Endothelial Progenitor and Vascular Dysfunction in Infants of Diabetic Mothers

Project: Research project

Description

DESCRIPTION (provided by applicant): Significant evidence demonstrates that an adverse in utero environment increases offspring risk for vascular disease. While initial reports focused on growth restricted infants, data suggest that maternal diabetes (DM) predisposes offspring to vascular disease. Together these data suggest that the fetal vasculature is highly susceptible to injury. A critical component of vascular health is intact endothelial function. Homeostatic regulation of the endothelium requires dynamic interactions between endothelial cells and cells circulating in the blood to sustain endothelial function. Importantly, endothelial progenitor cells (EPCs) orchestrate vascular repair and vessel formation. Additionally, numerous studies in adults demonstrate a correlation between reduced peripheral blood EPC numbers and function with increased vascular disease risk. However, no studies have examined whether a similar correlation exists in children. Together these data form the basis for our overall hypothesis. We hypothesize that a maternal type 2 DM (T2DM) intrauterine environment subjects the fetus to significant stress resulting in decreased EPC numbers, loss of EPC functional capacity, and increased risk for endothelial dysfunction in offspring. EPC subpopulations can be identified by culture methods and flow cytometry. Two EPC subpopulations with distinct functional properties have been reported. However, few studies have evaluated the function of these EPCs from pediatric subjects, despite data indicating that both EPC types are operative in vascular repair. Studies outlined in this application will directly interrogate whether dysfunction of both EPC subpopulations are involved in endothelial dysfunction of offspring from T2DM pregnancies and examine the contribution of premature aging in the functional capacity of EPCs. Elucidating the underlying mechanisms responsible for the increased risk of vascular disease in offspring of T2DM mothers is paramount to finding potential preventative strategies. Further, pediatric studies offer the potential to identify biomarkers of vascular disease risk such that early interventions may be implemented to disrupt this pathology. PUBLIC HEALTH RELEVANCE: In this application, we will directly interrogate whether dysfunction of endothelial progenitor cells are involved in endothelial dysfunction of offspring from mothers with type 2 diabetes. Elucidating the underlying mechanisms responsible for the increased risk of vascular disease in offspring of type 2 diabetic mothers is paramount to finding potential preventative strategies.
StatusFinished
Effective start/end date8/1/095/31/14

Funding

  • National Institutes of Health: $380,274.00
  • National Institutes of Health: $547,916.00
  • National Institutes of Health: $366,227.00
  • National Institutes of Health: $182,832.00

Fingerprint

Blood Vessels
Mothers
Vascular Diseases
Endothelial Progenitor Cells
Cell Count
Pediatrics
Premature Aging
Type 2 Diabetes Mellitus
Endothelium
Blood Cells
Flow Cytometry
Fetus
Endothelial Cells
Biomarkers
Pathology
Pregnancy
Health
Wounds and Injuries
Growth

ASJC

  • Medicine(all)