Increased intermediate CD14++CD16++ monocyte subset levels associate with restenosis after peripheral percutaneous transluminal angioplasty

Wildgruber, Moritz; Czubba, Maria; Aschenbrenner, Teresa; Wendorff, Heiko; Hapfelmeier, Alexander; Glinzer, Almut; Schiemann, Matthias; Zimmermann, Alexander; Eckstein, Hans‐Henning; Berger, Hermann; Wohlgemuth, Walter A.; Meier, Reinhard; Libby, Peter; Zernecke, Alma

doi:10.1016/j.atherosclerosis.2016.09.002

Cited by 23 publications

(22 citation statements)

References 38 publications

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“…Moreover, CD14 ++ CD16 + monocytes secrete high levels of tumor necrosis factor-α and interleukin-1β, which are involved in the pathogenesis and progression of atherosclerosis [3, 24]. Alternatively, myeloperoxidase expression may be involved.…”

Section: Discussionmentioning

confidence: 99%

“…Alternatively, myeloperoxidase expression may be involved. CD14 ++ CD16 + monocytes have been shown to have high levels of intracellular myeloperoxidase expression [21, 24], which is associated with atherosclerotic plaque progression and rupture [25, 26]. Furthermore, high levels of myeloperoxidase promote endothelial cell death, activate matrix metalloproteinases, and are a predictor of plaque vulnerability [27, 28].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Impact of CD14++CD16+ monocytes on plaque vulnerability in diabetic and non-diabetic patients with asymptomatic coronary artery disease: a cross-sectional study

Yoshida

Yamamoto

Shinke

et al. 2017

Cardiovasc Diabetol

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BackgroundPreviously, we have reported that daily glucose fluctuations could affect coronary plaque vulnerability, but the underlying mechanisms remained unclear. This study sought to investigate the impact of CD14++CD16+ monocytes on plaque vulnerability, as assessed by virtual histology intravascular ultrasound (VH-IVUS), as well as their relationship to fluctuating glucose levels in patients with asymptomatic coronary artery disease (CAD).MethodsFifty-one patients with asymptomatic CAD, who were undergoing lipid-lowering therapy and underwent VH-IVUS evaluation for angiographically mild to moderate lesions, were enrolled in the study. Standard VH-IVUS parameters, including the percentage volume of the necrotic core (%NC) within the plaque and the presence of a virtual histology thin-cap fibroatheroma (VH-TCFA), were then evaluated. Additionally, monocyte subsets were assessed by flow cytometry, and daily glucose fluctuations were analyzed by measuring the mean amplitude of glycemic excursion (MAGE).ResultsAmong 82 plaques from 22 diabetes mellitus (DM) patients and 29 non-DM patients, 15 VH-TCFAs were identified. CD14++CD16+ monocyte counts significantly correlated with both %NC and the presence of VH-TCFA (%NC: r = 0.339, p = 0.002; VH-TCFA: p = 0.003). Multivariate logistic regression analysis revealed that CD14++CD16+ monocyte counts were independently associated with VH-TCFA (odds ratio = 1.029, p = 0.004). Furthermore, CD14++CD16+ monocyte counts were significantly correlated with the MAGE score in the non-DM patients (r = 0.544, p = 0.005).ConclusionsCD14++CD16+ monocyte levels are associated with coronary plaque vulnerability and can serve as a biomarker for VH-TCFA in patients with CAD undergoing lipid-lowering therapy. In patients without DM, glucose fluctuations may alter the balance of monocyte subsets. Trial registration UMIN Registry number: UMIN000021228Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-017-0577-8) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Impact of CD14++CD16+ monocytes on plaque vulnerability in diabetic and non-diabetic patients with asymptomatic coronary artery disease: a cross-sectional study

Yoshida

Yamamoto

Shinke

et al. 2017

Cardiovasc Diabetol

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“…During the last years, multiple studies have been published regarding a certain expansion or contraction of a single subpopulation with diseases like lupus, rheumatoid arthritis, atherosclerosis or membranous glomerulonephritis (5-7), among others. Even when intermediate subpopulation tends to show expansion in some inflammatory conditions, these results are not consistent between different publications and usually are just mildly significant (8).…”

Section: Introductionmentioning

confidence: 61%

“…In atherosclerosis and its complications like myocardial infarction and stroke, it has been found by some studies that the intermediate subpopulation of monocytes evidently expands (8), but in others only a reduction in classical monocytes without significant changes in intermediate or non-classical monocyte subsets (9). Many studies have covered this point without agreement, showing, until now, conflicting evidence of measurable changes in cell frequencies in clinical settings (10).…”

Section: Introductionmentioning

confidence: 99%

Pro-inflammatory response of non-inflammatory Classical monocytes stimulated with LPSin vitro

Karsulovic

Tempio

Lopez

et al. 2020

Preprint

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15 BACKGROUND: CD14 (Monocyte identifying Toll-Like Receptor) and CD16 (FcyRIII co-receptor, marker of 16 inflammatory monocytes) were used to define 3 subpopulations of circulating monocytes with different attributes in terms 17 of inflammatory and phagocytic capabilities. There are contradictory reports regarding response of circulating monocytes 18 to pro-inflammatory or non-inflammatory stimuli in vitro. Here we aimed to analyze the phenotypic changes in 19 circulating monocytes when stimulated with pro and non-inflammatory stimuli. 20 METHODS: Whole blood from 9 healthy donors was extracted and studied. Monocyte subpopulations were directly 21 measured using flow cytometry with PBMC Ficoll extraction method. Pro-inflammatory interleukin IL-1β was measured 22 by intracellular cytometry. Whole blood-extracted monocytes were stimulated using LPS and IL-4 as previously 23 described. Changes against non-stimulated (N-S) populations were statistically analyzed. 24 RESULTS: Compared to N-S, LPS-stimulated monocytes display a singular milieu of markers, with higher levels of 25 intracellular IL-1β in parallel raise of CD14+CD163-/CD14+CD163+ ratio. CD163 shows positive correlation with levels 26 of IL-1β. In t-SNE (T-distributed Stochastic Neighbor Embedding) analysis, after LPS stimulation, subpopulation 27 CD14+CD16-CD163-, containing mainly classical monocytes, show a higher number of IL-1β+ cells.28 CONCLUSION: Classical monocytes, the non-inflammatory subset, show higher levels of IL-1β in response to LPS 29 narrowing down to a new subpopulation of monocytes CD14+CD16-CD163-, which correlates better with this interleukin 30 response than widely used monocytes classification. Using CD163 in addition to CD16, we were able to show that 31 classical monocytes display the most intense response to LPS. Additionally, CD163 appears to be a suitable addition to 32 CD14-CD16 classification to improve its performance. 33

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“…Several studies have demonstrated a significant association between monocyte subsets and atherosclerosis plaque severity, vulnerability, and progression of CVD 7,8,[14][15][16][17] . Additionally, CD14 CD16 monocytes were associated with restenosis, after percutaneous transluminal angioplasty, in individuals with peripheral artery disease 18) .…”

Section: Discussionmentioning

confidence: 96%

Relationship between Circulating Inflammatory Monocytes and Cardiovascular Disease Measures of Carotid Intimal Thickness

SahBandar

Ndhlovu

Saiki

et al. 2020

JAT

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The official journal of the Japan Atherosclerosis Society and the Asian Pacific Society of Atherosclerosis and Vascular Diseases Original Article Aims: Cardiovascular disease (CVD) remains the leading cause of death worldwide despite improvements in the treatment of atherosclerosis, an inflammatory disease and major underlying cause of CVD. Monocytes, an innate immune cell type, are linked to CVD progression; however, given their heterogeneity, the association between distinct monocyte subsets and increased risk of CVD remains unclear. This study investigated the association between peripheral monocyte subpopulation numbers and carotid intima-media thickness (cIMT), a sensitive measure of CVD risk, in a cohort of adults recruited from the general population. Methods: We used clinical data and peripheral blood mononuclear cell (PBMC) specimens from 67 individuals. cIMT was measured by high-resolution, B-mode, ultrasound images of the right carotid artery. PBMCs were stained with conjugated monoclonal antibodies to define monocyte subpopulations based on CD14 and CD16 co-expressions into classical (CD14 CD16), intermediate/inflammatory (CD14 CD16), and non-classical/ patrolling (CD14 low/ CD16) monocytes. Results: We found a higher intermediate monocyte count was significantly correlated with increased right common carotid artery (RCCA) and right carotid bifurcation (RBIF) intima-media thickness (IMT) (p 0.004 and 0.006, respectively), even after adjusting for CVD-associated clinical data (p 0.006 and 0.004, respectively). Conclusion: Our study demonstrated a strong correlation between inflammatory monocyte counts and cIMT. These results suggest that, in the general population, there is a relationship between intermediate monocyte expansion and elevated predictors for CVD risk, and intermediate monocytes may be involved in the development of atherosclerosis and metabolic diseases. Strategies targeting inflammatory monocytes may be needed to slow CVD progression. role in atherosclerotic plaque formation 1, 3). Based on CD14 and CD16 surface co-expression, monocytes are classified into three different subsets: classical (CD14 CD16), intermediate or inflammatory (CD14 CD16), and non-classical or patrolling (CD14 low/ CD16) 4). Existing studies have demonstrated monocytes' roles in various disorders, including those that are associated with CVD. Higher levels of classical monocytes have been correlated with insulin resistance, a metabolic disorder closely related to

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Increased intermediate CD14++CD16++ monocyte subset levels associate with restenosis after peripheral percutaneous transluminal angioplasty

Cited by 23 publications

References 38 publications

Impact of CD14++CD16+ monocytes on plaque vulnerability in diabetic and non-diabetic patients with asymptomatic coronary artery disease: a cross-sectional study

Impact of CD14++CD16+ monocytes on plaque vulnerability in diabetic and non-diabetic patients with asymptomatic coronary artery disease: a cross-sectional study

Pro-inflammatory response of non-inflammatory Classical monocytes stimulated with LPSin vitro

Relationship between Circulating Inflammatory Monocytes and Cardiovascular Disease Measures of Carotid Intimal Thickness

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