title: Hyperglycemia and loss of ovarian hormones mediate atheroma formation through endothelial layer disruption and increased permeability.
abstract: The overall goal of this project was to examine the interactions of hyperglycemia and loss of ovarian hormones on the artery wall in a type I diabetic mouse model. Intact or ovariectomized (OVX) female BALB/C mice were fed a high-cholesterol diet. Half the animals were treated with steptozotocin to induce insulin-deficient diabetes mellitus, generating four treatment groups: control, intact; control, ovariectomized; diabetic, intact; diabetic, ovariectomized (DOVX). We examined arterial structure and function and found that 1) diabetes and ovariectomy additively increased endothelial layer permeability, 2) arterial stiffening was increased in DOVX, 3) DOVX synergistically increased atheroma formation, and 4) ultrastructural evaluation revealed that the basal lamina was often multilayered and formed convoluted aggregates separating endothelium from the internal elastic lamina in diabetic, but not control arteries or arteries from OVX mice. Endothelium overlying these regions formed thin cytoplasmic extensions between these aggregates and was often separated from the basal lamina by electron lucent spaces. Our studies showed that diabetes and loss of ovarian function have additive and synergistic effects to worsen arterial pathophysiology by disrupting the arterial endothelial layer with increased permeability and increased atheroma formation.
authors.affiliation: School of Medicine, University of California, Davis, CA 95616, USA.
authors.forename: Jeana
authors.initials: J
authors.lastname: Benton
authors.forename: Andrew
authors.initials: A
authors.lastname: Powers
authors.forename: Larissa
authors.initials: L
authors.lastname: Eiselein
authors.forename: Richard
authors.initials: R
authors.lastname: Fitch
authors.forename: Dennis
authors.initials: D
authors.lastname: Wilson
authors.forename: Amparo C
authors.initials: AC
authors.lastname: Villablanca
authors.forename: John C
authors.initials: JC
authors.lastname: Rutledge
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000473:pathology*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D002199:Capillary Permeability / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000473:pathology* / Q000648:ultrastructure; D005260:Female; D005456:Fluorescent Dyes; D006943:Hyperglycemia / Q000473:pathology*; D008077:Lipoproteins, LDL / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D009929:Organ Size / Q000502:physiology; D010052:Ovariectomy; D012039:Regional Blood Flow / Q000502:physiology; D014599:Uterus / Q000502:physiology
chemical_list: D001786:Blood Glucose; D005456:Fluorescent Dyes; D008077:Lipoproteins, LDL