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

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

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1757-1764
Number of pages8
JournalArteriosclerosis, thrombosis, and vascular biology
Volume37
Issue number9
DOIs
Publication statusPublished - 2017 Sep 1

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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