Abstract
Background Perivascular adipose tissue ( PVAT ) is causally associated with vascular function and the pathogenesis of vascular disease in association with metabolically driven chronic inflammation called metaflammation. However, the difference in PVAT surrounding the coronary artery ( CA - PVAT ) and that surrounding the internal thoracic artery (ITA-PVAT), a vessel resistant to atherosclerosis, remains unclear. Herein, we investigated whether CA - PVAT , ITA - PVAT , and subcutaneous adipose tissue ( SCAT ) have distinct phenotypes. Methods and Results Fat pads were sampled from 44 patients (men/women, 36:8; age, 67±13 years) with CA disease who underwent elective CA bypass grafting. Adipocyte size in ITA - PVAT and that in CA - PVAT were significantly smaller than that in SCAT . A greater extent of fibrosis and increased gene expression levels of fibrosis-related molecules were observed in CA - PVAT than those in SCAT and those in ITA - PVAT . CA - PVAT exhibited more pronounced metaflammation, as indicated by a significantly larger extent of CD 68-positive and CD 11c-positive M1 macrophages, a lower ratio of CD 206-positive M2 to CD 11c-positive M1 macrophages, a lower gene expression level of adiponectin, and higher gene expression levels of inflammatory cytokines and inflammasome- and endoplasmic reticulum stress-related molecules, than did ITA - PVAT and SCAT . Expression patterns of adipocyte developmental and pattern-forming genes were totally different among SCAT , ITA - PVAT, and CA - PVAT . Conclusions The phenotype of ITA - PVAT is closer to that of SCAT than that of CA - PVAT , which may result from inherent differences in adipocytes. ITA - PVAT appears to be protected from metaflammation and consecutive adipose tissue remodeling, which may contribute to the decreased atherosclerotic plaque burden in the ITA.