Coronary artery disease (CAD) genetic predisposition and atherosclerotic plaque gene expression patterns, the role of sex in plaque gene regulation
Summary
This study showed that there is an association between genetic predisposition and some atherogenic transcriptional states of plaque in patients undergoing carotid endarterectomy, with immune processes, extracellular matrix and smooth muscle cell biology standing out as most associated. Furthermore, this study further supports that sex plays a role in this relationship with males presenting overall lower genetic risk in this carotid endarterectomy cohort. Sex also influences the shape in which these transcriptional states present themselves. In males the gene regulatory networks enriched in immune processes were identified as the strongest associated with genetic predisposition, while in females it was the gene regulatory networks involved in the SMC and ECM biology. Lastly, in males the difference in cell-type proportions seem to drive the association between the genetic predisposition and the module expression, while in females, cell-type proportions could not explain the associations found. Future studies should focus on unraveling the specific biological processes that lead to differential disease progression in males and females in order to better predict and treat CAD and move towards a more personalized framework for atherosclerosis disease.