Open Access

Inhibition of the mevalonate pathway improves myocardial fibrosis

  • Authors:
    • Huifeng Xu
    • Yi Shen
    • Chenyu Liang
    • Haifeng Wang
    • Junling Huang
    • Pengcheng Xue
    • Ming Luo
  • View Affiliations

  • Published online on: January 18, 2021     https://doi.org/10.3892/etm.2021.9655
  • Article Number: 224
  • Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The mevalonate (MVA) pathway serves an important role in ventricular remodeling. Targeting the MVA pathway has protective effects against myocardial fibrosis. The present study aimed to investigate the mechanism behind these effects. Primary cultured cardiac fibroblasts from C57BL/6 mice were treated in vitro in 5 groups: i) negative control; ii) angiotensin II (Ang II) model (1x10‑5 mol/l); iii) Ang II + rosuvastatin (ROS); iv) Ang II + alendronate (ALE); and v) Ang II + fasudil (FAS). Collagen and crystal violet staining were used to assess morphological changes in cardiac fibroblasts. Reverse transcription quantitative PCR and western blotting were used to analyze the expression of key signaling molecules involved in the MVA pathway. Collagen staining in the ALE, FAS, and ROS groups was weak compared with the Ang II group, while the rate of cell proliferation in the ROS, ALE, and FAS groups was slower compared with that in the Ang II group. In addition, the expression of key signaling molecules in the MVA pathway, including transforming growth factor‑β1 (TGF‑β1), heat shock protein 47 (HSP47), collagen type I α1 (COL1A1), vascular endothelial growth factor 2 (VEGF2) and fibroblast growth factor 2 (FGF2), was decreased in the FAS and ROS groups compared with the Ang II model. Compared with the Ang II group, 3‑Hydroxy‑3‑Methylglutaryl‑CoA reductase (HMGCR) gene expression was significantly lowered in the drug intervention groups, whereas farnesyl pyrophosphate synthase (FDPS) expression was downregulated in the ALE group, but elevated in the FAS and ROS groups. Compared with that in the Ang II group, ras homolog family member A (RhoA) expression was downregulated in the FAS and ROS groups, whilst mevalonate kinase expression was reduced in the ROS group. Protein expression of TGF‑β1, COL1A1 and HSP47 were decreased following intervention with each of the three drugs compared with the Ang II group. Overall, rosuvastatin, aledronate and fasudil decreased the proliferation of myocardial fibroblasts and inhibited collagen synthesis. Rosuvastatin had the strongest protective effects against myocardial fibrosis compared with the other drugs tested, suggesting this to be a potential agent for the clinical treatment of cardiovascular disease.
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March-2021
Volume 21 Issue 3

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Copy and paste a formatted citation
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Spandidos Publications style
Xu H, Shen Y, Liang C, Wang H, Huang J, Xue P and Luo M: Inhibition of the mevalonate pathway improves myocardial fibrosis. Exp Ther Med 21: 224, 2021
APA
Xu, H., Shen, Y., Liang, C., Wang, H., Huang, J., Xue, P., & Luo, M. (2021). Inhibition of the mevalonate pathway improves myocardial fibrosis. Experimental and Therapeutic Medicine, 21, 224. https://doi.org/10.3892/etm.2021.9655
MLA
Xu, H., Shen, Y., Liang, C., Wang, H., Huang, J., Xue, P., Luo, M."Inhibition of the mevalonate pathway improves myocardial fibrosis". Experimental and Therapeutic Medicine 21.3 (2021): 224.
Chicago
Xu, H., Shen, Y., Liang, C., Wang, H., Huang, J., Xue, P., Luo, M."Inhibition of the mevalonate pathway improves myocardial fibrosis". Experimental and Therapeutic Medicine 21, no. 3 (2021): 224. https://doi.org/10.3892/etm.2021.9655