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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

Immunoblotting Results for Expression Levels of Proteins Related to Collagen Metabolism in Remote Regions of LV Infarcts.Representative blots for expression levels of each studied protein. Bands corresponding to each protein (top) were normalized by Ponceau staining (red bands on bottom). Histograms show expression levels determined by densitometry. Data are expressed as the mean ± SD. *P<0.05 versus sham group; #P<0.05 versus control group. Data are representative of nine animals per group.
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pone.0166845.g004: Immunoblotting Results for Expression Levels of Proteins Related to Collagen Metabolism in Remote Regions of LV Infarcts.Representative blots for expression levels of each studied protein. Bands corresponding to each protein (top) were normalized by Ponceau staining (red bands on bottom). Histograms show expression levels determined by densitometry. Data are expressed as the mean ± SD. *P<0.05 versus sham group; #P<0.05 versus control group. Data are representative of nine animals per group.

Mentions: We studied expression levels of proteins related to collagen metabolism (i.e., MMP-1/8, TIMP1, COL I, COL III, PCPE, and SPARC) in remote regions of LV infarcts from animals in the three groups (Fig 4). The atorvastatin group showed significantly higher MMP-1/8 and TIMP1 but lower COL I expression levels compared to the control group. We found significantly lower expression levels of PCPE and SPARC in the atorvastatin group compared to the control group. The COL III level did not significantly differ among the three groups. Taken together, these results show that atorvastatin treatment strongly influenced collagen metabolism in the LV infarcts.


Atorvastatin Improves Ventricular Remodeling after Myocardial Infarction by Interfering with Collagen Metabolism
Immunoblotting Results for Expression Levels of Proteins Related to Collagen Metabolism in Remote Regions of LV Infarcts.Representative blots for expression levels of each studied protein. Bands corresponding to each protein (top) were normalized by Ponceau staining (red bands on bottom). Histograms show expression levels determined by densitometry. Data are expressed as the mean ± SD. *P<0.05 versus sham group; #P<0.05 versus control group. Data are representative of nine animals per group.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0166845.g004: Immunoblotting Results for Expression Levels of Proteins Related to Collagen Metabolism in Remote Regions of LV Infarcts.Representative blots for expression levels of each studied protein. Bands corresponding to each protein (top) were normalized by Ponceau staining (red bands on bottom). Histograms show expression levels determined by densitometry. Data are expressed as the mean ± SD. *P<0.05 versus sham group; #P<0.05 versus control group. Data are representative of nine animals per group.
Mentions: We studied expression levels of proteins related to collagen metabolism (i.e., MMP-1/8, TIMP1, COL I, COL III, PCPE, and SPARC) in remote regions of LV infarcts from animals in the three groups (Fig 4). The atorvastatin group showed significantly higher MMP-1/8 and TIMP1 but lower COL I expression levels compared to the control group. We found significantly lower expression levels of PCPE and SPARC in the atorvastatin group compared to the control group. The COL III level did not significantly differ among the three groups. Taken together, these results show that atorvastatin treatment strongly influenced collagen metabolism in the LV infarcts.

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