title: Chlorogenic acid improves ex vivo vessel function and protects endothelial cells against HOCl-induced oxidative damage, via increased production of nitric oxide and induction of Hmox-1.
abstract: Dietary polyphenols are potential contributors toward improved cardiovascular health. Coffee is one of the richest sources of dietary polyphenols in a coffee-drinking population, the most abundant form being chlorogenic acid (CGA). Endothelial dysfunction is an early and major risk factor for cardiovascular disease. Nitric oxide (NO) is a key factor in regulation of endothelial function. Heme oxygenase-1 (Hmox-1), an inducible isoform of heme oxygenase that is produced in response to stressors such as oxidative stress, may also play a role in vascular protection. The aim of this study was to investigate the effect of CGA on endothelial function with oxidant-induced damage in isolated aortic rings from C57BL mice. We further examine the mechanism by investigating cell viability, activation of eNOS and induction of Hmox-1 in human aortic endothelial cells (HAECs). We found that pretreatment of isolated aortic rings with 10-μM CGA-protected vessels against HOCl-induced endothelial dysfunction (P<0.05). Pretreatment of cultured HAECs with 10-μM CGA increased endothelial cell viability following exposure to HOCl (P<0.05). Moreover, CGA increased NO production in HAECs in a dose-dependent manner, peaking at 6 h (P<0.05). CGA at 5 μM and 10 μM increased eNOS dimerization at 6 h and induced Hmox-1 protein expression at 6 h and 24 h in HAECs. These results are consistent with the cardiovascular protective effects of coffee polyphenols and demonstrate that CGA can protect vessels and cultured endothelial cells against oxidant-induced damage. The mechanism behind the beneficial effect of CGA appears to be in part via increased production of NO and induction of Hmox-1.
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Level 4, Medical Research Foundation Building, Rear 50 Murray St., Perth, WA, 6000, Australia.
authors.forename: Rujia
authors.initials: R
authors.lastname: Jiang
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Level 4, Medical Research Foundation Building, Rear 50 Murray St., Perth, WA, 6000, Australia.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Hodgson
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Level 4, Medical Research Foundation Building, Rear 50 Murray St., Perth, WA, 6000, Australia.
authors.forename: Emilie
authors.initials: E
authors.lastname: Mas
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Level 4, Medical Research Foundation Building, Rear 50 Murray St., Perth, WA, 6000, Australia. Electronic address: kevin.croft@uwa.edu.au.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Croft
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Level 4, Medical Research Foundation Building, Rear 50 Murray St., Perth, WA, 6000, Australia; School of Biomedical Science & Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia.
authors.forename: Natalie C
authors.initials: NC
authors.lastname: Ward
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002478:Cells, Cultured; D002726:Chlorogenic Acid / Q000378:metabolism / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006997:Hypochlorous Acid / Q000633:toxicity*; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D002726:Chlorogenic Acid; D006997:Hypochlorous Acid
keywords: Chlorogenic acid; Endothelial function; Heme oxygenase-1; Nitric oxide; Oxidative stress; Polyphenols