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Modified LDL Immune Complexes and Cardiovascular Disease.

Maria F Lopes-Virella1, Gabriel Virella2

  • 1Department of Medicine, Medical University of South Carolina, Charleston, SC, USA; Ralph A. Johnson VA Medical Center, Charleston, SC, United States.

Current Medicinal Chemistry
|May 25, 2018
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Summary

Immune complexes (IC) involving modified LDL predict cardiovascular disease (CVD). Different LDL modifications within ICs, like oxidized LDL (oxLDL) and malondialdehyde LDL (MDA-LDL), influence atherosclerosis progression and acute vascular event risk.

Keywords:
LDL-immune complexesMDA-LDLModified LDLapoptosislabile plaquesoxLDLvascular inflammation.

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Area of Science:

  • Cardiovascular immunology
  • Atherosclerosis research
  • Lipid metabolism and disease

Background:

  • Modified low-density lipoprotein (LDL) forms are immunogenic, leading to the formation of antigen-antibody complexes (immune complexes, IC).
  • Circulating IC levels are established predictors of cardiovascular disease (CVD).
  • The specific antigenic composition of ICs can modulate CVD development.

Purpose of the Study:

  • To analyze the constitution of circulating immune complexes.
  • To investigate the differential impact of various LDL modifications within ICs on cardiovascular disease progression and risk.
  • To elucidate the in vitro mechanisms by which different IC types affect vascular cells and plaque stability.

Main Methods:

  • Measurement of circulating immune complexes (IC) in peripheral blood.
  • Generation of antibodies recognizing specific LDL modifications (e.g., copper oxidized LDL (oxLDL), malondialdehyde LDL (MDA-LDL)).
  • In vitro studies assessing the effects of oxLDL IC and MDA-LDL IC on cell proliferation, macrophage apoptosis, matrix metalloproteinase (MMP) release, and tumor necrosis factor (TNF) levels.

Main Results:

  • Patients with ICs strongly reacting with oxLDL antibodies show increased atherosclerosis markers (intima-media thickness, coronary calcification).
  • Patients with ICs strongly reacting with MDA-LDL antibodies face a high risk of acute vascular events, particularly myocardial infarction.
  • MDA-LDL ICs induce greater macrophage apoptosis and higher MMP/TNF release compared to oxLDL ICs, contributing to plaque vulnerability.

Conclusions:

  • The antigenic composition of LDL-containing immune complexes significantly influences cardiovascular disease outcomes.
  • MDA-LDL ICs are associated with acute vascular events through mechanisms promoting plaque instability (apoptosis, fibrous cap thinning).
  • Targeting specific IC components may offer novel strategies for managing CVD risk.