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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

Fibrosis and Collagen Levels in Remote Regions of the LV after MI.Histogram shows that treatment with atorvastatin (white) did not reduce the deposition of fibrosis or collagen compared to the control group (black). Fibrosis content was reduced in animals from the sham group (gray) compared to animals subjected to MI (atorvastatin and control groups). Data are expressed as the mean ± SD. *P<0.05 versus sham group. Data are representative of 14 animals per group.
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pone.0166845.g002: Fibrosis and Collagen Levels in Remote Regions of the LV after MI.Histogram shows that treatment with atorvastatin (white) did not reduce the deposition of fibrosis or collagen compared to the control group (black). Fibrosis content was reduced in animals from the sham group (gray) compared to animals subjected to MI (atorvastatin and control groups). Data are expressed as the mean ± SD. *P<0.05 versus sham group. Data are representative of 14 animals per group.

Mentions: We evaluated the areas of fibrosis and collagen in remote infarct regions for rats in the three groups (Fig 2). Animals in the sham group had smaller areas of fibrosis compared to animals in the control or atorvastatin group (sham: 0.6% ± 0.4%, control: 3.5% ± 2.7%, atorvastatin: 2.6% ± 1.4%; P<0.01). No significant difference in collagen deposition area was found among the three groups (sham: 0.7% ± 0.3%, control: 1.1% ± 0.7%, atorvastatin: 0.9% ± 0.4%; P = 0.14).


Atorvastatin Improves Ventricular Remodeling after Myocardial Infarction by Interfering with Collagen Metabolism
Fibrosis and Collagen Levels in Remote Regions of the LV after MI.Histogram shows that treatment with atorvastatin (white) did not reduce the deposition of fibrosis or collagen compared to the control group (black). Fibrosis content was reduced in animals from the sham group (gray) compared to animals subjected to MI (atorvastatin and control groups). Data are expressed as the mean ± SD. *P<0.05 versus sham group. Data are representative of 14 animals per group.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0166845.g002: Fibrosis and Collagen Levels in Remote Regions of the LV after MI.Histogram shows that treatment with atorvastatin (white) did not reduce the deposition of fibrosis or collagen compared to the control group (black). Fibrosis content was reduced in animals from the sham group (gray) compared to animals subjected to MI (atorvastatin and control groups). Data are expressed as the mean ± SD. *P<0.05 versus sham group. Data are representative of 14 animals per group.
Mentions: We evaluated the areas of fibrosis and collagen in remote infarct regions for rats in the three groups (Fig 2). Animals in the sham group had smaller areas of fibrosis compared to animals in the control or atorvastatin group (sham: 0.6% ± 0.4%, control: 3.5% ± 2.7%, atorvastatin: 2.6% ± 1.4%; P<0.01). No significant difference in collagen deposition area was found among the three groups (sham: 0.7% ± 0.3%, control: 1.1% ± 0.7%, atorvastatin: 0.9% ± 0.4%; P = 0.14).

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