Atherosclerotic disease is a major cause of acute cardiovascular events. A deeper understanding of its underlying mechanisms will allow advancing personalized and patient-centered healthcare. Transcriptomic research has proven to be a powerful tool for unravelling the complex molecular pathways that drive atherosclerosis. However, low reproducibility of research findings and lack of standardization of procedures pose significant challenges in this field. In this review, we discuss how transcriptomic research can help in understanding the different phenotypes of the atherosclerotic plaque that contribute to the development and progression of atherosclerosis. We highlight the methodological challenges that need to be addressed to improve research outputs, and emphasize the importance of research protocols harmonization. We also discuss recent advances in transcriptomic research, including bulk or single-cell sequencing, and their added value in plaque phenotyping. Finally, we explore how integrated multiomics data and machine learning improve understanding of atherosclerosis and provide directions for future research.
