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Published on: October 17, 2017
Monocyte subset distribution in patients with stable atherosclerosis and elevated levels of lipoprotein(a)
Konstantin A Krychtiuk1, Stefan P Kastl2, Sebastian L Hofbauer2
1Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna, Austria.
Insights
Elevated lipoprotein(a) (Lp(a)) levels are linked to a proatherogenic shift in monocyte subsets, specifically increasing intermediate monocytes (IMs). This finding suggests a potential mechanism connecting Lp(a) to atherosclerosis progression.
Area of Science:
- Cardiovascular Science
- Immunology
- Lipidology
Background:
- Lipoprotein(a) (Lp(a)) is a known risk factor for atherosclerosis and thrombotic events.
- Lp(a) carries pro-inflammatory oxidized phospholipids (OxPL), contributing to vascular inflammation.
- Monocytes, key players in atherosclerosis, are classified into subsets with varying atherogenic potential.
Purpose of the Study:
- To investigate the association between elevated Lp(a) and OxPL/apoB levels and the distribution of monocyte subsets.
- To determine if Lp(a) influences the proportions of classical, intermediate, and nonclassical monocytes.
Main Methods:
- Study included 90 patients with stable coronary artery disease.
- Lp(a) and OxPL/apoB were quantified.
- Monocyte subsets (CM, IM, NCM) were identified using flow cytometry based on CD14 and CD16 expression.
Main Results:
- Patients with elevated Lp(a) (>50 mg/dL) showed a significantly higher proportion of intermediate monocytes (IMs).
- No significant differences were observed in classical (CM) or nonclassical (NCM) monocyte proportions.
- The association between Lp(a) and IMs was independent of traditional risk factors and inflammatory markers. OxPL/apoB levels correlated with IMs.
Conclusions:
- Elevated Lp(a) levels are associated with a proatherogenic monocyte subset distribution in patients with stable atherosclerotic disease.
- This suggests a potential mechanism linking Lp(a) to increased atherosclerosis risk via monocyte modulation.
Background:
Lipoprotein(a) (Lp(a)) is a proatherogenic plasma lipoprotein currently established as an independent risk factor for the development of atherosclerotic disease and as a predictor for acute thrombotic complications. In addition, Lp(a) is the major carrier of proinflammatory oxidized phospholipids (OxPL). Today, atherosclerosis is considered to be an inflammatory disease of the vessel wall in which monocytes and monocyte-derived macrophages are crucially involved. Circulating monocytes can be divided according to their surface expression pattern of CD14 and CD16 into at least 3 subsets with distinct inflammatory and atherogenic potential.
Objective:
The aim of this study was to examine whether elevated levels of Lp(a) and OxPL on apolipoprotein B-100-containing lipoproteins (OxPL/apoB) are associated with changes in monocyte subset distribution.
Methods:
We included 90 patients with stable coronary artery disease. Lp(a) and OxPL/apoB were measured, and monocyte subsets were identified as classical monocytes (CMs; CD14++CD16-), intermediate monocytes (IMs; CD14++CD16+), and nonclassical monocytes (NCMs; CD14+CD16++) by flow cytometry.
Results:
In patients with elevated levels of Lp(a) (>50 mg/dL), monocyte subset distribution was skewed toward an increase in the proportion of IM (7.0 ± 3.8% vs 5.2 ± 3.0%; P = .026), whereas CM (82.6 ± 6.5% vs 82.0 ± 6.8%; P = .73) and NCM (10.5 ± 5.3 vs 12.8 ± 6.0; P = .10) were not significantly different. This association was independent of clinical risk factors, choice of statin treatment regime, and inflammatory markers. In addition, OxPL/apoB was higher in patients with elevated Lp(a) and correlated with IM but not CM and NCM.
Conclusions:
In conclusion, we provide a potential link between elevated levels of Lp(a) and a proatherogenic distribution of monocyte subtypes in patients with stable atherosclerotic disease.
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