Platelets inhibit development of atherosclerosis in atherosclerotic mice

Cell Cycle. 2022 Jun;21(11):1222-1232. doi: 10.1080/15384101.2022.2044703. Epub 2022 Feb 25.

Abstract

Platelets can protect from lipopolysaccharide-induced septic shock by inhibiting inflammation, but it is unknown whether platelets have an anti-atherosclerotic effect. The aim of this study was to investigate the effect of platelet transfusion on atherosclerosis (AS) in a mouse model of AS. Apolipoprotein E deficiency (ApoE-/-) mice were fed with a high-fat diet (HFD) for 8 weeks to establish a mouse model of AS. Mice weekly underwent bi-weekly injection with or without platelets during AS induction (HFD+platelet). Hematoxylin-eosin (H&E), Oil Red O, and Sudan IV stainings were used to assess pathological and morphological changes in the aortic tissue. Lipid levels, and liver and kidney function were examined using an automatic biochemical analyzer. Immune histochemical assays were used to detect the infiltration and distribution of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), IL-6, and monocyte chemotactic protein-1 (MCP-1) in the aortic arch. Western blot and enzyme-linked immunosorbent assay (ELISA) were used to examine the expression levels of TNF-α, IL-1β, IL-6, and MCP-1 in the aorta or the peripheral blood, respectively. Compared with the HFD group, AS pathological lesions from the aortic arch in the HFD+platelet group were significantly smaller and alterations in the lipid metabolism were also less pronounced. Furthermore, TNF-α, IL-1β, IL-6, and MCP-1 levels were all significantly reduced in mice that received platelet injection. Platelets transfusion can effectively ameliorate lipid metabolism, suppress the inflammatory response in the vascular wall, and inhibit the development of AS in mice.

Keywords: Platelets; atherosclerosis; inflammatory factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atherosclerosis* / pathology
  • Blood Platelets / metabolism
  • Disease Models, Animal
  • Interleukin-6
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Tumor Necrosis Factor-alpha* / metabolism

Substances

  • Interleukin-6
  • Tumor Necrosis Factor-alpha

Grants and funding

This study was supported by the Basic Public Welfare Research Project of Zhejiang Province (Grant No. LGJ18H020001), the Major Research and Development Projects for the Zhejiang Science and Technology Agency (Grant No. 2017C03034), and the National Natural Science Foundation of China (Grant No. 81450034).