Editorial
Copyright ©The Author(s) 2024.
World J Diabetes. Sep 15, 2024; 15(9): 1847-1852
Published online Sep 15, 2024. doi: 10.4239/wjd.v15.i9.1847
Table 1 Molecular mechanisms of macrophage dysfunction in diabetic cardiomyopathy
Mechanism
Consequence
Effect on heart function
Ref.
Increased M1 polarization by hyperglycemia: Activation of nuclear factor-kappaB and mitogen-activated protein kinases pathwaysIncreased production of pro-inflammatory cytokines (IL-1β, TNF-α) and enhanced generation of reactive oxygen speciesDirect cardiomyocyte damage and impaired contractile function[8,12]
Impaired M2 polarization by hyperglycemia: Downregulation of IL-10 and TGF-β signalingReduced production of anti-inflammatory cytokines and impaired clearance of apoptotic cells and tissue repairPerpetuation of inflammation and delayed wound healing[7]
NLRP3 inflammasome activation: Triggered by hyperglycemia and damage-associated molecular patternsProcessing and release of pro-inflammatory cytokine IL-1βAmplification of inflammatory response and aggravated cardiac dysfunction[12,13,22]
M1 macrophage-mediated cardiomyocyte injury: Release of pro-inflammatory cytokines and reactive oxygen speciesDirect damage to cardiomyocytesReduced contractility and pump function[23]
M1 macrophage-promoted fibrosis: Enhanced collagen deposition by fibroblastsMyocardial stiffening and fibrosisImpaired relaxation and filling of heart and decreased pump function[11]
Impaired apoptotic/necrotic cell clearance: Dysfunctional macrophagesAccumulation of cellular debrisSustained inflammatory response and hindered tissue repair[10]
Table 2 Effects of antidiabetic drugs on macrophage function in diabetic cardiomyopathy
Drug class
Drug examples
Effects on macrophages
Related mechanisms
Ref.
Dipeptidyl peptidase-4 inhibitorsTeneligliptin, linagliptin, sitagliptinReduce pro-inflammatory cytokine production (IL-1β, IL-6), promote M2 polarization, and inhibit NLRP3 inflammasome activationIncreased glucagon-like peptide-1 levels, reduced oxidative stress, and modulation of nuclear factor-kappaB signaling pathway[3,14,24]
MetforminMetforminReduces M1 polarization, increases M2 polarization, suppresses nuclear factor-kappaB signaling, and inhibits mitochondrial dysfunctionAMPK activation, reduced reactive oxygen species generation, and modulation of metabolic pathways[13,17]
Sodium-glucose cotransporter 2 inhibitorsDapagliflozin, empagliflozinMay indirectly affect macrophage function through improved cardiac function and reduced inflammationSodium-glucose cotransporter 2 inhibition leads to diuresis and natriuresis, and may improve cardiac remodeling[18,25]
Glucagon-like peptide-1 receptor agonistsLiraglutide, dulaglutidePromote M2 polarization, reduce pro-inflammatory cytokine production, and may improve cardiac contractilityReduce oxidative stress, and enhance insulin sensitivity[26-28]
ThiazolidinedionesPioglitazoneHave anti-inflammatory properties, and improve insulin sensitivityPeroxisome proliferator-activated receptor-γ activation, and reduced nuclear factor-kappaB signaling[29,30]