Abstract 15655
A Novel Large Animal Model of Accelerated Human-Like Coronary In-stent Neoatherosclerosis Formation
- Li, Yuxin
- Haruta, Hironori
- Fuchimoto, Daiichiro
- Suzuki, Shunichi
- Satou, Kazumi
- Kitano, Daisuke
- Takayama, Tadateru
- Hiro, Takafumi
- Kawakami, Rika
- Hirota, Seiichi
- Matsumoto, Taro
- Hao, Hiroyuki
- Onishi, Akira
- Hirayama, Atsushi
Introduction: Our current understanding of coronary in-stent atherosclerosis derives solely from pathology and retrospective observational studies, all clinical, which provide only a single snapshot of atherosclerotic lesion evolution. To understand the natural history of and the histopathologic mechanisms responsible for in-stent neoatherosclerosis, an animal model in which coronary in-stent restenosis develops rapidly is needed. We created a low-density lipoprotein receptor knockout (LDLR–/–) miniature pig with human-like unstable coronary plaques. Using the LDLR–/– miniature pig, we then aimed to create a large animal model that can be used to study rapid coronary in-stent neoatherosclerosis formation.
Methods and Results: Three-month-old LDLR–/– miniature pigs were, for 4 months, fed an atherosclerotic diet consisting of 15% fat and 1.5% cholesterol, and human-like unstable plaques developed in the coronary arteries of these pigs. Animals were chosen randomly, intravascular ultrasound (IVUS) was performed, and a Xience V everolimus-eluting coronary stent (Xience) or Absorb bioresorbable vascular scaffold (Abbott) was implanted in the coronary arteries at lesions with plaques. The animals were given aspirin (81 mg) and clopidogrel (75 mg) orally 3 days prior to implant and then daily throughout the follow-up period. The atherosclerotic diet was continued after stent implantation. Four months after implantation, the stent-implanted arteries were dissected for histologic examination. Histological staining revealed inflammatory cell infiltrates, fibrin deposits, fragmented calcifications, and foamy macrophage clusters in the peri-strut region in both Absorb- and Xience-implanted arteries. No stent thrombosis was evident in either the Absorb- or Xience-implanted arteries. Long-term continuous observation of vascular response and in-stent neoatherosclerosis by means of IVUS, angioscopy, and optical coherence tomography is in process.
Conclusions: We succeeded in creating a large animal model of rapid coronary in-stent neoatherosclerosis that mimics patients’ late vascular response to stent implantation and that can be used to investigate development of in-stent neoatherosclerosis.