title: Established atherosclerosis might be a prerequisite for chicory and its constituent protocatechuic acid to promote endothelium-dependent vasodilation in mice.
abstract: Chicory (Cichorium intybus L. var. foliosum, Belgian endive), a typical Mediterranean vegetable, and its constituent protocatechuic acid (PCA) can inhibit established atherosclerosis progression. We thus investigated whether chicory can improve vascular relaxation, a critical pathway for combating atherosclerosis, and whether PCA is a contributor to a chicory-induced effect.
  
  
  
  Apolipoprotein E-deficient (ApoE-/-) mice with established atherosclerosis and C57BL/6J mice without atherosclerosis were fed an AIN-93G diet, or AIN-93G plus 0.5% freeze-dried chicory or 0.003% PCA for 1 wk. In ApoE-/-mice, both chicory and PCA consumption increased endothelium-dependent vasodilation and endothelial nitric oxide synthase (eNOS) activity independent of eNOS and phospho-eNOS Ser1177 and Thr495 protein expression. Chicory- or PCA-induced eNOS activities were associated with increased vascular tetrahydrobiopterin (BH4) levels that result from reduced BH4oxidation partially through preventing eNOS uncoupling. In C57BL/6J mice, neither chicory nor PCA consumption affected endothelium-dependent vasodilation and eNOS activity. Notably, in vitro studies showed that PCA increases eNOS activity in mouse aortic endothelial cells in co-culture with macrophage foam cells, but not in aortic endothelial cells alone.
  
  
  
  Chicory improves eNOS-mediated endothelium-dependent vasodilation by increasing BH4levels in mice with established atherosclerosis, which might be partially ascribed to its constituent PCA.
authors.affiliation: Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, P. R. China.
authors.forename: Chaoqun
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, P. R. China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, P. R. China.
authors.forename: Weiqun
authors.initials: W
authors.lastname: Lin
authors.affiliation: Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, P. R. China.|Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, P. R. China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Ling
authors.affiliation: Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, P. R. China. wdliang@mail.sysu.edu.cn.|Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, P. R. China. wdliang@mail.sysu.edu.cn.
authors.forename: Dongliang
authors.initials: D
authors.lastname: Wang
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology; D001708:Biopterins / Q000031:analogs & derivatives / Q000378:metabolism; D018651:Cichorium intybus / Q000737:chemistry*; D002784:Cholesterol / Q000378:metabolism; D018920:Coculture Techniques; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D062385:Hydroxybenzoates / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D001057:Apolipoproteins E; D062385:Hydroxybenzoates; D001708:Biopterins; C009091:protocatechuic acid; D002784:Cholesterol; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; C003402:sapropterin; D006152:Cyclic GMP
keywords: Atherosclerosis; Chicory; Endothelial function; Macrophage; Protocatechuic acid