRNA and protein expressions of PPAR alpha and PPAR gamma at 32 and 40 weeks compared with the control group (P<0.05).

Conclusion: ApoE-/- mice fed a "Western-style diet" had cardiac hypertrophy and fibrosis, which worsened with age. Simvastatin treatment inhibits the development of cardiac hypertrophy and fibrosis, and this effect may be mediated through increased levels of PPAR alpha and PPAR gamma and reduced levels of TC, MMP-9, and Cat S.

Show MeSH
Related in: MedlinePlus