Abstract 14450: Repetitive High Resolution Ultrasound Demonstrates that Vitamin E Inhibits Atherosclerotic Plaque Growth in Haptoglobin 2-2 Diabetic Mice in vivo
Introduction. Nine independent longitudinal studies have demonstrated that individuals with the Hp 2-2 genotype and Diabetes Mellitus (DM), who constitute approximately 40% of all individuals with DM, have a 2-3 fold increased incidence of atherosclerotic CVD and its sequalae as compared to DM individuals without the Hp 2-2 genotype. Three studies have demonstrated that vitamin E significantly reduces incident CVD specifically in Hp 2-2 DM individuals. The ability to study the interaction between the Hp genotype and vitamin E in vivo on diabetic CVD has been hampered by an inability to assess this interaction serially over time in the same subject.
Objective. We sought to develop an animal model for the interaction between the Hp genotype and vitamin E on diabetic atherosclerosis that would allow for the repeated assessment of plaque growth over time in the same animal.
Methods. The Hp 2 allele, present only in man, is defined by the presence of a 1.7kb in-frame duplication of exons 3 and 4 of the Hp 1 allele. We engineered a murine Hp 2 allele and introduced it into the murine Hp locus by homologous recombination. We backcrossed Hp 2 and wild type (Hp 1) mice into an ApoE -/- background. Diabetes was induced by streptozotocin injection at 3 months of age. Vitamin E or placebo was initiated at 4 months of age. Plaque parameters were assessed using high resolution ultrasound (Vevo-2100, Visualsonics) in the brachiocephalic artery at multiple time points in the same animal.
Results. Atherosclerotic plaques were approximately 80% larger in age and gender matched Hp 2-2 ApoE-/- mice as compared to Hp 1-1 ApoE-/-mice (p<0.05) in the presence or absence of DM. Vitamin E completely arrested plaque growth in Hp 2-2 DM mice (p<0.0001 for rate of plaque growth compared to Hp 2-2 DM mice without vitamin E).
Conclusion. Accelerated atherosclerosis can be demonstrated in Hp 2-2 DM mice in vivo and can be inhibited by vitamin E, thereby providing further evidence for a direct interaction between Hp genotype and Vitamin E on diabetic CVD.
- © 2012 by American Heart Association, Inc.