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Published on: October 17, 2017
Malondialdehyde-modified low density lipoproteins in patients with atherosclerotic disease
1Center for Molecular and Vascular Biology, University of Leuven, Belgium.
Abstract:
The murine monoclonal antibody mAb-1H11 raised against malondialdehyde (MDA)-modified LDL, was used to detect cross-reacting material in human atheromatous tissue and in plasma. MDA-modified LDL levels in plasma were 0.19 +/- 0.02 mg/dl (mean +/- SEM) in 44 control subjects, 0.24 +/- 0.02 mg/dl in 15 patients with chronic stable angina pectoris (P = NS vs LDL cholesterol matched controls), 1.4 +/- 0.1 mg/dl in 60 patients with acute myocardial infarction (P < 0.001 vs controls), and 0.86 +/- 0.11 mg/dl in 22 patients with carotid atherosclerosis (P < 0.001 vs controls). Modified LDL, isolated from pooled LDL of 10 patients, showed a higher electrophoretic mobility on agarose gels, a higher content of thiobarbituric acid reactive substances, and a higher cholesterol/protein ratio than native LDL and had a similar reactivity (antigen/protein ratio) in the assay as the in vitro MDA-modified LDL used for calibration. Its apo B-100 moiety was not fragmented. Uptake of this modified LDL by macrophages resulted in foam cell generation. In conclusion, elevated plasma levels of atherogenic MDA-modified LDL may be a marker for unstable atherosclerotic cardiovascular disease.
Insights
Elevated levels of malondialdehyde-modified LDL (MDA-LDL) in plasma are linked to unstable atherosclerotic cardiovascular disease. This finding suggests MDA-LDL may serve as a valuable biomarker for disease progression.
Area of Science:
- Cardiovascular Science
- Immunology
- Biochemistry
Background:
- Atherosclerosis involves the modification of low-density lipoprotein (LDL).
- Malondialdehyde (MDA)-modified LDL is a specific form of modified LDL implicated in atherogenesis.
- Detecting MDA-modified LDL could aid in assessing cardiovascular disease risk.
Purpose of the Study:
- To investigate the presence and levels of MDA-modified LDL in human plasma.
- To evaluate MDA-modified LDL as a potential biomarker for atherosclerotic cardiovascular disease.
Main Methods:
- Development and use of a murine monoclonal antibody (mAb-1H11) against MDA-modified LDL.
- Quantification of plasma MDA-modified LDL levels in control subjects and patients with cardiovascular conditions.
- Characterization of isolated modified LDL properties (electrophoretic mobility, thiobarbituric acid reactive substances, cholesterol/protein ratio).
- Assessment of modified LDL uptake by macrophages and foam cell formation.
Main Results:
- Plasma MDA-modified LDL levels were significantly elevated in patients with acute myocardial infarction (1.4 mg/dl) and carotid atherosclerosis (0.86 mg/dl) compared to controls (0.19 mg/dl).
- Levels were not significantly different in patients with chronic stable angina.
- Isolated modified LDL exhibited altered biochemical properties and induced foam cell generation in macrophages.
- The apo B-100 moiety of modified LDL remained intact.
Conclusions:
- Elevated plasma levels of atherogenic MDA-modified LDL are associated with acute myocardial infarction and carotid atherosclerosis.
- MDA-modified LDL may serve as a biomarker for unstable atherosclerotic cardiovascular disease.
- Further research is warranted to explore its clinical utility.
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