Elevated CD14 ++ CD16 − Monocytes Predict Cardiovascular Events
Abstract
Background—: Although monocytes in peripheral blood are no longer considered to be a homogeneous population, associations between distinct monocyte subsets and cardiovascular disease have not been highlighted in large epidemiological studies. Methods and Results—: The study included 700 randomly selected subjects from the cardiovascular arm of the Malmö Diet and Cancer study. Among these, 123 subjects experienced ischemic cardiovascular events during the follow-up until December 2008. Mononuclear leukocytes frozen at the baseline investigation in 1991 to 1994 were thawed and analyzed with flow cytometry to enumerate monocyte subsets, based on CD14 and CD16 expression. The percentage and number of classical CD14 ++ CD16 − monocytes were increased in the cardiovascular-event group compared with the event-free subjects (median, 69% [interquartile range, 62% to 76%] versus 67% [59% to 72%], P =0.017; 344 [251 to 419] cells/μL versus 297 [212 to 384] cells/μL, P =0.003). The hazard ratio was 1.66 for suffering a cardiovascular event in the highest tertile of the number of CD14 ++ CD16 − monocytes compared with the lowest tertile, even after adjustment for common risk factors (HR, 1.66; 95% CI: 1.02 to 2.72). CD14 ++ CD16 − monocytes did not, however, associate with the extent of atherosclerosis at baseline. In contrast, the percentage of monocytes expressing CD16 was negatively associated to the extent of carotid atherosclerosis measured as intima-media thickness at baseline. The chemokine receptors CCR2, CX3CR1, and CCR5 were not differentially expressed between cases and controls on any of the monocyte subsets, but CCR5 expression on CD14 + CD16 ++ monocytes was negatively associated to carotid intima-media thickness. Conclusions—: This study shows that classical CD14 ++ CD16 − monocytes can predict future cardiovascular risk independently of other risk factors in a randomly selected population.
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Modified lipids activate intimal inflammatory cells to secrete pro-inflammatory chemokines and cytokines, promoting further recruitment of myeloid inflammatory cells, particularly inflammatory monocytes, in mice and humans.
“The modified lipids then activate the inflammatory cells present in the intima, which respond by secreting pro-inflammatory chemokines and cytokines that in turn activate circulating leukocytes and the local endothelial cells, thereby promoting further recruitment of inflammatory cells of myeloid origin, particularly a specific subset of circulating monocytes with inflammatory potential, as shown”
From Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities (2019) · cites this paper as [19]
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- Authors
- Berg, K. E., Ljungcrantz, I., Andersson, L., Bryngelsson, C., Hedblad, B., Fredrikson, G. N., Nilsson, J., & Björkbacka, H.
- Affiliations
- Malmö University (SE)
- Venue
- Circulation: Cardiovascular Genetics
- Published
- 2012-02
- Volume
- 5
- Issue
- 1
- Pages
- 122-131
- ISSN
- 1942-325X (ISSN-L)
- 1942-3268
- OpenAlex
- W2165073428
- Cited by
- 257
- References
- 42
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 16 · 2023: 18 · 2022: 12 · 2021: 20 · 2020: 23 · 2019: 22 · 2018: 19 · 2017: 16 · 2016: 24 · 2015: 14 · 2014: 18 · 2013: 18 · 2012: 11
- FWCI
- 8.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation Cardiovascular Genetics (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Malmö University Publications (Malmö University) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Oncology › Inflammatory Biomarkers in Disease Prognosis
- Keywords
- CD14+CD16+ monocytes, classical monocytes, monocyte subsets, cardiovascular risk prediction, ischemic cardiovascular events, carotid intima-media thickness, atherosclerosis, CCR5, CCR2, CX3CR1, chemokine receptors, Malmö Diet and Cancer Study
- MeSH terms
- CX3C Chemokine Receptor 1, Aged, Cardiovascular Diseases, Female, Follow-Up Studies, Humans, Male, Middle Aged, Monocytes, Phenotype, Predictive Value of Tests, Risk Factors, Proportional Hazards Models, Receptors, IgG, Disease-Free Survival, Lipopolysaccharide Receptors, Receptors, Chemokine, Receptors, CCR5, Receptors, CCR2
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