Placental Structure and Biological Aspects of Fetal Membranes Cultured in vitro

Abstract

Objectives: The relative-risk of atherosclerotic cardiovascular disease (ACVD) is elevated in childhood cancer survivors (CCS) secondary to cancer-therapies causing vascular endothelial impairment. Novel biomarkers of endothelial inflammation analyzed from the peripheral blood (PB) may aid in identifying CCS at risk for future ACVD. These biomarkers include the bona fide endothelial progenitor cells, termed endothelial colony-forming cells (ECFCs), that are essential for vascular homeostasis and repair, as well as, apoptotic mature circulating endothelial cells (CECs). The purpose of this study was to analyze ECFCs and CECs from the PB of CCS using a novel multi-parametric flow-cytometry protocol. Methods: In this cross-sectional study we compared Cardiovascular Risk Factors (CRFs), quality of life measures, diet, physical-activity (PA), brachial-artery flow-mediated dilatation (FMD), a measure of endothelial function, and ECFCs and CECs between CCS and age and body-mass index matched healthy controls (HC). In addition, we investigated the effect of cancer therapies on FMD, ECFCs, and CECs and the associations between these measures and CRFs, PA and diet. Results: We enrolled 24 CCS, 17 with a prior diagnosis of leukemia. The CCS had significantly lower physical functioning and PA, worse diet, higher fatigue and lower high-density cholesterol (HDL-C) compared to HC (all p < 0.05). There was no difference in FMD, ECFCs and CECs between CCS and HC. Within the CCS cohort, those with any radiotherapy (RT) had significantly lower ECFCs and CECs (both p=0.02). In addition, significant positive correlations included, HDL-C with FMD and PA with ECFCs while significant negative correlations included systolic blood-pressure with ECFCs (all p < 0.05). Conclusions: This study involved CCS showing that ECFCs are affected by cancer-therapies, such as RT, further worsened by CRFs such as hypertension and life-styles with inadequate PA. Altering these modifiable risk-factors can potentially improve vascular health to prevent future ACVD.