Endothelial colony-forming cells as a platform for early cardiovascular risk assessment

Thesis

The human endothelial colony-forming cells (ECFCs), a subpopulation of endothelial progenitor cells (EPCs), offer a potential platform for cellular assessment due to their remarkable angiogenic expansion, regenerative, and self-renewable potentials in vitro. This thesis investigated how ECFC function and proteome profiles are altered in young adults with elevated cardiovascular disease (CVD) risk factors, including increased blood pressure (BP). It also demonstrated the effect of an exercise intervention on ECFC function and the potential to use ECFC to predict response to exercise intervention.

The main investigations of this thesis were based on a cohort of young adult participants aged 18 to 35 years, recruited through the Trial of Exercise to Prevent HypeRtension in young Adults (TEPHRA). Detailed clinical measurements, including BP measurements, retinal micro-vascular imaging, pulse wave velocity, blood biochemistry and lipid profiles, as well as ECFC culture and cellular assessments, were performed at baseline pre-exercise intervention. Measurements were repeated following a 16-week exercise intervention training period in a subgroup of participants. Our data presented a distinct proteomic signature with altered angiogenic mechanisms in dysfunctional ECFCs. An increase in CVD risks, including higher BP, body mass index and impaired lipid profile, were associated with a reduction in expansion and vasculogenic capacity in dysfunctional ECFCs. Further analysis revealed that the young adults with elevated BP had significantly reduced ECFC functionality and presented a potentially adverse retinal micro-vascular structure and greater macro-vascular resistance. Although no significant changes were observed in the ECFCs after exercise intervention, we demonstrated that baseline ECFC functional characteristics might positively affect aerobic training response. In addition, baseline ECFC functional characteristics may predict response to exercise, suggesting that mechanisms or substances modulating ECFC colony formation and function may be essential factors that affect an individual’s response to exercise.

Authors: Tan, CMJ

• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: exercise; proteomics; pulse wave velocity; retinal microvasculature; endothelial colony-forming cells; hypertension
• Subjects: Blood pressure; Hypertension; Pulse wave velocity; Endothelial progenitor cells; Vascular endothelial cells; Endothelial cells; Micro-vasculature