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Updated: Jan 17, 2026
Quantification of Monocyte Transmigration and Foam Cell Formation from Individuals with Chronic Inflammatory Conditions
Published on: October 17, 2017
Human monocyte inflammation in patients with Lp(a) or atherosclerotic cardiovascular disease is not accompanied by
Rosalie W M Kempkes1, Jordan M Kraaijenhof2, Bram W van Os1
1Department of Medical Biochemistry, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands (Kempkes, Dr van Os, Griffith, Drs Lutgens, Prange, de Winther, and Neele); Amsterdam Cardiovascular Sciences (ACS), Atherosclerosis & Ischemic Syndromes, Amsterdam UMC, The Netherlands (Kempkes, Dr Kraaijenhof, Dr van Os, Dr Kaiser, Dr Nurmohamed, Griffith, Drs Lutgens, Stroes, Prange, de Winther, Kroon, and Neele); Department of Inflammatory Diseases, Amsterdam Institute for Immunology and Infectious Diseases (AII), Amsterdam UMC, The Netherlands (Kempkes, Dr van Os, Griffith, Drs Prange, de Winther, and Neele).
Insights
High lipoprotein(a) [Lp(a)] levels increase monocyte inflammation but do not alter chromatin accessibility. This suggests Lp(a) and atherosclerotic cardiovascular disease (ASCVD) pro-inflammatory effects on monocytes are regulated epigenetically by other mechanisms.
Area of Science:
- Cardiovascular Science
- Immunology
- Epigenetics
Background:
- High plasma lipoprotein(a) [Lp(a)] levels accelerate atherosclerosis and atherosclerotic cardiovascular disease (ASCVD).
- Monocytes play a key role in ASCVD pathogenesis and inflammation.
- Epigenetic modifications, such as chromatin accessibility, may regulate monocyte inflammatory responses.
Purpose of the Study:
- To investigate the impact of high Lp(a) on monocyte gene expression and chromatin accessibility.
- To explore the relationship between Lp(a) levels, ASCVD status, and monocyte inflammatory markers.
- To determine if chromatin accessibility differences underlie enhanced monocyte inflammation in high Lp(a) individuals.
Main Methods:
- Observational case-control study with 60 subjects stratified by Lp(a) levels (<25 nmol/L vs. >350 nmol/L) and ASCVD history.
- Analysis of gene expression and chromatin accessibility in classical monocytes using RT-qPCR and bulk ATAC-sequencing.
- Measurement of plasma cytokine levels, including CXCL10.
Main Results:
- Subjects with high Lp(a) exhibited increased IFIT3 gene expression and elevated plasma CXCL10 levels.
- No significant differences in monocyte chromatin accessibility were observed between high and low Lp(a) groups, regardless of ASCVD status.
- Findings suggest increased interferon-γ signaling in monocytes of individuals with elevated Lp(a).
Conclusions:
- Elevated Lp(a) is associated with enhanced monocyte inflammation and specific gene/cytokine profiles.
- Chromatin accessibility in monocytes does not appear to be the primary regulatory mechanism for Lp(a)-driven inflammation.
- Alternative epigenetic or non-epigenetic mechanisms likely mediate the pro-inflammatory effects of Lp(a) and ASCVD on monocytes.
Background And Aims:
High plasma lipoprotein(a) [Lp(a)] levels are associated with accelerated atherosclerosis and subsequent atherosclerotic cardiovascular disease (ASCVD), potentially through enhanced inflammatory signaling of monocytes. Given that monocytes are major players in ASCVD risk and the role of epigenetic changes in regulating their responsiveness, we propose that investigating changes in chromatin accessibility could reveal the underlying mechanisms of enhanced monocyte inflammation.
Methods:
In this observational case-control study, we collected blood from subjects with low (<25 nmol/L) and elevated (>350 nmol/L) plasma Lp(a) with and without a history of ASCVD, matched for age and sex. A total of 60 subjects were included in the study, comprising 60% males and a mean age of 62.8 ± 7.8 years. We assessed gene expression and chromatin accessibility of fluorescence-activated cell sorting (FACS)-sorted classical monocytes using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and bulk assay for transposase-accessible chromatin (ATAC)-sequencing and analyzed plasma cytokine levels.
Results:
Subjects with high plasma Lp(a) showed significantly increased gene expression of IFIT3. At the plasma level, subjects with high Lp(a) without ASCVD were distinguished by higher concentrations of chemokine C-X-C motif ligand 10 (CXCL10). While these results are consistent with previous research demonstrating increased interferon-γ signaling in monocytes of individuals with elevated Lp(a), we did not detect differences in chromatin accessibility of monocytes between subjects with high or low Lp(a), irrespective of ASCVD status.
Conclusion:
While subjects with high Lp(a) levels showed enhanced monocyte inflammation, no differences in chromatin accessibility were detected. This suggests that the pro-inflammatory signature of Lp(a) and ASCVD on monocytes is regulated at a level other than chromatin accessibility.
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