Omics Approaches Unveiling the Biology of Human Atherosclerotic Plaques

Atherosclerosis is a chronic inflammatory disease of the arterial wall, characterized by the buildup of plaques with the accumulation and transformation of lipids, immune cells, vascular smooth muscle cells, and necrotic cell debris. Plaques with collagen-poor thin fibrous caps infiltrated by macrophages and lymphocytes are considered unstable because they are at the greatest risk of rupture and clinical events. However, the current histologic definition of plaque types may not fully capture the complex molecular nature of atherosclerotic plaque biology and the underlying mechanisms contributing to plaque progression, rupture, and erosion. The advances in omics technologies have changed the understanding of atherosclerosis plaque biology, offering new possibilities to improve risk prediction and discover novel therapeutic targets. Genomic studies have shed light on the genetic predisposition to atherosclerosis, and integrative genomic analyses expedite the translation of genomic discoveries. Transcriptomic, proteomic, metabolomic, and lipidomic studies have refined the understanding of the molecular signature of atherosclerotic plaques, aiding in data-driven hypothesis generation for mechanistic studies and offering new prospects for biomarker discovery. Furthermore, advancements in single-cell technologies and emerging spatial analysis techniques have unveiled the heterogeneity and plasticity of plaque cells. This review discusses key omics-based discoveries that have advanced the understanding of human atherosclerotic plaque biology, focusing on insights derived from omics profiling of human atherosclerotic vascular specimens.