Diabetes mellitus is associated with increased cardiovascular risk, partly driven
by endothelial dysfunction, as well as vascular inflammation, leading to
accelerated atherosclerosis. This study initially investigated the expression and
function of miR-25-3p, a diabetes-associated miRNA in literature, using
experimental cell culture approaches and bulk-RNA sequencing. Functional
assays linked miR-25-3p to endothelial adhesion capacity, suggesting a
potential role in angiogenesis and broader endothelial biology.
To extend this into a more biologically relevant human context, miRNA profiling
was then performed in endothelial cells isolated from patients with diabetes,
allowing unbiased assessment of diabetes-associated miRNA perturbations.
miRNA sequencing identified a wide range of differentially expressed miRNAs,
from which a subset was chosen for qPCR validation, with two demonstrating
significant disease associated differences (miR-28-3p, and miR-548g-5p).
Functional enrichment analysis of predicted high-confidence targets of these
miRNAs indicated potential involvement in pathways related to endothelial
dysfunction and inflammation.
To place these findings in a broader vascular context, I integrated
transcriptomic data from two arterial beds, to identify perturbations shared
across the arterial tree. To assess translational relevance, arterial
transcriptomic hits were further assessed, where possible, in their plasma
protein form. Four proteins (ACP5, LILRA5, PSME2 and LEFTY2) showed
consistent diabetes-associated expression in both arterial walls and circulating
plasma. These proteins were associated with atherosclerotic cardiovascular risk
factors, clinical events, with two (ACP5 and LILRA5) showing promise for
prediction of cardiovascular disease when added to a clinical score.
Overall, these findings highlight the value of integrating miRNA profiling, arterial
transcriptomics and plasma proteomics in the study of diabetic cardiovascular
disease. Together, these complementary approaches may support biomarker
discovery, mechanistic understanding, and the development of future precision
therapeutic strategies for cardiovascular disease.
