Relationship of circulating endothelial cells with obesity and cardiometabolic risk factors in children and adolescents

Authors: SOLTERO, ERICA - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC); SOLOVEY, ANNA - UNIVERSITY OF MINNESOTA; HEBBEL, ROBERT - UNIVERSITY OF MINNESOTA; PALZER, ELISE - UNIVERSITY OF MINNESOTA; RYDER, JUSTIN - UNIVERSITY OF MINNESOTA; SHAIBI, GABRIEL - ARIZONA STATE UNIVERSITY; OLSON, MICAH - PHOENIX CHILDREN'S HOSPITAL; FOX, CLAUDIA - UNIVERSITY OF MINNESOTA; RUDSER, KYLE - UNIVERSITY OF MINNESOTA; DENGEL, DONALD - UNIVERSITY OF MINNESOTA; EVANOFF, NICHOLAS - UNIVERSITY OF MINNESOTA; KELLY, AARON - UNIVERSITY OF MINNESOTA

Submitted to: Journal of the American Heart Association
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/22/2020
Publication Date: 12/29/2020
Citation: Soltero, E.G., Solovey, A.N., Hebbel, R.P., Palzer, E.F., Ryder, J.R., Shaibi, G.Q., Olson, M., Fox, C.K., Rudser, K.D., Dengel, D.R., Evanoff, N.G., Kelly, A.S. 2021. Relationship of circulating endothelial cells with obesity and cardiometabolic risk factors in children and adolescents. Journal of the American Heart Association. 10:e018092. https://doi.org/10.1161/JAHA.120.018092.
DOI: https://doi.org/10.1161/JAHA.120.018092

Interpretive Summary: Youth with obesity are at a higher risk for developing cardiovascular diseases. While cardiovascular diseases are not present until adulthood, the early signs of atherosclerosis leading to disease are observable in childhood. To intervene early and prevent downstream disease from occurring, there is a need to identify upstream biomarkers that represent the early stages of atherosclerosis. Based on research in adults, circulating endothelial cells (CECs) are novel, biomarkers that are predictive of cardiovascular diseases, yet few studies have examined CECs in youth. The purpose of this study was to examine the degree to which CEC number and CEC activation is related to obesity and traditional cardiovascular risk factors in youth. Youth were classified into normal weight, obesity, and severe obesity. Blood was drawn to conduct CEC analysis. Cardiovascular risk factors included measures of body composition, blood pressure, glucose, insulin, lipid profile, C-reactive protein, leptin, adiponectin, oxidized low-density lipoprotein cholesterol, carotid artery intima–media thickness, and pulse wave velocity. While CEC number did not differ across weight categories, youth with severe obesity had a higher degree of CEC activation compared to normal weight youth. Higher CEC number was associated with greater body fat percentage and higher blood pressure. Higher degree of CEC activation was associated with greater visceral adipose tissue and non-high density lipoprotein cholesterol. This study demonstrated that methods of CEC quantification are associated with markers of adiposity and cardiovascular risk factors and may potentially reflect accelerated atherosclerosis in youth with sever obesity. CECs show promise as a useful biomarker for identifying youth at high risk of developing cardiovascular disease. However, more research is needed to better understand the role CECs in the development of cardiovascular disease in youth.

Technical Abstract: Circulating endothelial cells (CEC) reflect early changes in endothelial health; however, the degree to which CEC number and activation is related to adiposity and cardiovascular risk factors in youth is not well-described. Youth in this study (N=271; 8-20 years old) were normal weight (BMI% <85th; N=114), obesity (BMI% >=95th to <120% of the 95th; N=63), and severe obesity (BMI% >=120% of the 95th; N=94). CEC enumeration was determined using immunohistochemical examination of buffy coat smears and activated CEC (% Vascular Cell Adhesion Molecule-1 [VCAM-1] expression) was assessed using immunofluorescent staining. Cardiovascular risk factors included measures of body composition, blood pressure, glucose, insulin, lipid profile, C-reactive protein (CRP), leptin, adiponectin, oxidized LDL cholesterol, carotid artery intima-media thickness, and pulse wave velocity. Linear regression models examined associations between CEC number and activation with BMI and cardiovascular risk factors. CEC number did not differ across BMI class (p>0.05). Youth with severe obesity had a higher degree of CEC activation compared normal weight youth (8.3% [95% CI:1.1, 15.6]; p=0.024). Higher CEC number was associated with greater body fat percentage (0.02 per percentage [0.00, 0.03]; p=0.020) and systolic blood pressure percentile (0.01 per percentage [0.00, 0.01]; p=0.035). Higher degree of CEC activation was associated with greater visceral adipose tissue (5.7% per kg [0.4, 10.9]; p=0.034) and non-HDL cholesterol (0.11% per mg/dL [0.01,0.21]; p=0.039). Methods of CEC quantification are associated with adiposity and cardiometabolic risk factors and may potentially reflect accelerated atherosclerosis as early as childhood.