Site-specific impairment of perivascular adipose tissue on advanced atherosclerotic plaques using multimodal nonlinear optical imaging

Significance Perivascular adipose tissue (PVAT), adipose tissue surrounding blood vessels, has been reported to secrete inflammatory cytokines and adipokines in a paracrine/autocrine manner to regulate the vascular system in healthy and diseased states. However, how PVAT locally and spatially controls vascular functions as atherosclerosis progresses remains unknown. Using multimodal nonlinear optical imaging and an ex vivo assay, we found that PVAT changed differentially from the initial to advanced stages. Interestingly, PVAT at the atherosclerotic plaques showed highly agglomerated lipid droplets and increased fibrosis, suggesting spatial impairment. Our results provide a new concept of PVAT as modulating a direct interaction between the adipose tissue and cardiovascular system.