Proinflammatory monocyte polarization in type 2 diabetes mellitus and coronary heart disease

Abstract

How to cite this article: Nikiforov NG, Galstyan KO, Nedosugova LV, Elizova NV, Kolmychkova KI, Ivanova EA. Proinflammatory monocyte polarization in type 2 diabetes mellitus and coronary heart disease. Vessel Plus 2017;1:192-5.Aim: Type 2 diabetes mellitus (T2DM) is associated with rapid progression of atherosclerosis. There is no doubt that inflammation is involved in atherogenesis. Recent studies showed the relationship between the development of atherosclerotic plaque formation and the amount of pro-inflammatory (M1) activated macrophages in situ. Methods: The authors studied the ability of circulating monocytes isolated from patients with diabetes (n = 28), coronary heart disease (CHD) (n = 27) and healthy subjects (n = 50) to be activated into M1 phenotype in vitro. Results: Increased levels of basal and stimulated secretion of tumor necrosis factor alpha (TNF-α) was observed in diabetic patients compared with healthy subjects. On the contrary, in patients with CHD, decreased secretion of the pro-inflammatory cytokine, TNF-α, was found. A direct correlation between glycated hemoglobin (HbA1c) levels in T2DM patients and basal secretion of TNF-α from monocytes was observed. Conclusion: The authors found diametrically different responses of monocytes from T2DM and CHD under pro-inflammatory stimuli. Key words:Type 2 diabetes mellitus, coronary heart disease, M1/M2 monocyte polarization, oxidative stress, atherosclerosis, inflammatory ABSTRACTArticle history:

Modification of Tumor Necrosis Factor-α and C-C Motif Chemokine Ligand 18 Secretion by Monocytes Derived from Patients with Diabetic Foot Syndrome

“…According to our previous studies, in patients with newly diagnosed diabetes mellitus who did not receive hypoglycemic therapy there was a significant increased stimulated pro-inflammatory and anti-inflammatory activation of blood-delivered monocytes in comparison with healthy donors [22]. When assessing the activation of monocytes from patients with newly diagnosed T2DM, we have found a more pronounced stimulated pro-and anti-inflammatory response compared to the patients with a long history of the disease.…”

“…Data from patients from different groups were included in each series of cell isolation and cultivation, as well as measurements of cytokine secretion. In the current study we did not include a previously published comparative analysis of the activation abilities of monocytes isolated from the blood of healthy donors and T2DM patients, limited only by comparison of patients with T2DM with and without DFS [22]. Monocytes were derived from peripheral blood of patients using centrifugation with the density gradient of Ficoll followed by magnetic separation of CD14+ cells (Miltenyi Biotech, USA).…”

Monocyte differentiation and macrophage polarization

“…Induction of Nrf2 in response to oxidative stress has a cytoprotective and cardioprotective effect since this factor is involved in the generation of anti-atherogenic macrophage subsets that are involved in hemoglobin/heme/iron utilization and recycling thereby decreasing the intraplaque oxidative stress and damage [162] . However, in the microenvironment rich in oxidative low-density lipoprotein and pro-inflammatory cytokines, Nrf2 up-regulation may have pro-atherosclerotic consequences because it stimulates expression of several iron-metabolizing genes such as HO-1, ferroportin, ferritin, and hepcidin that increases iron trapping and oxidative stress in macrophages, enhances lipid accumulation and formation of foam cells [163,164] .…”

Subcellular anti-atherosclerotic therapy

“…In addition to 5-ALA, there are many other mitochondria targeting substances. This is a good arsenal for a broad search for potential drugs for subcellular therapy including anti-atherosclerotic therapy [4,5] .…”