LDL oxidation and uptake by monocyte-derived macrophages from the blood of patients with ischemic heart disease

Bilenko M.V.1 , Khilchenko A.V.1, Nikitina N.A.1, Aksenov D.V.2

1. Orekhovich Institute of Biomedical Chemistry, Russian Academy of Medical Sciences
2. Institute of Experimental Cardiology, Ministry of Public Health and Social Development of the Russian Federation
Section: Experimental/Clinical Study
PubMed Id: 18712088
Year: 2008  Volume: 54  Issue: 3  Pages: 322-340
The aim of this study was to test our hypothesis that monocyte-derived macrophages of patients with ischemic heart diseases (IHD, MPIHD) were prestimulated (primed) or stimulated cells whose capacity for LDL oxidation and uptake exceeded that of macrophages from healthy donors (MPN). Monocytes were obtained from the blood of 18 healthy donors and 25 IHD patients; plasma LDL - from 16 another group healthy donors (LDLN) and 15 patients with family hypercholesterolemia. Incubation of LDLN or LDLH with MPIHD or MPN was carried out under aerobic and hypoxic conditions. It was shown that incubation of LDLN or LDLH with MPIHD TBARS accumulation, LDL aggregation, apoB fragmentation were observed earlier and proceeded more actively than in the case of incubation with MPN. MPIHD (compared to MPN) more actively uptook LDLH and LDLN as accumulated greater amounts of total cholesterol (TCh) (by a factor of 1.8-2.1; p < 0.05-0.01), and their viability decreased to a markedly greater degree (p < 0.01). MPIHD and MPN also oxidized and took up LDLH with a higher intensity than LDLN, and their capacity for LDL oxidation and uptake increased, under hypoxic condition, compared to those under aerobic conditions. Thus, new experimental results provide direct evidence that macrophages of IHD patients are in vivo priming or stimulated cells and that this stimulation, especially in combination with hypercholesterolemic LDL and hypoxia, is a very strong risk factor that can predispose these patients to the onset or progression of atherosclerosis. Using MPIHD, it was created express-method for evaluation the degree of monocyte/macrophage stimulation in patients with IHD, selection of premedication medicine and new antiatherosclerotic and antiischemic drugs.
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Keywords: monocyte-derived macrophages, low density lipoproteins, ischemic heart disease, hypercholesterolemia, lipid peroxidation, atherosclerosis, hypoxia

Bilenko, M. V., Khilchenko, A. V., Nikitina, N. A., Aksenov, D. V. (2008). LDL oxidation and uptake by monocyte-derived macrophages from the blood of patients with ischemic heart disease. Biomeditsinskaya Khimiya, 54(3), 322-340.
This paper is also available as the English translation: 10.1134/S1990750808040100
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