Department of Vascular Surgery and Kidney Transplantation, University Hospital of Strasbourg, France (A.L., S.H.K.).
Research Unit 3072 Mitochondria, Oxidative Stress and Muscular Plasticity, Strasbourg Biomedicine Research Center, France (A.L., S.H.K.).
Arterioscler Thromb Vasc Biol. 2024 Nov;44(11):2264-2270. doi: 10.1161/ATVBAHA.124.321163. Epub 2024 Oct 23.
More than 200 million people worldwide have peripheral artery disease (PAD). PAD affects the quality of life and is associated with significant morbidity and mortality. Standard treatment for severe cases of PAD is surgical or endovascular revascularization. However, up to 30% of patients are not candidates for open or endovascular procedures, due to high operative risk or unfavorable vascular involvement. Furthermore, revascularization procedures may be insufficient to adequately improve microvascular tissue perfusion, wound healing, or limb salvage. Accordingly, regardless of advances in treatment modalities, outcomes of patients with PAD have remained unfavorable. Therefore, new medical therapeutic approaches are much needed. Small animal models are indispensable tools for the understanding of PAD physiopathology and the development of novel medical therapies.
Development of animal models that more closely mimic the pathophysiology (with occlusive atherothrombosis and chronic development of limb ischemia) can incorporate the cardiovascular risk factors associated with this disease state, and focus on more clinically relevant outcomes is critical. In practice, this means using both animals that develop atherosclerosis and methods for the application of gradual arterial occlusion to induce hind limb ischemia. Doing so will likely help identify novel targets for intervention and overcome some principal challenges confronted by previous clinical trials. While various rodent models are discussed, the optimal animal model is yet to be defined.
全球有超过 2 亿人患有外周动脉疾病（PAD）。PAD 会影响生活质量，并且与较高的发病率和死亡率密切相关。严重 PAD 的标准治疗方法是手术或血管内血运重建。然而，由于高手术风险或血管情况不佳，多达 30%的患者不适合进行开放或血管内手术。此外，血运重建手术可能不足以充分改善微血管组织灌注、伤口愈合或肢体挽救。因此，无论治疗方式如何进步，PAD 患者的预后仍然不佳。因此，非常需要新的医疗治疗方法。小动物模型是理解 PAD 病理生理学和开发新型医学治疗方法不可或缺的工具。
开发更能模拟病理生理学（伴闭塞性动脉粥样硬化和肢体缺血的慢性发展）的动物模型，可以纳入与该疾病状态相关的心血管危险因素，并专注于更具临床相关性的结果，这一点至关重要。实际上，这意味着同时使用会发生动脉粥样硬化的动物和逐渐进行动脉闭塞以诱导后肢缺血的方法。这样做可能有助于确定干预的新靶点，并克服以前临床试验面临的一些主要挑战。虽然讨论了各种啮齿动物模型，但仍有待确定最佳动物模型。
