T Cells in the Spotlight: A Multi-Omics Examination of Erosional & Ruptured Acute Coronary Syndromes

Acute coronary syndromes (ACS) are a significant cause of global mortality 1. ACS is characterized by the sudden interruption of blood flow to the heart muscle. Plaque rupture and plaque erosion are two mechanisms involved in ACS, leading to thrombus formation and myocardial ischemia. The global burden of ACS carries significant implications for public health, quality of life, and socioeconomic costs. In 2017, ACS accounted for an estimated 9.5 million global deaths, comprising 16% of all yearly fatalities 13. The total economic burden of ACS is $150 billion in the United States annually, with a direct medical cost estimated at $75 billion 14. Yet, an epidemiological transition for low- and middle-income countries as they continue to grow economically and undergo lifestyle changes warrants concern, especially for populations not typically associated with coronary artery disease, such as younger adults and women. While the main mechanisms of plaque rupture are understood, the underlying mechanisms of both plaque erosion and ruptured plaque remain unclear. This study aims to investigate the molecular mechanisms of erosional and ruptured plaque using a unique multi-omic approach of cellular indexing of transcriptomes and epitopes combined with single-cell T-cell receptor sequencing. This investigation unearthed a notable enrichment of TH17 cells in erosional ACS when compared to rupture and chronic coronary syndrome. This discovery, coupled with the observed enrichment of ruptured CD4+ TTE cells relative to erosion, hints at the multifaceted roles that T-cells play in both rupture and erosion mechanisms. Further findings on the upregulation of Integrin α6 and gene ontology results of cell adhesion dynamics for TH17 cell’s function depict a critical role of TH17 on laminin-rich structures such as blood vessels. Furthermore, via the integration of t-cell receptor repertoire information and the investigation of erosional and ruptured plaque public clonotypes, a narrative of common antigen exposure in erosional plaque depicted itself.