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

  • M. V. BilenkoEmail author
  • A. V. Khilchenko
  • N. A. Nikitina
  • D. V. Aksenov
Experimental Studies

Abstract

The main goal of this study was to test our hypothesis that monocyte-derived macrophages of patients with ischemic heart disease (IHD, MPIHD) are in vivo prestimulated (primed) or stimulated cells. Their capacity for LDL oxidation and uptake exceeds that of macrophages from healthy donors (MPN). Monocytes were isolated from blood of 18 healthy donors and 25 IHD patients and LDL preparations were obtained from plasma of 16 healthy donors (LDLN) and 15 patients with familial hypercholesterolemia (LDLH). Aerobic incubation of LDLN or LDLH with MPIHD resulted in earlier accumulation (by 1 h) of TBARS in LDL, earlier aggregation of LDL (1 h vs 3 h in the case of MPN), 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 MPN (p < 0.01). MPIHD and MPN exhibited more effective oxidation and uptake of LDLH than LDLN 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 MPIHD 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.

Key words

monocyte-derived macrophages LDL ischemic heart disease hypercholesterolemia lipid peroxidation atherosclerosis hypoxia 

Abbreviations

EPM

absolute electrophoretic mobility

IHD

ischemic heart disease

LDL

lowdensity lipoproteins

LDLH

LDL from the blood plasma of hypercholesterolemic patients

LDLN

LDL from blood plasma of healthy donors

LPO

lipid peroxidation

MDA

malondialdehyde

MIF

macrophage migration inhibiting factor

MPIHD

macrophages from IHD patients

MPN

macrophages from healthy donors

oXLDL

oxidized LDL

REM

relative electrophoretic mobility

ROS

reactive oxygen species

SDS-PAAG

SDS-PAAG sodium dodecyl sulfatepolyacrylamide gel

SDS-PAGE

sodium dodecyl sulfate polyacrylamide gel electrophoresis

TBARS

thiobarbituric acid-reactive substances

TCh

total cholesterol

TNF-α

tumor necrosis factor alpha

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Copyright information

© MAIK Nauka 2008

Authors and Affiliations

  • M. V. Bilenko
    • 1
    Email author
  • A. V. Khilchenko
    • 1
  • N. A. Nikitina
    • 1
  • D. V. Aksenov
    • 2
  1. 1.Orekhovich Institute of Biomedical ChemistryRussian Academy of Medical SciencesMoscowRussia
  2. 2.Research Institute of Experimental CardiologyMinistry of Public Health and Social Development of the Russian FederationMoscowRussia

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