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
Published online Sep 15, 2024. doi: 10.4239/wjd.v15.i9.1847
Mechanism | Consequence | Effect on heart function | Ref. |
Increased M1 polarization by hyperglycemia: Activation of nuclear factor-kappaB and mitogen-activated protein kinases pathways | Increased production of pro-inflammatory cytokines (IL-1β, TNF-α) and enhanced generation of reactive oxygen species | Direct cardiomyocyte damage and impaired contractile function | [8,12] |
Impaired M2 polarization by hyperglycemia: Downregulation of IL-10 and TGF-β signaling | Reduced production of anti-inflammatory cytokines and impaired clearance of apoptotic cells and tissue repair | Perpetuation of inflammation and delayed wound healing | [7] |
NLRP3 inflammasome activation: Triggered by hyperglycemia and damage-associated molecular patterns | Processing and release of pro-inflammatory cytokine IL-1β | Amplification of inflammatory response and aggravated cardiac dysfunction | [12,13,22] |
M1 macrophage-mediated cardiomyocyte injury: Release of pro-inflammatory cytokines and reactive oxygen species | Direct damage to cardiomyocytes | Reduced contractility and pump function | [23] |
M1 macrophage-promoted fibrosis: Enhanced collagen deposition by fibroblasts | Myocardial stiffening and fibrosis | Impaired relaxation and filling of heart and decreased pump function | [11] |
Impaired apoptotic/necrotic cell clearance: Dysfunctional macrophages | Accumulation of cellular debris | Sustained inflammatory response and hindered tissue repair | [10] |
Drug class | Drug examples | Effects on macrophages | Related mechanisms | Ref. |
Dipeptidyl peptidase-4 inhibitors | Teneligliptin, linagliptin, sitagliptin | Reduce pro-inflammatory cytokine production (IL-1β, IL-6), promote M2 polarization, and inhibit NLRP3 inflammasome activation | Increased glucagon-like peptide-1 levels, reduced oxidative stress, and modulation of nuclear factor-kappaB signaling pathway | [3,14,24] |
Metformin | Metformin | Reduces M1 polarization, increases M2 polarization, suppresses nuclear factor-kappaB signaling, and inhibits mitochondrial dysfunction | AMPK activation, reduced reactive oxygen species generation, and modulation of metabolic pathways | [13,17] |
Sodium-glucose cotransporter 2 inhibitors | Dapagliflozin, empagliflozin | May indirectly affect macrophage function through improved cardiac function and reduced inflammation | Sodium-glucose cotransporter 2 inhibition leads to diuresis and natriuresis, and may improve cardiac remodeling | [18,25] |
Glucagon-like peptide-1 receptor agonists | Liraglutide, dulaglutide | Promote M2 polarization, reduce pro-inflammatory cytokine production, and may improve cardiac contractility | Reduce oxidative stress, and enhance insulin sensitivity | [26-28] |
Thiazolidinediones | Pioglitazone | Have anti-inflammatory properties, and improve insulin sensitivity | Peroxisome proliferator-activated receptor-γ activation, and reduced nuclear factor-kappaB signaling | [29,30] |
- Citation: Mohammadi S, Al-Harrasi A. Macrophage modulation with dipeptidyl peptidase-4 inhibitors: A new frontier for treating diabetic cardiomyopathy? World J Diabetes 2024; 15(9): 1847-1852
- URL: https://www.wjgnet.com/1948-9358/full/v15/i9/1847.htm
- DOI: https://dx.doi.org/10.4239/wjd.v15.i9.1847