Inhibition of Lipoprotein-Associated Phospholipase A2 Ameliorates Inflammation and Decreases Atherosclerotic Plaque Formation in ApoE-Deficient Mice
2011

Inhibition of Lp-PLA2 Reduces Inflammation and Atherosclerosis in Mice

Sample size: 50 publication Evidence: moderate

Author Information

Author(s): Wang Wen-yi, Zhang Jie, Wu Wen-yu, Li Jie, Ma Yan-ling, Chen Wei-hai, Yan Hong, Wang Kai, Xu Wen-wei, Shen Jian-hua, Wang Yi-ping

Primary Institution: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China

Hypothesis

Does the specific Lp-PLA2 inhibitor darapladib affect atherosclerosis development in ApoE-deficient mice?

Conclusion

Inhibition of Lp-PLA2 by darapladib reduces inflammation and plaque formation in ApoE-deficient mice.

Supporting Evidence

  • Serum Lp-PLA2 activity was inhibited by more than 60% after treatment with darapladib.
  • Levels of inflammatory markers hs-CRP and IL-6 were significantly reduced in the darapladib group.
  • The plaque area in the darapladib group was significantly smaller compared to the control group.
  • Macrophage content in atherosclerotic lesions was lower in the darapladib group.
  • Collagen content in lesions was higher in the darapladib group, indicating more stable plaques.
  • Expression of inflammatory genes MCP-1, VCAM-1, and TNF-α was lower in the darapladib group.

Takeaway

This study shows that a drug called darapladib can help reduce heart disease by lowering inflammation and plaque buildup in mice.

Methodology

ApoE-deficient mice were fed a high-fat diet and treated with darapladib or saline for 6 weeks, followed by analysis of serum and aortic samples.

Limitations

The detailed mechanisms of how darapladib affects atherosclerosis are not fully understood.

Participant Demographics

Male homozygous ApoE-deficient mice (C57/Bl6 genetic background)

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0023425

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