Abstract 645: 20-HETE and Circulating Endothelial Cells, a Unique Vascular Profile Related to CVD in Morbidly Obese Appalachian Women
Background: A high BMI increases levels of metabolic syndrome biomarkers, including; Leptin in Appalachian women. Vascular dysfunction is persistent in the development of atherosclerosis and determined by the levels of inflammatory markers, circulating endothelial cells (CEC), 20-HETE (a powerful vasoconstrictor) and serum adiponectin levels. We have previously described the presence of a marked increase in CEC in both humans and mice with hypertension, obesity and diabetes. We hypothesize that a subject with high BMI would present with increased levels of CEC and 20-HETE concomitant with a marked reduction in serum adiponectin.
Methods: Serum levels of adiponectin and 20-HETE were measured in female of Appalachian subjects. The effect of 20-HETE on 3T3 adipogenesis was also measured. Mature CEC were isolated from peripheral blood using anti-CD146-coated immunomagnetic Dynabeads™.
Results: Subjects with a BMI between 45 to 72, had an elevated number of CECs (mean 79, range 49-116 cells/ml of peripheral blood) as compared to (mean 29, range 21-46 cells/ml peripheral blood , p<0.05) subjects with BMI of 32-46 and in non-obese subjects with BMI of 17-32, (mean 3, range 2-9). Lipidomic analysis revealed females with high BMI (50-72) displayed a significant increase in the CYP-derived 20-HETE when compared to subject with lower BMI (32-45) (p = 0.005). Treatment of 3T3 cells with 20-HETE decreased serum adiponectin levels and increased TNFα and adipogenesis by 38% and 76%, respectively (p<0.05). These results implicate both 20-HETE and oxidative stress as factors in the development and pathogenesis of BMI-related diseases in individuals with a high BMI.
Conclusions: Increased BMI in Appalachian females is associated with an increase in CEC levels accompanied by an increase in 20-HETE expression and a decrease in adiponectin in peripheral blood. This represents a novel mechanism by which individuals with high BMI and controlled blood pressure remain sensitive to the development of atherogenesis and vascular dysfunction. It is the responsibility of the physician to recognize the medical problems that are endemic to the Appalachian population and to counsel the patient regarding these risks of CVD.
Author Disclosures: M. Getty: None. K. O'Hanlon: None. E. Thompson: None. K. Sodhi: None. E. Maher: None. Z. Khitan: None. N. Puri: None. E. Hochhauser: None. N.G. Abraham: None. J. Shapiro: None.
- © 2014 by American Heart Association, Inc.