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

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-fluorodeoxyglucose (F-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 F-FDG positron emission tomographic/computed tomographic imaging. Coronary vasoconstricting responses to serotonin were significantly enhanced at the EES edges compared with the control site (<0.01; n=40). Notably, in vivo and ex vivo F-FDG positron emission tomographic/computed tomographic imaging and autoradiography showed enhanced F-FDG uptake and its accumulation in PVAT at the EES edges compared with the control site, respectively (both <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 <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-FDG positron emission tomographic imaging is useful for assessment of coronary PVAT inflammation.