Decoding PVAT Complexity in Vascular Remodeling: Multimodal Single-Cell Technologies Unveil Novel Therapeutic Targets

Perivascular adipose tissue (PVAT) has emerged as a central regulator of vascular homeostasis in large arteries, with its dysfunction driving the pathogenesis of atherosclerosis, hypertension, and metabolic diseases. In the past, our understanding of PVAT was limited by bulk omics approaches that obscured the tissue's profound spatial, cellular, and functional heterogeneity. Here, we review how multimodal single-cell technologies, including single-cell RNA sequencing, spatial transcriptomics, and AI integration, are now decoding the PVAT ecosystem with unprecedented resolution. These approaches have generated an integrated atlas that reveals depot-specific cellular architectures, dynamic phenotypic plasticity, and spatially organized crosstalk between biological circuits that drive vasculopathy. We highlight novel biomarkers and actionable therapies emerging from these insights, such as Dpp4⁺ preadipocytes and BMP4-induced browning. Finally, we propose a translational roadmap that prioritizes human PVAT biobanking, CRISPR-based lineage tracing, and AI-driven modeling to transform these mechanistic discoveries into precision interventions. Ultimately, by establishing PVAT as a central orchestrator of vascular homeostasis, these single-cell insights provide the mechanistic foundation to therapeutically intercept cardiometabolic disease at its cellular source.