Targeting trained immunity and immunometabolic pathways with emerging immunomodulatory therapies may offer novel opportunities to halt or reverse diabetic cardiomyopathy progression.
Targeting trained immunity and immunometabolic pathways represents a promising therapeutic strategy to halt or reverse diabetic cardiomyopathy progression.
Diabetic cardiomyopathy (DCM) is a specific cardiac complication of diabetes that occurs independently of hypertension and coronary artery disease. Beyond metabolic disturbance, chronic hyperglycemia triggers immune dysfunction, contributing to myocardial inflammation, remodeling, and contractile impairment. This review highlights the critical roles of multiple immune cell populations-including monocytes, macrophages, mast cells, neutrophils, and T lymphocytes-in the pathogenesis of DCM, and frames DCM as an immunometabolic disorder driven in part by trained immunity. Hyperglycemia enhances glycolysis in macrophages and neutrophils, leading to the accumulation of acetyl-CoA that serves as a substrate for histone acetyltransferases. The resulting hyperacetylation of histone H3 locks immune cells into a pro-inflammatory state even after glucose levels normalize and amplifies inflammasome activation via the NLRP3 pathway, thereby coupling metabolic reprogramming to epigenetic reprogramming and sustaining chronic inflammation. In parallel, hyperglycemia-induced metabolic changes promote reactive oxygen species (ROS) production and upregulate S100A8/A9 expression. The S100A8/A9 heterodimer engages the receptor for advanced glycation end products (RAGE) on myeloid progenitors, driving the expansion of monocytes/macrophages and pro-inflammatory neutrophils and further fueling adverse cardiac remodeling. We also summarize emerging immunomodulatory therapies, including anti-cytokine strategies, inhibitors of inflammatory signaling pathways, mesenchymal stromal cell (MSC)-based interventions, other cellular treatments, and nanotechnology-enabled delivery platforms, which have shown promising anti-inflammatory and cardioprotective effects in preclinical models and early clinical studies. Targeting trained immunity and immunometabolic pathways may offer novel opportunities to halt or even reverse DCM progression.
Lv et al. (Fri,) conducted a review in Diabetic cardiomyopathy. Immunomodulatory therapies was evaluated. Targeting trained immunity and immunometabolic pathways with emerging immunomodulatory therapies may offer novel opportunities to halt or reverse diabetic cardiomyopathy progression.