PMID- 26696442 OWN - NLM STAT- MEDLINE DCOM- 20170106 LR - 20170107 IS - 1533-4023 (Electronic) IS - 0160-2446 (Linking) VI - 67 IP - 4 DP - 2016 Apr TI - Effects of Ethyl Pyruvate in Preventing the Development of Diet-induced Atherosclerosis by Blocking the HMGB1 Expression in ApoE-Deficient Mice. PG - 299-304 LID - 10.1097/FJC.0000000000000353 [doi] AB - Ethyl pyruvate (EP) is a lipid derivative of pyruvate and known as an anti-inflammatory agent effective to inhibit many diseases in experimental models. To test the hypothesis that Ethyl pyruvate might prevent atherosclerosis development by blocking the high-mobility group box-1 (HMGB1) expression, 8-week-old ApoE-deficient (ApoE-/-) mice were fed a high-fat diet and treated with EP (50 mg/Kg) or Physiological saline for 12 weeks. THP-1 cells were then differentiated into macrophages by treated with Phorbol-12-myristate-13-acetate (PMA, 100 ng/mL) and incubated with oxidized low-density lipoprotein (oxLDL) only or added with EP (5 mM) for 24 hour. In ApoE-/- mice, EP markedly reduced aortic sinus atherosclerosis lesions with no influence to serum lipid levels. Inhibited HMGB1 expression, decreased macrophages content and reduced Toll-like-receptor2 (TLR2), TLR4, monocyte chemotactic protein 1 (MCP-1) and Tumor Necrosis Factor alpha (TNF-alpha) mRNA levels were also observed at the same time. In vitro, EP decreased oxLDL uptake in macrophages and inhibited HMGB1 expression induced by oxLDL. In conclusion, our study indicated that EP was an effective agent against the development of diet-induced atherosclerosis in ApoE-deficient mice by way of blocking the HMGB1 expression. FAU - Xiao, Hunan AU - Xiao H AD - Department of Geriatric Cardiology, Chinese People's Liberation Army General Hospital, Beijing, China. FAU - Liu, Hongbin AU - Liu H FAU - Hou, Congcong AU - Hou C FAU - Liu, Yang AU - Liu Y FAU - Yu, Qian AU - Yu Q LA - eng PT - Journal Article PL - United States TA - J Cardiovasc Pharmacol JT - Journal of cardiovascular pharmacology JID - 7902492 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Apolipoproteins E) RN - 0 (HMGB1 Protein) RN - 0 (Lipids) RN - 0 (Lipoproteins, LDL) RN - 0 (Pyruvates) RN - 0 (oxidized low density lipoprotein) RN - 03O98E01OB (ethyl pyruvate) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - Animals MH - Anti-Inflammatory Agents/pharmacology MH - Apolipoproteins E/*genetics MH - Atherosclerosis/etiology/*prevention & control MH - Diet, High-Fat MH - Gene Expression Regulation/drug effects MH - HMGB1 Protein/*genetics MH - Lipids/blood MH - Lipoproteins, LDL/administration & dosage/metabolism MH - Macrophages/metabolism MH - Male MH - Mice MH - Mice, Knockout MH - Pyruvates/*pharmacology MH - Tetradecanoylphorbol Acetate/pharmacology EDAT- 2015/12/24 06:00 MHDA- 2017/01/07 06:00 CRDT- 2015/12/24 06:00 PHST- 2015/12/24 06:00 [entrez] PHST- 2015/12/24 06:00 [pubmed] PHST- 2017/01/07 06:00 [medline] AID - 10.1097/FJC.0000000000000353 [doi] PST - ppublish SO - J Cardiovasc Pharmacol. 2016 Apr;67(4):299-304. doi: 10.1097/FJC.0000000000000353.