PMID- 35806463 OWN - NLM STAT- MEDLINE DCOM- 20220712 LR - 20230308 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 23 IP - 13 DP - 2022 Jul 5 TI - Investigation of the Molecular Mechanisms Underlying the Antiatherogenic Actions of Kaempferol in Human THP-1 Macrophages. LID - 10.3390/ijms23137461 [doi] LID - 7461 AB - 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 beta-Hydroxy beta-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-gamma) without kaempferol and IFN-gamma 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. FAU - Huwait, Etimad AU - Huwait E AUID- ORCID: 0000-0002-4657-6668 AD - Biochemistry Department, Faculty of Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia. AD - Cell Culture Unit and Experimental Biochemistry Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah 21589, Saudi Arabia. FAU - Ayoub, Maha AU - Ayoub M AUID- ORCID: 0000-0002-1491-7851 AD - Biochemistry Department, Faculty of Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia. AD - Cell Culture Unit and Experimental Biochemistry Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah 21589, Saudi Arabia. FAU - Karim, Sajjad AU - Karim S AUID- ORCID: 0000-0003-0907-2097 AD - Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia. AD - Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia. LA - eng PT - Journal Article DEP - 20220705 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Chemokine CCL2) RN - 82115-62-6 (Interferon-gamma) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - *Atherosclerosis/drug therapy/metabolism MH - *Cardiovascular Diseases/metabolism MH - Chemokine CCL2/genetics/metabolism MH - Cholesterol/metabolism MH - Humans MH - Interferon-gamma/metabolism MH - Macrophages/metabolism MH - Monocytes/metabolism PMC - PMC9267302 OTO - NOTNLM OT - Affymetrix microarrays OT - ICAM-1 OT - IFN-gamma OT - MCP-1 OT - cardiovascular disease atherosclerosis OT - human THP-1 macrophages OT - kaempferol COIS- The authors declare that they have no competing interests. EDAT- 2022/07/10 06:00 MHDA- 2022/07/14 06:00 PMCR- 2022/07/05 CRDT- 2022/07/09 01:13 PHST- 2022/06/14 00:00 [received] PHST- 2022/06/29 00:00 [revised] PHST- 2022/06/30 00:00 [accepted] PHST- 2022/07/09 01:13 [entrez] PHST- 2022/07/10 06:00 [pubmed] PHST- 2022/07/14 06:00 [medline] PHST- 2022/07/05 00:00 [pmc-release] AID - ijms23137461 [pii] AID - ijms-23-07461 [pii] AID - 10.3390/ijms23137461 [doi] PST - epublish SO - Int J Mol Sci. 2022 Jul 5;23(13):7461. doi: 10.3390/ijms23137461.