title: Hyperglycemia-induced ascorbic acid deficiency promotes endothelial dysfunction and the development of atherosclerosis.
abstract: Dehydroascorbic acid, the oxidized form of vitamin C, is transported into mammalian cells via facilitative glucose transporters and hyperglycemia inhibits this process by competitive inhibition. This inhibited transport may promote oxidative stress and contribute to the increase in atherosclerotic cardiovascular disease observed in patients with diabetes mellitus. This review explores the importance of this proposed mechanism in light of current research. For example, recent reports suggest that administration of antioxidants, such as vitamin C, may slow atherogenesis by improving endothelium-dependent vasodilation in individuals with abnormal glucose and lipid metabolism, perhaps by preventing the oxidation of nitric oxide, an important regulator of vasomotor tone. Endothelial dysfunction plays a key role in the development of atherosclerosis and endothelial cells may be particularly affected by hyperglycemia-induced ascorbic acid deficiency as they line the interior of blood vessels. In addition, we discuss evidence of several other mechanisms by which vitamin C status may affect the development of atherosclerotic cardiovascular disease, particularly its inverse relationship to multiple cardiovascular disease risk factors and indicators. Given these factors, vitamin C administration is recommended during periods of both acute and chronic hyperglycemia to help preserve endothelial function.
authors.affiliation: Department of Pathology, Stanford University Medical Center, Stanford, CA 94305-5324, USA. kendall.price@stanford.edu
authors.forename: K D
authors.initials: KD
authors.lastname: Price
authors.forename: C S
authors.initials: CS
authors.lastname: Price
authors.forename: R D
authors.initials: RD
authors.lastname: Reynolds
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D001205:Ascorbic Acid / Q000502:physiology* / Q000627:therapeutic use; D001206:Ascorbic Acid Deficiency / Q000209:etiology / Q000503:physiopathology*; D003094:Collagen / Q000378:metabolism; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D006943:Hyperglycemia / Q000150:complications*
chemical_list: D000975:Antioxidants; D003094:Collagen; D001205:Ascorbic Acid