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Atorvastatin Improves Ventricular Remodeling after Myocardial Infarction by Interfering with Collagen Metabolism

View Article: PubMed Central - PubMed

ABSTRACT

Purpose: Therapeutic strategies that modulate ventricular remodeling can be useful after acute myocardial infarction (MI). In particular, statins may exert effects on molecular pathways involved in collagen metabolism. The aim of this study was to determine whether treatment with atorvastatin for 4 weeks would lead to changes in collagen metabolism and ventricular remodeling in a rat model of MI.

Methods: Male Wistar rats were used in this study. MI was induced in rats by ligation of the left anterior descending coronary artery (LAD). Animals were randomized into three groups, according to treatment: sham surgery without LAD ligation (sham group, n = 14), LAD ligation followed by 10mg atorvastatin/kg/day for 4 weeks (atorvastatin group, n = 24), or LAD ligation followed by saline solution for 4 weeks (control group, n = 27). After 4 weeks, hemodynamic characteristics were obtained by a pressure-volume catheter. Hearts were removed, and the left ventricles were subjected to histologic analysis of the extents of fibrosis and collagen deposition, as well as the myocyte cross-sectional area. Expression levels of mediators involved in collagen metabolism and inflammation were also assessed.

Results: End-diastolic volume, fibrotic content, and myocyte cross-sectional area were significantly reduced in the atorvastatin compared to the control group. Atorvastatin modulated expression levels of proteins related to collagen metabolism, including MMP1, TIMP1, COL I, PCPE, and SPARC, in remote infarct regions. Atorvastatin had anti-inflammatory effects, as indicated by lower expression levels of TLR4, IL-1, and NF-kB p50.

Conclusion: Treatment with atorvastatin for 4 weeks was able to attenuate ventricular dysfunction, fibrosis, and left ventricular hypertrophy after MI in rats, perhaps in part through effects on collagen metabolism and inflammation. Atorvastatin may be useful for limiting ventricular remodeling after myocardial ischemic events.

No MeSH data available.


Related in: MedlinePlus

Histological Images Showing LVs of Animals in the Three Groups.Sham (A and D), control (B and E), and atorvastatin groups (C and F). Sections were stained with Masson trichrome for fibrosis analysis (top) or Picro Sirius red for collagen analysis (bottom). Scale bars: 1000μm. Histograms show that the percentage of fibrosis in the LV was reduced after treatment with atorvastatin (white), without affecting the collagen content, compared to the control group (black). Sham group (gray) showed less collagen deposition compared to the atorvastatin and control groups. Data are expressed as the mean ± SD. *P<0.05 versus sham group, #P<0.05 versus control group.
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pone.0166845.g001: Histological Images Showing LVs of Animals in the Three Groups.Sham (A and D), control (B and E), and atorvastatin groups (C and F). Sections were stained with Masson trichrome for fibrosis analysis (top) or Picro Sirius red for collagen analysis (bottom). Scale bars: 1000μm. Histograms show that the percentage of fibrosis in the LV was reduced after treatment with atorvastatin (white), without affecting the collagen content, compared to the control group (black). Sham group (gray) showed less collagen deposition compared to the atorvastatin and control groups. Data are expressed as the mean ± SD. *P<0.05 versus sham group, #P<0.05 versus control group.

Mentions: We quantified areas of fibrosis and collagen deposition on the LV in the three groups (Fig 1). Animals subjected to LAD ligation showed larger areas of fibrosis compared to animals subjected to sham surgery (sham: 1.1% ± 0.3%, control: 20.8% ± 7.6%, atorvastatin: 15.0% ± 6.7%; P<0.01). Treatment with atorvastatin for 4 weeks reduced the area of fibrosis compared to the control group (P = 0.03). We found smaller areas of collagen deposition in the LVs of rats in the sham group compared to groups with LAD ligation (sham: 0.81% ± 0.31%, control: 9.5% ± 5.0%, atorvastatin: 7.4% ± 4.5%; P<0.01). No significant difference in the extent of collagen deposition was observed between the control and atorvastatin groups (P = 0.24).


Atorvastatin Improves Ventricular Remodeling after Myocardial Infarction by Interfering with Collagen Metabolism
Histological Images Showing LVs of Animals in the Three Groups.Sham (A and D), control (B and E), and atorvastatin groups (C and F). Sections were stained with Masson trichrome for fibrosis analysis (top) or Picro Sirius red for collagen analysis (bottom). Scale bars: 1000μm. Histograms show that the percentage of fibrosis in the LV was reduced after treatment with atorvastatin (white), without affecting the collagen content, compared to the control group (black). Sham group (gray) showed less collagen deposition compared to the atorvastatin and control groups. Data are expressed as the mean ± SD. *P<0.05 versus sham group, #P<0.05 versus control group.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5120826&req=5

pone.0166845.g001: Histological Images Showing LVs of Animals in the Three Groups.Sham (A and D), control (B and E), and atorvastatin groups (C and F). Sections were stained with Masson trichrome for fibrosis analysis (top) or Picro Sirius red for collagen analysis (bottom). Scale bars: 1000μm. Histograms show that the percentage of fibrosis in the LV was reduced after treatment with atorvastatin (white), without affecting the collagen content, compared to the control group (black). Sham group (gray) showed less collagen deposition compared to the atorvastatin and control groups. Data are expressed as the mean ± SD. *P<0.05 versus sham group, #P<0.05 versus control group.
Mentions: We quantified areas of fibrosis and collagen deposition on the LV in the three groups (Fig 1). Animals subjected to LAD ligation showed larger areas of fibrosis compared to animals subjected to sham surgery (sham: 1.1% ± 0.3%, control: 20.8% ± 7.6%, atorvastatin: 15.0% ± 6.7%; P<0.01). Treatment with atorvastatin for 4 weeks reduced the area of fibrosis compared to the control group (P = 0.03). We found smaller areas of collagen deposition in the LVs of rats in the sham group compared to groups with LAD ligation (sham: 0.81% ± 0.31%, control: 9.5% ± 5.0%, atorvastatin: 7.4% ± 4.5%; P<0.01). No significant difference in the extent of collagen deposition was observed between the control and atorvastatin groups (P = 0.24).

View Article: PubMed Central - PubMed

ABSTRACT

Purpose: Therapeutic strategies that modulate ventricular remodeling can be useful after acute myocardial infarction (MI). In particular, statins may exert effects on molecular pathways involved in collagen metabolism. The aim of this study was to determine whether treatment with atorvastatin for 4 weeks would lead to changes in collagen metabolism and ventricular remodeling in a rat model of MI.

Methods: Male Wistar rats were used in this study. MI was induced in rats by ligation of the left anterior descending coronary artery (LAD). Animals were randomized into three groups, according to treatment: sham surgery without LAD ligation (sham group, n = 14), LAD ligation followed by 10mg atorvastatin/kg/day for 4 weeks (atorvastatin group, n = 24), or LAD ligation followed by saline solution for 4 weeks (control group, n = 27). After 4 weeks, hemodynamic characteristics were obtained by a pressure-volume catheter. Hearts were removed, and the left ventricles were subjected to histologic analysis of the extents of fibrosis and collagen deposition, as well as the myocyte cross-sectional area. Expression levels of mediators involved in collagen metabolism and inflammation were also assessed.

Results: End-diastolic volume, fibrotic content, and myocyte cross-sectional area were significantly reduced in the atorvastatin compared to the control group. Atorvastatin modulated expression levels of proteins related to collagen metabolism, including MMP1, TIMP1, COL I, PCPE, and SPARC, in remote infarct regions. Atorvastatin had anti-inflammatory effects, as indicated by lower expression levels of TLR4, IL-1, and NF-kB p50.

Conclusion: Treatment with atorvastatin for 4 weeks was able to attenuate ventricular dysfunction, fibrosis, and left ventricular hypertrophy after MI in rats, perhaps in part through effects on collagen metabolism and inflammation. Atorvastatin may be useful for limiting ventricular remodeling after myocardial ischemic events.

No MeSH data available.


Related in: MedlinePlus