Abstract
Background: Recent studies suggested that perivascular adipose tissue (PVAT) play important roles as a source of various inflammatory mediators in the pathogenesis of cardiovascular disease. We thus tested our hypothesis that inflammatory changes in the coronary PVAT are associated with coronary hyperconstricting responses after drug-eluting stent (DES) implantation by using FDG PET. Methods: 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. After 1 month, coronary vasoconstricting responses to intracoronary serotonin were examined by coronary angiography in vivo, followed by FDG PET/CT ex vivo imaging and autoradiography for measurement of FDG uptake. Results: Coronary vasoconstricting responses were significantly enhanced at the edges of the EES site compared with the control site (P<0.01, n=40) (Figures A-C). Notably, FDG PET/CT imaging showed enhanced FDG uptake at the EES-implanted coronary segment with significant association between the target to background ratio and the extent of coronary vasoconstricting responses (P<0.01) (Figures D-F). In addition, autoradiography showed that the FDG accumulation was markedly enhanced at the edge of the EES site compared with the control site and was significantly associated with the extent of coronary vasoconstricting responses (P<0.01) (Figures G-J, O). Furthermore, histological analysis and RT-PCR showed that the extent of inflammatory changes in the coronary PVAT were significantly enhanced at the edges of the EES site compared with the control site (Figures K-N). Conclusions: These results demonstrate for the first time that inflammatory changes in the coronary PVAT are involved in the pathogenesis of DES-induced coronary hyperconstricting responses in pigs in vivo and that FDG PET imaging may be useful for assessment of coronary PVAT inflammation.
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