Cai Lu, Tan Yi, Islam Md Shahidul, Horowitz Michael, Wintergerst Kupper A
Pediatric Research Institute, Departments of Pediatrics, Radiation Oncology, Pharmacology and Toxicology, University of Louisville, Wendy Novak Diabetes Institute, Norton Children's Hospital, Louisville, KY 40202, United States.
Department of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Durban 4000, KwaZulu-Natal, South Africa.
World J Diabetes. 2024 Aug 15;15(8):1659-1662. doi: 10.4239/wjd.v15.i8.1659.
Recently, the roles of pyroptosis, a form of cell death induced by activated NOD-like receptor protein 3 (NLRP3) inflammasome, in the pathogenesis of diabetic cardiomyopathy (DCM) have been extensively investigated. However, most studies have focused mainly on whether diabetes increases the NLRP3 inflammasome and associated pyroptosis in the heart of type 1 or type 2 diabetic rodent models, and whether various medications and natural products prevent the development of DCM, associated with decreased levels of cardiac NLRP3 inflammasome and pyroptosis. The direct link of NLRP3 inflammasome and associated pyroptosis to the pathogenesis of DCM remains unclear based on the limited evidence derived from the available studies, with the approaches of gene silencing or pharmaceutical application of specific inhibitors. We thus emphasize the requirement for more systematic studies that are designed to provide direct evidence to support the link, given that several studies have provided both direct and indirect evidence under specific conditions. This editorial emphasizes that the current investigation should be circumspect in its conclusion, , not overemphasizing its role in the pathogenesis of DCM with the fact of only significantly increased expression or activation of NLRP3 inflammasome and pyroptosis in the heart of diabetic rodent models. Only clear-cut evidence-based causative roles of NLRP3 inflammasome and pyroptosis in the pathogenesis of DCM can help to develop effective and safe medications for the clinical management of DCM, targeting these biomarkers.
最近，焦亡作为一种由活化的NOD样受体蛋白3（NLRP3）炎性小体诱导的细胞死亡形式，在糖尿病性心肌病（DCM）发病机制中的作用已得到广泛研究。然而，大多数研究主要集中在糖尿病是否会增加1型或2型糖尿病啮齿动物模型心脏中的NLRP3炎性小体及相关焦亡，以及各种药物和天然产物是否能预防DCM的发生，这与心脏NLRP3炎性小体和焦亡水平降低有关。基于现有研究所获得的有限证据，通过基因沉默或特定抑制剂的药物应用方法，NLRP3炎性小体及相关焦亡与DCM发病机制之间的直接联系仍不明确。鉴于已有多项研究在特定条件下提供了直接和间接证据，我们因此强调需要进行更系统的研究，以提供直接证据来支持这种联系。这篇社论强调，当前的研究在得出结论时应谨慎，不能仅因糖尿病啮齿动物模型心脏中NLRP3炎性小体和焦亡的表达或激活显著增加，就过分强调其在DCM发病机制中的作用。只有NLRP3炎性小体和焦亡在DCM发病机制中明确的基于证据的因果作用，才能有助于开发针对这些生物标志物的有效且安全的药物用于DCM的临床治疗。
