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Abscisic acid ameliorates atherosclerosis by suppressing macrophage and CD4+ T cell recruitment into the aortic wall.

Abstract
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.
AuthorsAmir J Guri, Sarah A Misyak, Raquel Hontecillas, Alyssa Hasty, Dongmin Liu, Hongwei Si, Josep Bassaganya-Riera
JournalThe Journal of nutritional biochemistry (J Nutr Biochem) Vol. 21 Issue 12 Pg. 1178-85 (Dec 2010) ISSN: 1873-4847 [Electronic] United States
PMID20092994 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2010 Elsevier Inc. All rights reserved.
Chemical References
  • Abscisic Acid
  • Nitric Oxide Synthase Type III
Topics
  • Abscisic Acid (immunology, pharmacology)
  • Animals
  • Aorta (immunology, metabolism)
  • Atherosclerosis (immunology, prevention & control)
  • Blood Pressure (drug effects)
  • CD4-Positive T-Lymphocytes (immunology, metabolism)
  • Cells, Cultured
  • Endothelium, Vascular (immunology, metabolism)
  • Humans
  • Hypertension (drug therapy)
  • Inflammation (immunology, metabolism)
  • Macrophages (immunology, metabolism)
  • Mice
  • Mice, Knockout
  • Nitric Oxide Synthase Type III (metabolism)

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