title: Hyperglycemia-induced latent scurvy and atherosclerosis: the scorbutic-metaplasia hypothesis.
abstract: Latent scurvy is characterized by a reversible atherosclerosis that closely resembles the clinical form of this disease. Acute scurvy is characterized by microvascular complications such as widespread capillary hemorrhaging. Vitamin C (ascorbate) is required for the synthesis of collagen, the protein most critical in the maintenance of vascular integrity. We suggest that in latent scurvy, large blood vessels use modified LDL--in particular lipoprotein(a)--in addition to collagen to maintain macrovascular integrity. By this mechanism, collagen is spared for the maintenance of capillaries, the sites of gas and nutrient exchange. The foam-cell phenotype of atherosclerosis is identified as a mesenchymal genetic program, regulated by the availability of ascorbate. When vitamin C is limited, foam cells develop and induce oxidative modification of LDL, thereby stabilizing large blood vessels via the deposition of LDL. The structural similarity between vitamin C and glucose suggests that hyperglycemia will inhibit cellular uptake of ascorbate, inducing local vitamin C deficiency.
authors.affiliation: University of Illinois at Chicago, College of Medicine 60612, USA.
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; D001161:Arteriosclerosis / Q000209:etiology* / Q000378:metabolism; D001205:Ascorbic Acid / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000378:metabolism; D005487:Foam Cells / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000150:complications* / Q000378:metabolism; D017270:Lipoprotein(a) / Q000378:metabolism; D008679:Metaplasia; D008954:Models, Biological; D012614:Scurvy / Q000209:etiology* / Q000378:metabolism
chemical_list: D017270:Lipoprotein(a); D003094:Collagen; D001205:Ascorbic Acid