title: Curcumin ameliorates arterial dysfunction and oxidative stress with aging.
abstract: We tested the hypothesis that curcumin supplementation would reverse arterial dysfunction and vascular oxidative stress with aging. Young (Y, 4-6 months) and old (O, 26-28 months) male C57BL6/N mice were given normal or curcumin supplemented (0.2%) chow for 4 weeks (n=5-10/group/measure). Large elastic artery stiffness, assessed by aortic pulse wave velocity (aPWV), was greater in O (448±15 vs. 349±15 cm/s) and associated with greater collagen I and advanced glycation end-products and less elastin (all P<0.05). In O, curcumin restored aPWV (386±15 cm/s), collagen I and AGEs (AGEs) to levels not different vs. Y. Ex vivo carotid artery acetylcholine (ACh)-induced endothelial-dependent dilation (EDD, 79±3 vs. 94±2%), nitric oxide (NO) bioavailability and protein expression of endothelial NO synthase (eNOS) were lower in O (all P<0.05). In O, curcumin restored NO-mediated EDD (92±2%) to levels of Y. Acute ex vivo administration of the superoxide dismutase (SOD) mimetic TEMPOL normalized EDD in O control mice (93±3%), but had no effect in Y control or O curcumin treated animals. O had greater arterial nitrotyrosine abundance, superoxide production and NADPH oxidase p67 subunit expression, and lower manganese SOD (all P<0.05), all of which were reversed with curcumin. Curcumin had no effects on Y. Curcumin supplementation ameliorates age-associated large elastic artery stiffening, NO-mediated vascular endothelial dysfunction, oxidative stress and increases in collagen and AGEs in mice. Curcumin may be a novel therapy for treating arterial aging in humans.
authors.affiliation: Department of Integrative Physiology, University of Colorado, Boulder, CO 80309, USA. bradley.fleenor@uky.edu
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Fleenor
authors.forename: Amy L
authors.initials: AL
authors.lastname: Sindler
authors.forename: Natasha K
authors.initials: NK
authors.lastname: Marvi
authors.forename: Kate L
authors.initials: KL
authors.lastname: Howell
authors.forename: Melanie L
authors.initials: ML
authors.lastname: Zigler
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Yoshizawa
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Seals
mesh_terms: D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002339:Carotid Arteries / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D024042:Collagen Type I / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004549:Elastin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D017127:Glycation End Products, Advanced / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010750:Phosphoproteins / Q000378:metabolism; D063177:Pulse Wave Analysis; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D059289:Vascular Stiffness / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D024042:Collagen Type I; D017127:Glycation End Products, Advanced; D010750:Phosphoproteins; D014665:Vasodilator Agents; C079789:neutrophil cytosol factor 67K; D013481:Superoxides; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D004549:Elastin; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D013482:Superoxide Dismutase; D003474:Curcumin