Faculty of Health and Medicine, School of Medical Sciences, University of Sydney, Sydney, NSW, Australia.
Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.
PLoS One. 2023 Aug 17;18(8):e0290342. doi: 10.1371/journal.pone.0290342. eCollection 2023.
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.
在我们目前对血管再狭窄的认识中，啮齿动物的动脉损伤模型非常有价值，并且在心血管疾病的血管内介入治疗的发展中继续发挥作用。血管壁的机械扩张和血管内皮的剥脱是大多数临床病理学中观察到的两种主要的血管损伤模式，对于可重复的进行性新生内膜增生模型的建立至关重要。目前在这个研究领域占主导地位的模型是小鼠线颈动脉或股动脉损伤和大鼠颈动脉球囊损伤。虽然这些模型能同时引起血管壁扩张和管腔内皮剥脱，但每个模型都存在局限性，需要使用互补的损伤模型来解决。由于血管直径小，小鼠的线损伤技术要求高且操作复杂，而大鼠的球囊损伤需要永久性血管结扎和破坏内源性血流。具有可重复性、便利性以及与血管内损伤的病理生理学相关性更高的血管损伤互补模型，将允许在基础和转化研究中更好地研究新生内膜增生。在这项研究中，我们开发了一种新的手术模型，该模型通过微夹和标准针导管经动脉切开术插入大鼠颈总动脉，使用顺序步骤引起血管扩张和内皮剥脱损伤，而无需永久性结扎分支动脉。损伤后 2 周，该模型引起的新生内膜增生具有高度可重复性，且再内皮化率与当前的线和球囊损伤模型相似。此外，对平滑肌细胞表型特征、炎症反应和发育中的新生内膜中的细胞外基质的评估表明，我们的模型复制了与再狭窄相关的血管重塑结果，这些结果在新的抗再狭窄治疗的开发中越来越受到关注。
