Departments of Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University Parkville Campus, Australia.
Diabetes, Monash University, Clayton, Victoria 3800, Australia.
Clin Sci (Lond). 2021 Jun 11;135(11):1369-1387. doi: 10.1042/CS20210052.
Diabetes increases the prevalence of heart failure by 6-8-fold, independent of other comorbidities such as hypertension and coronary artery disease, a phenomenon termed diabetic cardiomyopathy. Several key signalling pathways have been identified that drive the pathological changes associated with diabetes-induced heart failure. This has led to the development of multiple pharmacological agents that are currently available for clinical use. While fairly effective at delaying disease progression, these treatments do not reverse the cardiac damage associated with diabetes. One potential alternative avenue for targeting diabetes-induced heart failure is the use of adeno-associated viral vector (AAV) gene therapy, which has shown great versatility in a multitude of disease settings. AAV gene therapy has the potential to target specific cells or tissues, has a low host immune response and has the possibility to represent a lifelong cure, not possible with current conventional pharmacotherapies. In this review, we will assess the therapeutic potential of AAV gene therapy as a treatment for diabetic cardiomyopathy.
糖尿病使心力衰竭的患病率增加 6-8 倍，与高血压和冠状动脉疾病等其他合并症无关，这种现象称为糖尿病心肌病。已经确定了几个关键的信号通路，这些通路驱动与糖尿病引起的心力衰竭相关的病理变化。这导致了多种药理学药物的开发，这些药物目前可用于临床使用。虽然这些治疗方法在延缓疾病进展方面相当有效，但它们不能逆转与糖尿病相关的心脏损伤。一种针对糖尿病性心力衰竭的潜在替代方法是使用腺相关病毒 (AAV) 基因治疗，这种方法在多种疾病环境中表现出了巨大的多功能性。AAV 基因治疗有可能针对特定的细胞或组织，具有低宿主免疫反应的可能性，并有可能代表一种终身治愈，这是目前的常规药物治疗所不可能实现的。在这篇综述中，我们将评估 AAV 基因治疗作为治疗糖尿病性心肌病的治疗潜力。
