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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

Myocyte Cross-sectional Areas in Remote Regions of LV Infarcts.Images correspond to sham (A), control (B), and atorvastatin groups (C). Scale bars: 100μm. Sections were stained with H&E. Seventy cells were analyzed per plate (n = 14 animals per group). 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.g003: Myocyte Cross-sectional Areas in Remote Regions of LV Infarcts.Images correspond to sham (A), control (B), and atorvastatin groups (C). Scale bars: 100μm. Sections were stained with H&E. Seventy cells were analyzed per plate (n = 14 animals per group). Data are expressed as the mean ± SD. *P<0.05 versus sham group, #P<0.05 versus control group.

Mentions: To evaluate the extent of ventricular hypertrophy, we analyzed the myocyte cross-sectional area in histological sections of remote regions of the infarcts from animals in the three groups (Fig 3). After 4 weeks, we found significantly smaller myocyte cross-sectional areas in the sham compared to the control or atorvastatin group (sham: 209.6 ± 45.34 μm, control: 446.8 ± 133.0 μm, atorvastatin: 261.1 ± 79.35 μm; P<0.01), as well as in the atorvastatin compared to the control group (P<0.01).


Atorvastatin Improves Ventricular Remodeling after Myocardial Infarction by Interfering with Collagen Metabolism
Myocyte Cross-sectional Areas in Remote Regions of LV Infarcts.Images correspond to sham (A), control (B), and atorvastatin groups (C). Scale bars: 100μm. Sections were stained with H&E. Seventy cells were analyzed per plate (n = 14 animals per group). 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

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

pone.0166845.g003: Myocyte Cross-sectional Areas in Remote Regions of LV Infarcts.Images correspond to sham (A), control (B), and atorvastatin groups (C). Scale bars: 100μm. Sections were stained with H&E. Seventy cells were analyzed per plate (n = 14 animals per group). Data are expressed as the mean ± SD. *P<0.05 versus sham group, #P<0.05 versus control group.
Mentions: To evaluate the extent of ventricular hypertrophy, we analyzed the myocyte cross-sectional area in histological sections of remote regions of the infarcts from animals in the three groups (Fig 3). After 4 weeks, we found significantly smaller myocyte cross-sectional areas in the sham compared to the control or atorvastatin group (sham: 209.6 ± 45.34 μm, control: 446.8 ± 133.0 μm, atorvastatin: 261.1 ± 79.35 μm; P<0.01), as well as in the atorvastatin compared to the control group (P<0.01).

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