Highly reproducible rat arterial injury model of neointimal hyperplasia

Richard P Tan; Jui Chien Hung; Alex H P Chan; Angus J Grant; Matthew J Moore; Yuen Ting Lam; Praveesuda Michael; Steven G Wise

doi:10.1371/journal.pone.0290342

Highly reproducible rat arterial injury model of neointimal hyperplasia

PLoS One. 2023 Aug 17;18(8):e0290342. doi: 10.1371/journal.pone.0290342. eCollection 2023.

Authors

Richard P Tan^{1

2}, Jui Chien Hung^{1

2}, Alex H P Chan^{1

2}, Angus J Grant^{1

2}, Matthew J Moore^{1

2}, Yuen Ting Lam^{1

2}, Praveesuda Michael^{1

2}, Steven G Wise^{1

2}

Affiliations

¹ Faculty of Health and Medicine, School of Medical Sciences, University of Sydney, Sydney, NSW, Australia.
² Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.

Abstract

Models of arterial injury in rodents have been invaluable to our current understanding of vessel restenosis and play a continuing role in the development of endovascular interventions for cardiovascular disease. Mechanical distention of the vessel wall and denudation of the vessel endothelium are the two major modes of vessel injury observed in most clinical pathologies and are critical to the reproducible modelling of progressive neointimal hyperplasia. The current models which have dominated this research area are the mouse wire carotid or femoral injury and the rat carotid balloon injury. While these elicit simultaneous distension of the vessel wall and denudation of the luminal endothelium, each model carries limitations that need to be addressed using a complementary injury model. Wire injuries in mice are highly technical and procedurally challenging due to small vessel diameters, while rat balloon injuries require permanent blood vessel ligation and disruption of native blood flow. Complementary models of vascular injury with reproducibility, convenience, and increased physiological relevance to the pathophysiology of endovascular injury would allow for improved studies of neointimal hyperplasia in both basic and translational research. In this study, we developed a new surgical model that elicits vessel distention and endothelial denudation injury using sequential steps using microforceps and a standard needle catheter inserted via arteriotomy into a rat common carotid artery, without requiring permanent ligation of branching arteries. After 2 weeks post-injury this model elicits highly reproducible neointimal hyperplasia and rates of re-endothelialisation similar to current wire and balloon injury models. Furthermore, evaluation of the smooth muscle cell phenotype profile, inflammatory response and extracellular matrix within the developing neointima, showed that our model replicated the vessel remodelling outcomes critical to restenosis and those becoming increasingly focused upon in the development of new anti-restenosis therapies.

Copyright: © 2023 Tan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carotid Artery, Common
Constriction, Pathologic
Hyperplasia
Mice
Neointima
Rats
Reproducibility of Results
Vascular System Injuries* / etiology

Grants and funding

This work was supported by the National Health and Medical Research Council (APP1162969; S.G.W.), funding from the Sydney Local Health District (S.G.W) and from NSW Health in the form of a NSW Cardiovascular Early-Mid Career Researcher Grant (S.G.W & R.P.T.). R.P.T. receives funding as a National Heart Foundation Postdoctoral Fellow. S.G.W receives funding as a National Heart Foundation Future Leader Fellow.