Insulin use promotes pro-inflammatory changes in the transcriptome of atherosclerotic plaques in patients with diabetes mellitus.

Background: Diabetes Mellitus is associated with increased risk of myocardial infarctions and strokes due to accelerated atherosclerotic plaque development and rupture. The mechanisms driving plaque rupture in the diabetic setting remain unclear. Methods: We sequenced ribosome-depleted total RNA from carotid plaques obtained from diabetic subjects undergoing carotid endarterectomy with high-grade stenosis, who either recently experienced a carotid-related ischemic cerebrovascular event (Symptomatic, Results: Principal component analysis of the most variable transcripts demonstrated that sex and insulin use, rather than plaque rupture status, were the major contributors to the variability in the dataset. Hierarchical clustering further highlighted the importance of these factors in the dataset but also included two clusters whose expression was elevated in the symptomatic group. These clusters were enriched with transcripts for immunoglobulins and matrix metalloproteinases, suggesting increased B-cell infiltration and extracellular matrix degradation in the symptomatic plaques. We identified only two transcripts, Conclusions: Thus, insulin use significantly impacts the transcriptome of atherosclerotic plaques, promoting vascular inflammation.