Oxidation and uptake of LDL by monocyte-derived macrophages from blood of patients with IHD

The main goal of this study was to test our hypothesis that monocyte-derived macrophages of patients with ischemic heart disease (IHD, MP IHD ) are in vivo prestimulated (primed) or stimulated cells. Their capacity for LDL oxidation and uptake exceeds that of macrophages from healthy donors (MP N )....

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Published in:Biochemistry (Moscow). Supplement. Series B, Biomedical chemistry Biomedical chemistry, 2008-12, Vol.2 (4), p.393-405
Main Authors: Bilenko, M. V., Khilchenko, A. V., Nikitina, N. A., Aksenov, D. V.
Format: Article
Language:English
Subjects:
Biochemistry
Bioorganic Chemistry
Cardiovascular disease
Chemistry
Chemistry and Materials Science
Cholesterol
Experimental Studies
Hypoxia
Lipids
Medicinal Chemistry
Oxidation
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Summary:The main goal of this study was to test our hypothesis that monocyte-derived macrophages of patients with ischemic heart disease (IHD, MP IHD ) are in vivo prestimulated (primed) or stimulated cells. Their capacity for LDL oxidation and uptake exceeds that of macrophages from healthy donors (MP N ). Monocytes were isolated from blood of 18 healthy donors and 25 IHD patients and LDL preparations were obtained from plasma of 16 healthy donors (LDL N ) and 15 patients with familial hypercholesterolemia (LDL H ). Aerobic incubation of LDL N or LDL H with MP IHD resulted in earlier accumulation (by 1 h) of TBARS in LDL, earlier aggregation of LDL (1 h vs 3 h in the case of MP N ), more pronounced LDL apoB fragmentation as well as increased LDL uptake with the increase in accumulation of total cholesterol (TCh; by 1.8–2.1-fold, p < 0.05–0.01) and the decrease in cell viability compared with MP N ( p < 0.01). MP IHD and MP N exhibited more effective oxidation and uptake of LDL H than LDL N and in most tests this capacity (to oxidize and uptake LDL) increased under hypoxic conditions. These results demonstrate that macrophages of IHD patients are in vivo stimulated cells and that this stimulation, especially in combination with hypercholesterolemic LDL and local or generalized hypoxia, represent serious predisposition for onset or progression of atherosclerosis in IHD patients. The express test model based on MP IHD may be used for estimation of monocyte/macrophage stimulation in IHD patients as well as for optimization of drug therapy and screening new antiatherosclerotic and antiischemic drugs.
ISSN:1990-7508
1990-7516
DOI:10.1134/S1990750808040100