PMID- 20092994 OWN - NLM STAT- MEDLINE DCOM- 20110228 LR - 20220409 IS - 1873-4847 (Electronic) IS - 0955-2863 (Print) IS - 0955-2863 (Linking) VI - 21 IP - 12 DP - 2010 Dec TI - Abscisic acid ameliorates atherosclerosis by suppressing macrophage and CD4+ T cell recruitment into the aortic wall. PG - 1178-85 LID - 10.1016/j.jnutbio.2009.10.003 [doi] AB - Abscisic acid (ABA) is a natural phytohormone which improves insulin sensitivity and reduces adipose tissue inflammation when supplemented into diets of obese mice. The objective of this study was to investigate the mechanisms by which ABA prevents or ameliorates atherosclerosis. apolipoprotein E-deficient (ApoE(-/-)) mice were fed high-fat diets with or without ABA for 84 days. Systolic blood pressure was assessed on Days 0, 28, 56 and 72. Gene expression, immune cell infiltration and histological lesions were evaluated in the aortic root wall. Human aortic endothelial cells were used to examine the effect of ABA on 3',5'-cyclic adenosine monophosphate (cAMP) and nitric oxide (NO) production in vitro. We report that ABA-treated mice had significantly improved systolic blood pressure and decreased accumulation of F4/80(+)CD11b(+) macrophages and CD4(+) T cells in aortic root walls. At the molecular level, ABA significantly enhanced aortic endothelial nitric oxide synthase (eNOS) and tended to suppress aortic vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) expression and plasma MCP-1 concentrations. ABA also caused a dose-dependent increase in intracellular concentrations of cAMP and NO and up-regulated eNOS mRNA expression in human aortic endothelial cells. This is the first report showing that ABA prevents or ameliorates atherosclerosis-induced hypertension, immune cell recruitment into the aortic root wall and up-regulates aortic eNOS expression in ApoE(-/-) mice. CI - Copyright (c) 2010 Elsevier Inc. All rights reserved. FAU - Guri, Amir J AU - Guri AJ AD - Nutritional Immunology and Molecular Nutrition Laboratory, Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. FAU - Misyak, Sarah A AU - Misyak SA FAU - Hontecillas, Raquel AU - Hontecillas R FAU - Hasty, Alyssa AU - Hasty A FAU - Liu, Dongmin AU - Liu D FAU - Si, Hongwei AU - Si H FAU - Bassaganya-Riera, Josep AU - Bassaganya-Riera J LA - eng GR - R01 AT004308/AT/NCCIH NIH HHS/United States GR - R01 AT004308-02/AT/NCCIH NIH HHS/United States GR - R01 AT004308-03/AT/NCCIH NIH HHS/United States GR - 5R01AT4308/AT/NCCIH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20100125 PL - United States TA - J Nutr Biochem JT - The Journal of nutritional biochemistry JID - 9010081 RN - 72S9A8J5GW (Abscisic Acid) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type III) SB - IM MH - Abscisic Acid/immunology/*pharmacology MH - Animals MH - Aorta/*immunology/metabolism MH - Atherosclerosis/*immunology/prevention & control MH - Blood Pressure/drug effects MH - CD4-Positive T-Lymphocytes/immunology/*metabolism MH - Cells, Cultured MH - Endothelium, Vascular/immunology/metabolism MH - Humans MH - Hypertension/drug therapy MH - Inflammation/immunology/metabolism MH - Macrophages/immunology/*metabolism MH - Mice MH - Mice, Knockout MH - Nitric Oxide Synthase Type III/metabolism PMC - PMC2891372 MID - NIHMS157608 EDAT- 2010/01/23 06:00 MHDA- 2011/03/01 06:00 PMCR- 2011/12/01 CRDT- 2010/01/23 06:00 PHST- 2009/06/30 00:00 [received] PHST- 2009/09/23 00:00 [revised] PHST- 2009/10/05 00:00 [accepted] PHST- 2010/01/23 06:00 [entrez] PHST- 2010/01/23 06:00 [pubmed] PHST- 2011/03/01 06:00 [medline] PHST- 2011/12/01 00:00 [pmc-release] AID - S0955-2863(09)00216-2 [pii] AID - 10.1016/j.jnutbio.2009.10.003 [doi] PST - ppublish SO - J Nutr Biochem. 2010 Dec;21(12):1178-85. doi: 10.1016/j.jnutbio.2009.10.003. Epub 2010 Jan 25.