Development of Advanced Atherosclerotic Plaque by Injection of Inflammatory Proteins in a Rabbit Iliac Artery Model
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Purpose: Appropriate animal models of atherosclerotic plaque are crucial to investigating the pathophysiology of atherosclerosis, as well as for the evaluation of the efficacy and safety of vascular devices. We aimed to develop a novel animal model that would be suitable for the study of advanced atherosclerotic lesions in vivo. Materials and Methods: Atherosclerotic plaque was induced in 24 iliac arteries from 12 rabbits by combining a high cholesterol diet, endothelial denudation, and injection into the vessel wall with either saline (n=5), olive oil (n=6), or inflammatory proteins [n=13, high-mobility group protein B1 (HMGB1) n=8 and tumor necrosis factor (TNF)-α n=5] using a CricketTM Micro-infusion catheter. Optical coherence tomography (OCT) was performed to detect plaque characteristics after 4 weeks, and all tissues were harvested for histological evaluation. Results: Advanced plaque was more frequently observed in the group injected with inflammatory proteins. Macrophage infiltrationwas present to a higher degree in the HMGB1 and TNF-α groups, compared to the oil or saline group (82.1±5.1% and 94.6± 2.2% compared to 49.6±14.0% and 46.5±9.6%, p-value<0.001), using RAM11 antibody staining. On OCT, lipid rich plaques were more frequently detected in the inflammatory protein group [saline group: 2/5 (40%), oil group: 3/5 (50%), HMGB1 group: 6/8 (75%), and TNF-α group: 5/5 (100%)]. Conclusion: These data indicate that this rabbit model of atherosclerotic lesion formation via direct injection of pro-inflammatory proteins into the vessel wall is useful for in vivo studies investigating atherosclerosis.
Abstract
Purpose: Appropriate animal models of atherosclerotic plaque are crucial to investigating the pathophysiology of atherosclerosis, as well as for the evaluation of the efficacy and safety of vascular devices. We aimed to develop a novel animal model that would be suitable for the study of advanced atherosclerotic lesions in vivo. Materials and Methods: Atherosclerotic plaque was induced in 24 iliac arteries from 12 rabbits by combining a high cholesterol diet, endothelial denudation, and injection into the vessel wall with either saline (n=5), olive oil (n=6), or inflammatory proteins [n=13, high-mobility group protein B1 (HMGB1) n=8 and tumor necrosis factor (TNF)-α n=5] using a CricketTM Micro-infusion catheter. Optical coherence tomography (OCT) was performed to detect plaque characteristics after 4 weeks, and all tissues were harvested for histological evaluation. Results: Advanced plaque was more frequently observed in the group injected with inflammatory proteins. Macrophage infiltrationwas present to a higher degree in the HMGB1 and TNF-α groups, compared to the oil or saline group (82.1±5.1% and 94.6± 2.2% compared to 49.6±14.0% and 46.5±9.6%, p-value<0.001), using RAM11 antibody staining. On OCT, lipid rich plaques were more frequently detected in the inflammatory protein group [saline group: 2/5 (40%), oil group: 3/5 (50%), HMGB1 group: 6/8 (75%), and TNF-α group: 5/5 (100%)]. Conclusion: These data indicate that this rabbit model of atherosclerotic lesion formation via direct injection of pro-inflammatory proteins into the vessel wall is useful for in vivo studies investigating atherosclerosis.
참고문헌 (19)
- Arbab-Zadeh A, "Acute coronary events", Circulation, 125, pp.1147~1156 (2012)
- Otsuka F, "Clinical classification of plaque morphology in coronary disease", Nat Rev Cardiol, 11, pp.379~389 (2014)
- Virmani R, "Pathology of the vulnerable plaque", J Am Coll Cardiol, 47(8 Suppl), pp.C13~C18 (2006)
- Bentzon JF, "Mechanisms of plaque formation and rupture", Circ Res, 114, pp.1852~1866 (2014)
- Granada JF, "In vivo plaque characterization using intravascular ultrasound-virtual histology in a porcine model of complex coronary lesions", Arterioscler Thromb Vasc Biol, 27, pp.387~393 (2007)
- Phinikaridou A, "A robust rabbit model of human atherosclerosis and atherothrombosis", J Lipid Res, 50, pp.787~797 (2009)
- Granada JF, "Porcine models of coronary atherosclerosis and vulnerable plaque for imaging and interventional research", EuroIntervention, 5, pp.140~148 (2009)
- Fan J, "Rabbit models for the study of human atherosclerosis: from pathophysi-ological mechanisms to translational medicine", Pharmacol Ther, 146, pp.104~119 (2015)
- Granada JF, "Endovascular needle injection of cholesteryl linoleate into the arterial wall produces complex vascular lesions identifiable by intravascular ultrasound: early development in a porcine model of vulnerable plaque", Coron Artery Dis, 16, pp.217~224 (2005)
- Tellez A, "Intramural coronary lipid injection induces atheromatous lesions expressing proinflammatory chemokines: implications for the development of a porcine model of atherosclerosis", Cardiovasc Revasc Med, 12, pp.304~311 (2011)
- Ridker PM, "Anti-inflammatory therapies for cardiovascular disease", Eur Heart J, 35, pp.1782~1791 (2014)
- Stary HC, "A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association", Arterioscler Thromb Vasc Biol, 15, pp.1512~1531 (1995)
- Tearney GJ, "Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies:a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation", J Am Coll Cardiol, 59, pp.1058~1072 (2012)
- Tearney GJ, "OCT imaging of macrophages: a bright spot in the study of inflammation in human atherosclerosis", JACC Cardiovasc Imaging, 8, pp.73~75 (2015)
- McKellar GE, "Role for TNF in atherosclerosis? Lessons from autoimmune disease", Nat Rev Cardiol, 6, pp.410~417 (2009)
- Park S, "RAGE and cardiovascular disease", Front Biosci (Landmark Ed), 16, pp.486~497 (2011)
- Hirata Y, "HMGB1 plays a critical role in vascular inflammation and lesion formation via toll-like receptor 9", Atherosclerosis, 231, pp.227~233 (2013)
- Porto A, "Smooth muscle cells in human atherosclerotic plaques secrete and proliferate in response to high mobility group box 1protein", FASEB J, 20, pp.2565~2566 (2006)
- Kim JS, "Neointimal patterns obtained by optical coherence tomography correlate with specific histological components and neointimal proliferation in a swine model of restenosis", Eur Heart J Cardiovasc Imaging, 15, pp.292~298 (2014)