The Role of Leukocytes in Diabetic Cardiomyopathy

Abstract

Diabetes is predominant risk factor for cardiovascular diseases such as myocardial infarction and heart failure. Recently, leukocytes, particularly neutrophils, macrophages, and lymphocytes, have become targets of investigation for their potential role in a number of chronic inflammatory diseases such as diabetes and heart failure. While leukocytes contribute significantly to the progression of diabetes and heart failure individually, understanding their participation in the pathogenesis of diabetic heart failure is much less understood. The present review summarizes the role of leukocytes in the complex interplay between diabetes and heart failure, which is critical to the discovery of new targeted therapies for diabetic cardiomyopathy.

Keywords: diabetes; heart failure; inflammation; leukocyte; lymphocyte.

FIGURE 1

Schematic diagram depicting infiltration of leukocytes from the circulation and their role in the diabetic cardiomyopathy (DCM). In DCM, a number of local processes are activated by glucose metabolites, reactive oxygen species (ROS) and pro-inflammatory cytokines together with accumulation of neutrophils and macrophages into the lesion site. Upon infiltration, neutrophils release extracellular traps (NETs) which induce sustained inflammation. Activated macrophages phagocytose cellular debris and also release pro-inflammatory cytokines and growth factors which activates fibroblasts to induce fibrosis. Th1 cells secrete pro-inflammatory cytokines which further exacerbate the inflammation in DCM whereas Treg cells secrete anti-inflammatory cytokines, where the ratio of pro-/anti-inflammatory cytokines may predict the progression of DCM. Abbreviations: ap-NT, apoptotic neutrophils; B cells, B lymphocytes; CM, cardiomyocytes; End, endothelial cells; FB, Fibroblast; G-Mets, Glucose metabolites; In-CM, Injured cardiomyocytes; ICAM1, Intracellular adhesion molecule 1; IL6, Interleukin 6; IL1β, Interleukin 1 beta; IFNγ, Interferon gamma; M1, pro-inflammatory macrophages; Mo, monocytes; Mϕ, activated macrophages; NETs, Neutrophils extracellular traps; NT, neutrophils; ROS, reactive oxygen species; Th1, T helper cells 1; Treg, T regulatory cells; VCAM1, vascular cell adhesion molecule 1.