National University of Singapore
DIABETES MELLITUS AND THE DYSREGULATION OF ANGIOGENESIS IN TUBERCULOSIS
Abstract
dc:description.abstractDiabetes mellitus (DM), characterized by chronic hyperglycemia, is a risk factor for tuberculosis (TB), contributing to more severe disease and poorer treatment outcomes. Angiogenesis plays a key role in TB immunopathology by supporting mycobacterial survival within granulomas, whereas DM-associated oxidative stress impairs normal angiogenic processes. I hypothesized that disrupted angiogenic regulation underlies the worsened outcomes observed in DM-TB comorbidity. To investigate this, I profiled angiogenic factors and matrix metalloproteinases in PBMCs and neutrophils stimulated with heat-killed Mycobacterium tuberculosis, alongside transcriptional analysis using single-cell RNA sequencing. Infection conditions were optimized based on reactive oxygen species production and cell viability. Following stimulation, a multiplex Luminex assay revealed early induction of angiogenic factors in both healthy and DM groups, with a trend toward reduced secretion in DM. scRNA-seq identified angiogenic gene signatures in select myeloid populations. In summary, this study provides insight into the early landscape of angiogenic signalling in DM-TB.
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- CHONG HAI TARNG