Inflammatory markers, oxidative stress, and mitochondrial dynamics: Repercussions on coronary artery disease in diabetes

Abstract

Inflammatory markers and mediators that affect the development of car-diovascular diseases have been the focus of recent scientific work. Thus, the purpose of this editorial is to promote a critical debate about the article titled "Nε-carboxymethyl-lysine and inflammatory cytokines, markers, and mediators of coronary artery disease progression in diabetes", published in the World Journal of Diabetes in 2024. This work directs us to reflect on the role of advanced glycation end products, which are pro-inflammatory products arising from the metabolism of fatty acids and sugars whose main marker in tissues is Nε-carboxymethyl-lysine (NML). Recent studies have linked high levels of pro-inflammatory agents with the development of coronary artery disease (CAD), especially tumor necrosis factor alpha, interleukins, and C-reactive protein. These inflammatory agents increase the production of reactive oxygen species (ROS), of which people with diabetes are known to have an increased production. The increase in ROS promotes lipid peroxidation, which causes damage to myocytes, promoting myocardial damage. Furthermore, oxidative stress induces the binding of NML to its receptor RAGE, which in turn activates the nuclear factor-kB, and conse-quently, inflammatory cytokines. These inflammatory cytokines induce endo-thelial dysfunction, with increased expression of adhesion molecules, changes in endothelial permeability and changes in the expression of nitric oxide. In this sense, the therapeutic use of monoclonal antibodies (inflammatory reducers such as statins and sodium-glucose transport inhibitors) has demonstrated positive results in the regression of atherogenic plaques and consequently CAD. On the other hand, many studies have demonstrated a relationship between mito-chondrial dynamics, diabetes, and cardiovascular diseases. This link occurs since ROS have their origin in the imbalance in glucose metabolism that occurs in the mitochondrial matrix, and this imbalance can have its origin in inadequate diet as well as some pathologies. Photobiomodulation (PBM) has recently been considered a possible therapeutic agent for cardiovascular diseases due to its effects on mitochondrial dynamics and oxidative stress. In this sense, therapies such as PBM that act on pro-inflammatory mediators and mitochondrial modulation could benefit those with cardiovascular diseases.

Keywords: Coronary artery disease; Diabetes; Mitochondrial dynamics; Nε-carboxymethyl-lysine; Oxidative stress.

Figure 1

Activation of nuclear factor kappa B by reactive oxygen species modulates inflammatory responses. Illustrative scheme demonstrating the activation of the nuclear factor kappa B transcription factor by reactive oxygen species and its modulation in inflammatory responses in vascular smooth muscle cells, endothelial cells, and macrophages. FIS: Fission protein; MFN: Mitofusins; NO: Nitric oxide; PBM: Photobiomodulation; ROS: Reactive oxygen species; NF-κB: Nuclear factor-kappa B.