Validation of Circulating Endothelial Cells and Microparticles in Youth

Identification and validation of early chronic disease biomarkers in children is of paramount
importance especially in the burgeoning arena of pediatric obesity research. Despite the
presence of risk factors, few obese children develop overt CVD early in life. However, the
pathologic process of CVD begins in the first two decades of life, particularly in the
presence of obesity. Because CVD is a cumulative process occurring over time, identifying the
earliest signs in order to intervene sooner may have a large impact on slowing its
progression. The challenge is identifying which obese youth have early vascular problems.
Looking to the vascular endothelium for biomarkers of damage is a reasonable approach because
of its prominent role in the origins of atherosclerosis. Endothelial activation is one of the
earliest detectable signs of the beginnings of CVD and predicts subsequent atherosclerosis
and future cardiovascular events. However, accurately quantifying endothelial health in
children has proven to be a major challenge.

Brachial artery FMD is the most commonly-used method to quantify endothelial health in
children. However, this technique is not widely applicable, even in the research setting,
because it requires specialized equipment and a highly-trained technician. Moreover, results
can be highly variable (especially across sites) due to operator dependence and
intra-individual fluctuations in endothelial function. More direct measures of endothelial
cell biology, such as CEC and EMP, may offer greater precision in characterizing the state of
the endothelium and may be especially useful as risk-prediction biomarkers in youth since
they are hallmarks of advanced endothelial cell distress, thereby identifying the
highest-risk individuals. CEC and EMP have been extensively studied in adults and are
associated with vascular diseases, CVD risk factors, and CVD events. Despite being
well-validated in adults, CEC and EMP have not been formally evaluated as disease biomarkers
in children and adolescents.

Pediatric obesity is an ideal condition in which to validate CEC and EMP as disease
biomarkers since adiposity in childhood is associated with CVD, type 2 diabetes mellitus, and
premature death later in life. In particular, extreme obesity is an especially high-risk
condition associated with significant co-morbidities. Our primary focus in this study will be
the evaluation of CEC and EMP as biomarkers of CVD risk, with a goal of validating CEC and
EMP for use as vascular endpoints in pediatric research studies. We propose to evaluate the
change in levels of CEC and EMP in response to substantial weight loss in adolescents with
extreme obesity undergoing elective, clinically-indicated bariatric surgery.

Specific Aims:

1. Evaluate the effect of substantial weight loss on levels of CEC and EMP in adolescents
with extreme obesity.

We hypothesize that levels of CEC and EMP will be significantly reduced following elective,
clinically-indicated bariatric surgery in adolescents with extreme obesity. The magnitude of
change in CEC and EMP levels will be correlated with the magnitude of weight loss and
improvements in CVD risk factors and endothelial function following bariatric surgery.

We will enroll 32 children and adolescents (ages 8-17) who are scheduled for elective
bariatric surgery. They will be evaluated prior to their surgery, six months after surgery
and twelve months after surgery.

Inclusion Criteria:

- Age 8-17 years old

- Currently scheduled for elective bariatric surgery

Exclusion Criteria: