TY - JOUR
T1 - Association of Coronary Perivascular Adipose Tissue Inflammation and Drug-Eluting Stent-Induced Coronary Hyperconstricting Responses in Pigs
T2 - 18F-Fluorodeoxyglucose Positron Emission Tomography Imaging Study
AU - Ohyama, Kazuma
AU - Matsumoto, Yasuharu
AU - Amamizu, Hirokazu
AU - Uzuka, Hironori
AU - Nishimiya, Kensuke
AU - Morosawa, Susumu
AU - Hirano, Michinori
AU - Watabe, Hiroshi
AU - Funaki, Yoshihito
AU - Miyata, Satoshi
AU - Takahashi, Jun
AU - Ito, Kenta
AU - Shimokawa, Hiroaki
N1 - Funding Information:
This work was supported, in part, by the grants-in-aid for the Scientific Research (18890018) and the Global COE Project (F02) and the grants-in-aid (H22-Shinkin-004) from the Japanese Ministry of Education, Culture, Sports, Science, and Technology, Tokyo, Japan (to H. Shimokawa) and the grant for young investigators of translational research from the Tohoku University Hospital (to Y. Matsumoto).
Publisher Copyright:
© 2017 American Heart Association, Inc.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - 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 18F-fluorodeoxyglucose (18F-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 μg/kg) were examined by coronary angiography in vivo, followed by in vivo and ex vivo 18F-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 18F-FDG positron emission tomographic/computed tomographic imaging and autoradiography showed enhanced 18F-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 18F-FDG positron emission tomographic imaging is useful for assessment of coronary PVAT inflammation.
AB - 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 18F-fluorodeoxyglucose (18F-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 μg/kg) were examined by coronary angiography in vivo, followed by in vivo and ex vivo 18F-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 18F-FDG positron emission tomographic/computed tomographic imaging and autoradiography showed enhanced 18F-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 18F-FDG positron emission tomographic imaging is useful for assessment of coronary PVAT inflammation.
KW - adipose tissue
KW - coronary angiography
KW - drug-eluting stents
KW - inflammation
KW - positron-emission tomography
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U2 - 10.1161/ATVBAHA.117.309843
DO - 10.1161/ATVBAHA.117.309843
M3 - Article
C2 - 28751570
AN - SCOPUS:85038398543
SN - 1079-5642
VL - 37
SP - 1757
EP - 1764
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
IS - 9
ER -