Association of Coronary Perivascular Adipose Tissue Inflammation and Drug-Eluting Stent-Induced Coronary Hyperconstricting Responses in Pigs F-18-Fluorodeoxyglucose Positron Emission Tomography Imaging Study

作者：Ohyama Kazuma; Matsumoto Yasuharu; Amamizu Hirokazu; Uzuka Hironori; Nishimiya Kensuke; Morosawa Susumu; Hirano Michinori; Watabe Hiroshi; Funaki Yoshihito; Miyata Satoshi; Takahashi Jun; Ito Kenta; Shimokawa Hiroaki^*

来源：Arteriosclerosis, Thrombosis, and Vascular Biology, 2017, 37(9): 1757-+.

DOI：10.1161/ATVBAHA.117.309843

• adipose tissue
• coronary angiography
• drug-eluting stents
• inflammation
• positron-emission tomography

Objective-Although coronary perivascular adipose tissue (PVAT) may play important roles as a source of inflammation, the association of coronary PVAT inflammation and coronary hyperconstricting responses remains to be examined. We addressed this important issue in a porcine model of coronary hyperconstricting responses after drug-eluting stent implantation with F-18-fluorodeoxyglucose (F-18-FDG) positron emission tomographic imaging.
Approach and Results-An everolimus-eluting stent (EES) was randomly implanted in pigs into the left anterior descending or the left circumflex coronary artery while nonstented coronary artery was used as a control. After 1 month, coronary vasoconstricting responses to intracoronary serotonin (10 and 100 mu g/kg) were examined by coronary angiography in vivo, followed by in vivo and ex vivo F-18-FDG positron emission tomographic/computed tomographic imaging. Coronary vasoconstricting responses to serotonin were significantly enhanced at the EES edges compared with the control site (P<0.01; n=40). Notably, in vivo and ex vivo F-18-FDG positron emission tomographic/computed tomographic imaging and autoradiography showed enhanced F-18-FDG uptake and its accumulation in PVAT at the EES edges compared with the control site, respectively (both P<0.05). Furthermore, histological and reverse transcription polymerase chain reaction analysis showed that inflammatory changes of coronary PVAT were significantly enhanced at the EES edges compared with the control site (all P<0.01). Importantly, Rho-kinase expressions (ROCK1/ROCK2) and Rho-kinase activity (phosphorylated myosin phosphatase target subunit-1) at the EES edges were significantly enhanced compared with the control site.
Conclusions-These results indicate for the first time that inflammatory changes of coronary PVAT are associated with drug-eluting stent-induced coronary hyperconstricting responses in pigs in vivo and that F-18-FDG positron emission tomographic imaging is useful for assessment of coronary PVAT inflammation.
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• 出版日期2017-9