Hyperglycemia and loss of ovarian hormones mediate atheroma formation through endothelial layer disruption and increased permeability

Jeana Benton, Andrew Powers, Larissa Eiselein, Richard Fitch, Dennis W Wilson, Amparo C Villablanca, John C Rutledge

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 highcholesterol 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume292
Issue number2
DOIs
StatePublished - Feb 2007

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Atherosclerotic Plaques
Hyperglycemia
Permeability
Arteries
Hormones
Basement Membrane
Endothelium
Inbred BALB C Mouse
Ovariectomy
Diabetes Mellitus
Electrons
Insulin
Diet
Control Groups

Keywords

  • Atherosclerosis
  • Diabetes
  • Pathophysiology
  • Postmenopause
  • Vascular

ASJC Scopus subject areas

  • Physiology

Cite this

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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 highcholesterol 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.",
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AU - Wilson, Dennis W

AU - Villablanca, Amparo C

AU - Rutledge, John C

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