Cardiac Lymphatic Dysfunction Causes Drug-Eluting Stent-Induced Coronary Hyperconstricting Responses in Pigs In Vivo

Hirokazu Amamizu, Yasuharu Matsumoto, Susumu Morosawa, Kazuma Ohyama, Hironori Uzuka, Michinori Hirano, Kensuke Nishimiya, Yusuke Gokon, Tomomi Watanabe-Asaka, Moyuru Hayashi, Satoshi Miyata, Takashi Kamei, Yoshiko Kawai, Hiroaki Shimokawa

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Objective- We have previously demonstrated that coronary adventitial inflammation plays important roles in the pathogenesis of coronary vasomotion abnormalities, including drug-eluting stent (DES)-induced coronary hyperconstricting responses. Importantly, the adventitia also harbors lymphatic vessels, which may prevent inflammation by transporting extravasated fluid and inflammatory cells. We thus aimed to examine the roles of coronary adventitial lymphatic vessels in the pathogenesis of DES-induced coronary hyperconstricting responses in a porcine model in vivo. Approach and Results- We performed 2 experimental studies. In protocol 1, 15 pigs were divided into 3 groups with or without DES and with bare metal stent. Nonstented sites 20 mm apart from stent implantation also were examined. In the protocol 2, 12 pigs were divided into 2 groups with or without lymphatic vessels ligation followed by DES implantation at 2 weeks later (n=6 each). We performed coronary angiography 4 weeks after DES implantation, followed by immunohistological analysis. In protocol 1, the number and the caliber of lymphatic vessels were greater at only the DES edges after 4 more weeks. In protocol 2, coronary hyperconstricting responses were further enhanced in the lymphatic vessels ligation group associated with adventitial inflammation, Rho-kinase activation, and less adventitial lymphatic vessels formation. Importantly, there were significant correlations among these inflammation-related changes and enhanced coronary vasoconstricting responses. Conclusions- These results provide evidence that cardiac lymphatic vessel dysfunction plays important roles in the pathogenesis of coronary vasoconstrictive responses in pigs in vivo.

Original languageEnglish
Pages (from-to)741-753
Number of pages13
JournalArteriosclerosis, thrombosis, and vascular biology
Volume39
Issue number4
DOIs
Publication statusPublished - 2019 Apr 1

Keywords

  • Rho kinase
  • coronary vasospasm
  • drug-eluting stent
  • inflammation
  • lymph

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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