Abstract

Background: Recent studies implicated that perivascular adipose tissue (PVAT) plays an important role in cardiovascular disease as a source of various inflammatory mediators with resultant coronary vasomotion abnormalities. In this study, we examined whether inflammatory changes in the PVAT are associated with coronary hyperconstricting responses after drug-eluting stent (DES) implantation in pigs in vivo. Methods and Results: Everolimus-eluting stents (EES) were randomly implanted in pigs into either the left anterior descending or circumflex coronary artery while non-stented artery was used as a control. At 1 month after the implantation, coronary vasoconstricting responses to intracoronary serotonin (100 μg/kg) were examined by coronary angiography in vivo. Then, stented vessels were harvested for immunohistological study for inflammatory changes in the PVAT at the stent edges. Coronary vasoconstricting responses to serotonin were significantly enhanced at the edges of the EES site as compared with the control site (P<0.05, n=12). Histological analysis showed that the extent of inflammatory changes in the PVAT as evaluated by CD68 (macrophage maker) and interleukin-1β (IL-1β) were significantly enhanced at the EES site compared with the control site (both P<0.05) (Figure). Furthermore, there were significant positive correlations between the extent of inflammatory changes in the PVAT and that of coronary vasoconstricting responses (both P<0.001) (Figure). Conclusions: These results suggest that inflammatory mediators in the PVAT (e.g. macrophages, IL-1β) are involved in the pathogenesis of DES-induced coronary hyperconstricting responses in pigs in vivo.

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