scholarly journals Nature versus Number: Monocytes in Cardiovascular Disease

2021 ◽  
Vol 22 (17) ◽  
pp. 9119
Author(s):  
Helen Williams ◽  
Corinne D. Mack ◽  
Stephen C. H. Li ◽  
John P. Fletcher ◽  
Heather J. Medbury
Keyword(s):  
Cardiovascular Disease ◽  
Atherosclerotic Plaque ◽  
Inflammatory Markers ◽  
Vessel Wall ◽  
Lipid Lowering ◽  
Disease Development ◽  
Monocyte Subsets ◽  
Plaque Development ◽  
And Function ◽  
Classical Monocytes

Monocytes play a key role in cardiovascular disease (CVD) as their influx into the vessel wall is necessary for the development of an atherosclerotic plaque. Monocytes are, however, heterogeneous differentiating from classical monocytes through the intermediate subset to the nonclassical subset. While it is recognized that the percentage of intermediate and nonclassical monocytes are higher in individuals with CVD, accompanying changes in inflammatory markers suggest a functional impact on disease development that goes beyond the increased proportion of these ‘inflammatory’ monocyte subsets. Furthermore, emerging evidence indicates that changes in monocyte proportion and function arise in dyslipidemia, with lipid lowering medication having some effect on reversing these changes. This review explores the nature and number of monocyte subsets in CVD addressing what they are, when they arise, the effect of lipid lowering treatment, and the possible implications for plaque development. Understanding these associations will deepen our understanding of the clinical significance of monocytes in CVD.

Circulating levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) are associated with monocyte subsets in patients with stable coronary artery disease

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
KA Krychtiuk ◽  
M Lenz ◽  
P Hohensinner ◽  
K Distelmaier ◽  
L Schrutka ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Stable Coronary Artery Disease ◽  
Statin Treatment ◽  
Lipid Lowering ◽  
Monocyte Subsets ◽  
Proprotein Convertase ◽  
Artery Disease ◽  
Circulating Levels ◽  
Classical Monocytes

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): FWF Background and aims Proprotein convertase subtilisin/kexin type-9 (PCSK9) is an enzyme promoting the degradation of low-density lipoprotein receptors (LDL-R) in hepatocytes. Inhibition of PCSK9 has emerged as a novel target for lipid-lowering therapy. Monocytes are crucially involved in the pathogenesis of atherosclerosis and can be divided into three subsets. The aim of this study was to examine whether circulating levels of PCSK9 are associated with monocyte subsets. Methods We included 69 patients with stable coronary artery disease. PCSK9 levels were measured and monocyte subsets were assessed by flow cytometry and divided into classical monocytes (CD14++CD16-; CM), intermediate monocytes (CD14++CD16+; IM) and non-classical monocytes (CD14 + CD16++; NCM). Results Mean age was 64 years and 80% of patients were male. Patients on statin treatment (n = 55) showed higher PCSK9-levels (245.4 (206.0-305.5) ng/mL) as opposed to those without statin treatment (186.1 (162.3-275.4) ng/mL; p = 0.05). In patients on statin treatment, CM correlated with circulating PCSK9 levels (R = 0.29; p = 0.04), while NCM showed an inverse correlation with PCSK9 levels (R=-0.33; p = 0.02). Patients with PCSK9 levels above the median showed a significantly higher proportion of CM as compared to patients with PCSK-9 below the median (83.5 IQR 79.2-86.7 vs. 80.4, IQR 76.5-85.2%; p = 0.05). Conversely, PCSK9 levels >median were associated with a significantly lower proportion of NCM as compared to those with PCSK9 <median (10.2, IQR 7.3-14.6 vs. 14.3, IQR 10.9-18.7%; p = 0.02). In contrast, IM showed no association with PCSK-9 levels. Conclusions We hereby provide a novel link between PCSK9 regulation, innate immunity and atherosclerotic disease in statin-treated patients.

Abstract 13272: High Density Lipoprotein Subclasses Predict Non-Cardiovascular Disease, Non-Cancer Chronic Inflammatory-Related Death and Hospitalization More Strongly than Cardiovascular Disease Events in the Multi-Ethnic Study of Atherosclerosis

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Daniel Duprez ◽  
James Otvos ◽  
Kenneth Feingold ◽  
Philip Greenland ◽  
Myron D Gross ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
High Density Lipoprotein ◽  
Inflammatory Markers ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipid Lowering ◽  
Ethnic Study ◽  
Lipoprotein Particles ◽  
D Dimer

In vitro studies have demonstrated that high density lipoprotein particles (HDL-P) antagonize inflammatory processes. We studied the predictive value of HDL-P and inflammatory markers for incident cardiovascular disease (CVD) and non-CVD, non-cancer, chronic inflammatory-related events. Methods: In the Multi-Ethnic Study of Atherosclerosis, we studied 6475 men and women free of overt CVD, baseline age 45-84 years, who had fasting venous samples for lipid profile, lipoprotein particles, and inflammatory markers Interleukin-6 (IL-6), hs-CRP and D-dimer at baseline. Median follow-up was 10.1 years. Poisson regression models predicted non-CVD, non-cancer, chronic inflammatory-related events (death and hospitalization), based on diagnostic codes, n=1054) and CVD events due to coronary heart disease, myocardial infarction, coronary artery disease requiring revascularization, stroke, peripheral arterial disease, congestive heart failure and CVD or unwitnessed death (adjudicated, n=756). Adjustment was for age, race, gender, clinic, heart rate, smoking, body mass index, blood pressure, blood pressure and lipid lowering medication, diabetes mellitus, plus all lipid, lipoprotein particle and inflammatory variables. Results: Non-CVD, non-cancer, chronic inflammatory-related events were inversely associated with the sum of small+medium HDL-P independent of covariates (relative risk (RR) per standard deviation (95% confidence limits), RR: 0.85 (0.79-0.91, P < 0.0001). Non-CVD, non-cancer, chronic inflammatory-related events were positively associated with IL-6, RR:1.19 (1.11-1.27, P < 0.0001) and D-dimer, RR: 1.10 (1.05-1.16, P < 0.0001). CVD was associated with small+medium HDL-P, RR: 0.90 (0.82-0.99, P < 0.03) and IL-6, RR:1.15 (1.06-1.25 P < 0.0001). hsCRP was unrelated to either outcome after adjustment for other inflammatory markers. Conclusion: The long-term inverse association of small+medium HDL-P with non-CVD, non-cancer, chronic inflammatory-related death and hospitalization was stronger than with fatal and non-fatal CVD in subjects initially free of overt CVD. These findings provide clinical evidence that small+medium HDL-P have anti-inflammatory properties and may rethink the importance of HDL-P beyond CVD.

scholarly journals Raman Spectroscopic Evaluation of the Effects of Diet and Lipid-Lowering Therapy on Atherosclerotic Plaque Development in Mice

2001 ◽  
Vol 21 (10) ◽  
pp. 1630-1635 ◽  
Author(s):  
Sweder W.E. van de Poll ◽  
Tjeerd J. Römer ◽  
Oscar L. Volger ◽  
Dianne J.M. Delsing ◽  
Tom C. Bakker Schut ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Raman Spectroscopic ◽  
Lowering Therapy ◽  
Plaque Development

The Effect of Plaque Morphology on Cap Stresses in Coronary Arteries

2012 ◽  
Author(s):  
A. C. Akyildiz ◽  
L. Speelman ◽  
H. Nieuwstadt ◽  
R. Virmani ◽  
J. Wentzel ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Sudden Death ◽  
Coronary Arteries ◽  
Atherosclerotic Plaque ◽  
Vessel Wall ◽  
Thrombus Formation ◽  
Plaque Formation ◽  
Plaque Morphology

Atherosclerosis is a cardiovascular disease characterized by plaque formation in the vessel wall. The region of an atherosclerotic plaque separating its pathological content from the lumen is called cap. Cap rupture initiates thrombus formation and may lead to myocardial infarction and sudden death [1].

Abstract 15930: Circulating Levels of Proprotein Convertase Subtilisin/kexin Type 9 (pcsk9) are Associated With Monocyte Subsets in Patients With Stable Coronary Artery Disease

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Konstantin Krychtiuk ◽  
Max Lenz ◽  
Philipp Hohensinner ◽  
Klaus Distelmaier ◽  
Lore Schrutka ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Stable Coronary Artery Disease ◽  
Statin Treatment ◽  
Lipid Lowering ◽  
Monocyte Subsets ◽  
Proprotein Convertase ◽  
Artery Disease ◽  
Circulating Levels ◽  
Classical Monocytes

Introduction: Proprotein convertase subtilisin/kexin type-9 (PCSK9) is an enzyme promoting the degradation of low-density lipoprotein receptors (LDL-R) in hepatocytes. Inhibition of PCSK9 has emerged as a novel target for lipid-lowering therapy. Monocytes are crucially involved in the pathogenesis of atherosclerosis. Circulating monocytes can be divided into three subsets. The aim of this study was to examine whether circulating levels of PCSK9 are associated with monocyte subsets. Methods: We included 69 patients with stable coronary artery disease. PCSK9 levels were measured and monocyte subsets were assessed by flow cytometry and divided into classical monocytes (CD14++CD16-; CM), intermediate monocytes (CD14++CD16+; IM) and non-classical monocytes (CD14+CD16++; NCM). Results: Mean age was 64 years and 80% of patients were male. Patients on statin treatment (n=55) showed higher PCSK9-levels (245.4 (206.0-305.5) ng/mL) as opposed to those without statin treatment (186.1 (162.3-275.4) ng/mL; p=0.05). In patients on statin treatment, CM correlated with circulating PCSK9 levels (R=0.29; p=0.04), while NCM showed an inverse correlation with PCSK9 levels (R=-0.33; p=0.02). Patients with PCSK9 levels above the median showed a significantly higher proportion of CM as compared to patients with PCSK-9 below the median (83.5 IQR 79.2-86.7 vs. 80.4, IQR 76.5-85.2%; p=0.05). Conversely, patients with PCSK9 levels >median were associated with a significantly lower proportion of NCM as compared to those with PCSK9 <median (10.2, IQR 7.3-14.6 vs. 14.3, IQR 10.9-18.7%; p=0.02). In contrast, IM showed no association with PCSK-9 levels. Conclusions: We hereby provide a novel link between PCSK9 regulation, innate immunity and atherosclerotic disease in statin-treated patients.

Abstract 13608: The Association Between Cardiometabolic Disorders/Cardiovascular Disease and the Distribution of Monocyte Subsets: A Systematic Review and Meta-Analysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ester Oh ◽  
Muzi Na ◽  
Connie Rogers
Keyword(s):  
Systematic Review ◽  
Cardiovascular Disease ◽  
Meta Analysis ◽  
Cochrane Central Register ◽  
Monocyte Subset ◽  
Healthy Controls ◽  
Monocyte Subsets ◽  
Cardiometabolic Disorders ◽  
Meta Analyses ◽  
Classical Monocytes

Introduction: Monocytes play a crucial role in the pathology of atherosclerosis, a major cause of cardiovascular disease (CVD). Previous studies in preclinical models report that monocyte subsets (i.e. classical, intermediate and non-classical monocytes) may differently contribute to the pathogenesis of atherosclerosis. However, changes in the distribution and the role of each monocyte subset in cardiometabolic disorders (overweight/obesity, metabolic syndrome, hypercholesterolemia, and type 2 diabetes) and CVD in humans is less clear. Therefore, the aim of the current systematic review and meta-analysis was to evaluate the association between the monocyte subset distribution and cardiometabolic disorders/CVD in humans. Methods: Articles were systematically searched in CINAHL, Cochrane Central Register of Controlled Trials, and PubMed until April 2020. A total of 1592 articles were independently screened by 2 reviewers. A total of 25 studies were selected for qualitative analyses. Among them, 6 studies reported the percentage of each monocyte subset and were included in the meta-analyses. For the meta-analyses, a random-effects model was used to generate pooled standardized mean differences (SMD) between subjects with cardiometabolic disorders and healthy controls. Results: In total, sample size ranged from 22 to 135, and mean age of subjects ranged from 22 to 70 years. The percentage of classical monocytes was lower [SMD = -1.21; 95% CI (-1.92, -0.50); P < 0.001; I 2 = 91%] in subjects with cardiometabolic disorders compared to healthy controls. However, the percentage of intermediate [SMD = 0.56; 95% CI (0.23, 0.88); P < 0.001; I 2 = 65%] and non-classical monocytes [SMD = 1.39; 95% CI (0.59, 2.19); P < 0.001; I 2 = 93%] was higher in subjects with cardiometabolic disorders compared to healthy controls. Conclusions: There may be a shift in the distribution of monocytes from classical to intermediate and non-classical monocytes in individuals with cardiometabolic disorders. This shift may be an underlying cause of chronic low-grade inflammation, exacerbate atherosclerotic risk, and contribute to the development of CVD based on preclinical studies. However, additional mechanistic studies are needed in humans to evaluate this question.

microRNA expression signatures and parallels between monocyte subsets and atherosclerotic plaque in humans

2012 ◽  
Vol 107 (04) ◽  
pp. 619-625 ◽  
Author(s):  
Bernd Denecke ◽  
André Rostalsky ◽  
Mihail Hristov ◽  
Thomas A. Koeppel ◽  
Kiril Bidzhekov ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Atherosclerotic Lesion ◽  
Vascular Diseases ◽  
Atherosclerotic Plaques ◽  
Monocyte Subset ◽  
Monocyte Subsets ◽  
Cardiovascular Biology ◽  
Classical Monocytes

SummarySmall non-coding microRNAs (miRNAs) have emerged to play critical roles in cardiovascular biology. Monocytes critically drive atherosclerotic lesion formation, and can be subdivided into a classical and non-classical subset. Here we scrutinised the miRNA signature of human classical and non-classical monocytes, and compared miRNA expression profiles of atherosclerotic plaques from human carotid arteries and healthy arteries. We identified miRNAs to be differentially regulated with a two-fold or higher difference between classical and non-classical monocyte subsets. Moreover, comparing miRNA expression in atherosclerotic plaques compared to healthy arteries, we observed several miRNAs to be aberrantly expressed, with the majority of miRNAs displaying a two-fold or higher increase in plaques and only few miRNAs being decreased. To elucidate similarities in miRNA signatures between monocyte subsets and atherosclerotic plaque, expression of miRNAs highly abundant in monocytes and plaque tissues were compared. Several miRNAs were found in atherosclerotic plaques but not in healthy vessels or either monocyte subset. However, we could identify miRNAs co-expressed in plaque tissue and classical monocytes (miR-99b, miR-152), or non-classical monocytes (miR-422a), or in both monocytes subsets. We thus unravelled candidate miRNAs, which may facilitate our understanding of monocyte recruitment and fate during atherosclerosis, and may serve as therapeutic targets for treating inflammatory vascular diseases.Note: The editorial process for this article was fully handled by Prof. G. Y. H. Lip, Editor-in-Chief.

IL-33 stimulates the release of procoagulant microvesicles from human monocytes and differentially increases tissue factor in human monocyte subsets

2017 ◽  
Vol 117 (07) ◽  
pp. 1379-1390 ◽  
Author(s):  
Stefan Stojkovic ◽  
Åsa Thulin ◽  
Lena Hell ◽  
Barbara Thaler ◽  
Sabine Rauscher ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Tissue Factor ◽  
Inflammatory Diseases ◽  
Human Monocyte ◽  
Receptor Expression ◽  
Human Monocytes ◽  
Monocyte Subsets ◽  
Prothrombotic State ◽  
St2 Receptor ◽  
Classical Monocytes

SummaryMonocytes and monocyte-derived microvesicles (MVs) are the main source of circulating tissue factor (TF). Increased monocyte TF expression and increased circulating levels of procoagulant MVs contribute to the formation of a prothrombotic state in patients with cardiovascular disease. Interleukin (IL)-33 is a pro-inflammatory cytokine involved in atherosclerosis and other inflammatory diseases, but its role in regulating thrombosis is still unclear. The aim of the present study was to investigate the effects of IL-33 on the procoagulant properties of human monocytes and monocyte-derived MVs. IL-33 induced a time- and concentration-dependent increase of monocyte TF mRNA and protein levels via binding to the ST2-receptor and activation of the NFκB-pathway. The IL-33 treated monocytes also released CD14+TF+ MVs and IL-33 was found to increase the TF activity of both the isolated monocytes and monocyte-derived MVs. The monocytes were classified into subsets according to their CD14 and CD16 expression. Intermediate monocytes (IM) showed the highest ST2 receptor expression, followed by non-classical monocytes (NCM), and classical monocytes (CM). IL-33 induced a significant increase of TF only in the IM (p<0.01), with a tendency in NCM (p=0.06), but no increase was observed in CM. Finally, plasma levels of IL–33 were positively correlated with CD14+TF+ MVs in patients undergoing carotid endarterectomy (r=0.480; p=0.032; n=20). We hereby provide novel evidence that the proinflammatory cytokine IL-33 induces differential TF expression and activity in monocyte subsets, as well as the release of procoagulant MVs. In this manner, IL-33 may contribute to the formation of a prothrombotic state characteristic for cardiovascular disease.Supplementary Material to this article is available online at www.thrombosis-online.com.

Statins and Inflammation in Cardiovascular Disease

2018 ◽  
Vol 23 (46) ◽  
pp. 7027-7039 ◽  
Author(s):  
Georgia Vogiatzi ◽  
Evangelos Oikonomou ◽  
Gerasimos Siasos ◽  
Sotiris Tsalamandris ◽  
Alexandros Briasoulis ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Lipid Lowering ◽  
Hmg Coa Reductase ◽  
Ample Evidence ◽  
Reductase Inhibitors ◽  
Immune System Activation ◽  
Hmg Coa Reductase Inhibitors ◽  
Anti Inflammatory ◽  
Artery Disease ◽  
Coa Reductase

Background: Chronic inflammation and immune system activation underlie a variety of seemingly unrelated cardiac conditions including not only atherosclerosis and the subsequent coronary artery disease but also peripheral artery disease, hypertension with target organ damage and heart failure. The beneficial effects of HMG-CoA reductase inhibitors or statins are mainly attributed to their ability to inhibit hepatic cholesterol biosynthesis. Beyond their lipid lowering activity, ample evidence exists in support of their potent anti-inflammatory properties which initiate from the inhibition of GTPase isoprenylation, activating a cataract of secondary pathways and extend to the inhibition and blocking of immune cell activation and interaction. </P><P> Objective: To summarize the anti-inflammatory mechanisms of statins in clinical and experimental settings in cardiovascular disease. </P><P> Methods: A systematic search of PubMed and the Cochrane Database was conducted in order to identify the majority of trials, studies, current guidelines and novel articles related to the subject. </P><P> Results: In vitro, statins have immuno-modulatory and anti-inflammatory effects, and they can exert antiatherosclerotic effects independently of their hypolipidemic actions. In addition, positive results have emerged from mechanistic and experimental studies on the active role of HMG-CoA reductase inhibitors in HF. By extrapolating those data in clinical setting, we further understand how HMG-CoA reductase inhibitors can beneficially affect not only systolic but also diastolic HF. </P><P> Conclusion: In this review article, we present the basic pathophysiologic data supporting the anti-inflammatory actions of statins in clinical and experimental settings and we link these mechanisms with confirmatory clinical data on the potent non lipid lowering effects of HMG-CoA reductase inhibitors.

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