Investigation of the Molecular Mechanisms Underlying the Antiatherogenic Actions of Kaempferol in Human THP-1 Macrophages

Int J Mol Sci. 2022 Jul 5;23(13):7461. doi: 10.3390/ijms23137461.

Abstract

Cardiovascular disease (CVD) is causing high mortality worldwide (World Health Organization-WHO, 2015). Atherosclerosis, the hardening and narrowing of arteries caused by the accumulation of fatty acids and lipids (cholesterol plaques), is a main reason of stroke, myocardial infarction, and angina. Present therapies for cardiovascular disease basically use statins such as β-Hydroxy β-methylglutaryl-CoA, with <70% efficacy and multiple side effects. An in vitro investigation was conducted to evaluate the impact of kaempferol, a natural medication, in an atherosclerotic cell model. We used cytotoxicity assays, Boyden chamber invasion assays, and quantitative PCR. Affymetrix microarrays were used to profile the entire transcriptome of kaempferol-treated cell lines, and Partek Genomic Suite was used to interpret the results. Kaempferol was not cytotoxic to THP-1 macrophages. In comparison to the control, kaempferol reduced monocyte migration mediated by monocyte chemotactic protein 1 (MCP-1) by 80%. The qPCR results showed a 73.7-fold reduction in MCP-1 and a 2.5-fold reduction in intercellular adhesion molecule 1 (ICAM-1) expression in kaempferol-treated cells. In interferon gamma (IFN-γ) without kaempferol and IFN-γ with kaempferol treated cells, we found 295 and 168 differentially expressed genes (DEGs), respectively. According to DEG pathway analysis, kaempferol exhibits anti-atherosclerosis and anti-inflammatory characteristics. Kaempferol is an effective and safe therapy for atherosclerosis.

Keywords: Affymetrix microarrays; ICAM-1; IFN-γ; MCP-1; cardiovascular disease atherosclerosis; human THP-1 macrophages; kaempferol.

MeSH terms

  • Atherosclerosis* / drug therapy
  • Atherosclerosis* / metabolism
  • Cardiovascular Diseases* / metabolism
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Cholesterol / metabolism
  • Humans
  • Interferon-gamma / metabolism
  • Macrophages / metabolism
  • Monocytes / metabolism

Substances

  • Chemokine CCL2
  • Interferon-gamma
  • Cholesterol

Grants and funding

This research was not funded.