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Atorvastatin Reduces Accumulation of Vascular Smooth Muscle Cells to Inhibit Intimal Hyperplasia via p38 MAPK Pathway
Tianshu Chu1, Molin Huang1, Zhiwei Zhao1
1Department of cardiac Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei - China.
Background:
The rate of saphenous vein graft failure one year after coronary artery bypass grafting ranges from 10% to 25%. The aim of this study was to explore whether atorvastatin can reduce accumulation of vascular smooth muscle cells to inhibit intimal hyperplasia via p38 MAPK pathway inhibition.
Methods:
Forty-five Sprague-Dawley rats were randomized to three groups. Thirty rats received a vein graft operation, and they were randomized to be treated with vehicle or atorvastatin; fifteen rats received a sham operation. We detected intimal hyperplasia by hematoxylin-eosin staining and related protein expression by immunohistochemical and Western blot analysis. Comparisons were analyzed by single-factor analysis of variance and Fisher's least significant difference test, with p < 0.05 considered significant.
Results:
The intima analyzed by hematoxylin-eosin staining was dramatically thicker in the control group than in the atorvastatin group and sham group (p < 0.01). The outcomes of immunohistochemical staining of α-SMA demonstrated that the percentage of α-SMA-positive cells in the control group was higher than in the atorvastatin group (p < 0.01). We also evaluated α-SMA, PCNA, p38 MAPK, and phosphorylation of p38 MAPK after statin treatment by Western blot analysis, and the results indicated that atorvastatin did not lead to p38 MAPK reduction (p < 0.05); it did, however, result in inhibition of p38 MAPK phosphorylation (p < 0.01), and it significantly reduced α-SMA and PCNA levels, in comparison with the control group (p < 0.01).
Conclusion:
We have demonstrated that atorvastatin can inhibit accumulation of vascular smooth muscle cells by inhibiting the p38 MAPK pathway, and it is capable of inhibiting intimal hyperplasia in a rat vein graft model.
Insights
Atorvastatin effectively inhibits intimal hyperplasia in a rat vein graft model by reducing vascular smooth muscle cell accumulation. This occurs through the inhibition of the p38 mitogen-activated protein kinase (MAPK) pathway, a key factor in graft failure.
Area of Science:
- Cardiovascular Science
- Pharmacology
- Vascular Biology
Background:
- Saphenous vein graft failure after coronary artery bypass grafting affects 10-25% of patients within one year.
- Intimal hyperplasia, a major cause of graft failure, involves vascular smooth muscle cell accumulation.
- The p38 MAPK pathway is implicated in the development of intimal hyperplasia.
Purpose of the Study:
- To investigate the efficacy of atorvastatin in preventing intimal hyperplasia.
- To determine if atorvastatin inhibits vascular smooth muscle cell accumulation via p38 MAPK pathway inhibition.
- To evaluate atorvastatin's effect on intimal hyperplasia in a rat vein graft model.
Main Methods:
- Forty-five Sprague-Dawley rats were used, randomized into three groups: vein graft with vehicle, vein graft with atorvastatin, and sham operation.
- Intimal hyperplasia was assessed using hematoxylin-eosin staining.
- Protein expression of α-SMA, PCNA, p38 MAPK, and phosphorylated p38 MAPK was analyzed via immunohistochemical and Western blot analysis.
Main Results:
- Atorvastatin treatment significantly reduced intimal thickness compared to the control group (p < 0.01).
- The atorvastatin group showed a lower percentage of α-SMA-positive cells (p < 0.01).
- Atorvastatin inhibited p38 MAPK phosphorylation (p < 0.01) and reduced α-SMA and PCNA levels (p < 0.01), but did not significantly reduce total p38 MAPK (p < 0.05).
Conclusions:
- Atorvastatin effectively inhibits intimal hyperplasia in a rat vein graft model.
- The mechanism involves the inhibition of vascular smooth muscle cell accumulation.
- Atorvastatin exerts its effects by inhibiting the p38 MAPK pathway phosphorylation.
