Carotid plaque rupture that results in stroke is accompanied by a transcriptome profile that is pro-inflammatory and thins the fibrous cap

The cause of myocardial infarction and ischemic stroke is rupture of an atherosclerotic plaque. The paucity of information from plaques at the time of rupture contributes to the mystery surrounding the molecular mechanisms of rupture. Carotid plaques from patients undergoing carotid endarterectomy with high-grade stenosis and either (1) a carotid-related ischemic cerebrovascular event within the previous 5 days ('recently ruptured,' n=6) or (2) an absence of a cerebrovascular event were obtained. Ribosome-depleted total RNA was then sequenced from the carotid plaques. Plaque rupture was identified as the major contributor to sample variability (23.2%) by principal component analysis, and transcripts linked to inflammation and extracellular matrix breakdown were more abundant in recently ruptured plaques. Differentiating the asymptomatic from the freshly burst plaques was accomplished using hierarchical clustering. Matrix metalloproteinases, interferon response genes, and transcripts for the function of immunoglobulins and B lymphocytes were also discovered to co-express in this analysis. The relevance of inflammation and the inhibition of proliferation and migration together with an increase in apoptosis were supported by analysis of the differentially expressed genes. This supports further research into the involvement of B lymphocytes and interferons in atherosclerotic plaque rupture and explains why the transcriptome of recently ruptured plaques is enriched with genes linked to inflammation and fibrous cap thinning.