Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.
Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia; Department of Pharmacology, Monash University, Clayton, VIC 3800, Australia.
Trends Pharmacol Sci. 2022 Nov;43(11):940-956. doi: 10.1016/j.tips.2022.04.005. Epub 2022 Jun 30.
Patients with diabetes have an increased risk of developing heart failure, preceded by (often asymptomatic) cardiac abnormalities, collectively called diabetic cardiomyopathy (DC). Diabetic heart failure lacks effective treatment, remaining an urgent, unmet clinical need. Although structural and functional characteristics of the diabetic human heart are well defined, clinical studies lack the ability to pinpoint the specific mechanisms responsible for DC. Preclinical animal models represent a vital component for understanding disease aetiology, which is essential for the discovery of new targeted treatments for diabetes-induced heart failure. In this review, we describe the current landscape of preclinical DC models (genetic, pharmacologically induced, and diet-induced models), highlighting their strengths and weaknesses and alignment to features of the human disease. Finally, we provide tools, resources, and recommendations to assist future preclinical translation addressing this knowledge gap.
糖尿病患者发生心力衰竭的风险增加,心力衰竭之前通常会出现(无症状)心脏异常,统称为糖尿病心肌病(DC)。糖尿病性心力衰竭缺乏有效治疗方法,仍然是一个迫切需要解决的临床未满足需求。尽管糖尿病患者心脏的结构和功能特征已经得到很好的定义,但临床研究缺乏确定导致 DC 的具体机制的能力。临床前动物模型是理解疾病发病机制的重要组成部分,对于发现针对糖尿病性心力衰竭的新靶向治疗方法至关重要。在这篇综述中,我们描述了目前临床前 DC 模型(遗传、药理学诱导和饮食诱导模型)的现状,强调了它们的优缺点以及与人类疾病特征的一致性。最后,我们提供了工具、资源和建议,以协助未来解决这一知识差距的临床前转化。