The adipose tissue-plaque crosstalk: omics profiling of perivascular adipose tissues for understanding plaque stability.

Abstract

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of global morbidity and mortality, despite significant advances in lipid-lowering and cardiometabolic therapies. Increasing evidence indicates that atherosclerosis cannot be fully understood as a disease confined to the arterial wall, but rather reflects complex interactions between vascular, immune, metabolic, and perivascular compartments. Among these, perivascular adipose tissue (PVAT) has emerged as a critical regulator of vascular homeostasis and plaque biology due to its unique anatomical proximity and functional continuity with the vessel wall. This review summarises current knowledge on the role of PVAT in atherosclerosis, particularly insights gained through omics approaches. We explore how transcriptomics, proteomics, metabolomics, and lipidomics have advanced the structural and functional characterisation of PVAT, revealing pronounced cellular heterogeneity, depot-specific signatures, and dynamic phenotypic plasticity, including brown-to-white adipose tissue transitions. We further examine the molecular and cellular interfaces that mediate PVAT-vascular crosstalk and discuss how PVAT influences key processes relevant to plaque development and stability, including inflammation and immune signaling, extracellular matrix remodeling, cell differentiation and survival, and regulation of vascular tone. Importantly, emerging evidence supports bidirectional communication between PVAT and atherosclerotic plaques, establishing maladaptive feedback loops that may sustain vascular inflammation and contribute to residual cardiovascular risk. Finally, we address translational implications, evaluating the potential of PVAT-derived biomarkers and the therapeutic targeting of PVAT-plaque interaction for improved risk stratification and the development of more precise, tissue-targeted interventions in ASCVD.