Human monocyte characteristics are altered in hypercholesterolaemia

doi:10.1016/0021-9150(91)90112-G

Atherosclerosis

Volume 90, Issues 2–3, October 1991, Pages 175-181

https://doi.org/10.1016/0021-9150(91)90112-G Get rights and content

Abstract

Peripheral blood monocytes are involved during atherogenesis in adhering to endothelium, migrating into the subendothelial space and taking-up lipoproteins to become macrophage/foam cells. We have assessed whether peripheral blood monocyte characteristics are altered in human hyperlipidaemia in age/sex/smoking status matched pairs of patients and controls. Monocytes from the hypercholesterolaemic patients, as opposed to the controls, were more sensitive to stimulation by the agonist, N-formylmethionyl-leucyl-phenylalanine, with respect to chemokinesis (stimulation index 1.48 ± 0.17 vs. 1.10 ± 0.14), chemotaxis (4.05 ± 0.55 vs. 2.72 ± 0.24) and adhesion to porcine aortic endothelial monolayers (1.26 ± 0.05 vs. 1.17 ± 0.06). The patients' monocyte total surface expression of the adhesion glycoprotein $CD11b CD18$ (37.5 ± 7.1 vs. 36.0 ± 7.1), but not $CD11c CD18$ (31.6 ± 7.2 vs. 31.4 ± 6.8), was increased; however, the monocytes in hyperlipidaemia were larger (9.15 ± 0.11 μm vs. 8.98 ± 0.11 μm) such that the surface density of $CD11b CD18$ was not altered (0.144 ± 0.029 vs. 0.142 ± 0.029). The data suggest that circulating monocytes are functionally different in hypercholesterolaemia. This may explain the increased involvement by monocytes in hypercholesterolaemia-related atherogenesis.

References (38)

M. Suzuki et al.
Accumulation of lipids in the leukocytes of rats fed atherogenic diets
J. Lipid Res.
(1964)
H. Saito et al.
Influence of cholesterol feeding on the production of eicosanoids, tissue plasminogen activator and superoxide anion (O₂⁻) by rabbit blood monocytes
Atherosclerosis
(1986)
H.P. Hartung et al.
Chemically modified low density lipoproteins as inducers of enzyme release from macrophages
FEBS Lett.
(1985)
P.M.W. Bath et al.
Monocyte-lymphocyte discrimination in a new microtitre-based adhesion assay
J. Immunol. Methods
(1989)
W. Falk et al.
A 48-well micro chemotaxis assembly for rapid and accurate measurement of leukocyte migration
J. Immunol. Methods
(1980)
P.M.W. Bath et al.
Endothelin and PDGF do not stimulate peripheral blood monocyte chemotaxis, adhesion to endothelium and superoxide production
Exp. Cell. Res.
(1990)
A.-M. Gladwin et al.
Mac-1 mediates human monocyte adherence to endothelium via a protein kinase C dependent mechanism
Biochim. Biophys. Acta
(1990)
M. Patarroyo et al.
Leukocyte adhesion to cells in immune and inflammatory responses
Lancet
(1989)
R. Ross
The pathogenesis of atherosclerosis — an update
N. Engl. J. Med.
(1986)
W.J.S. Still et al.
Electron microscope study of experimental atherosclerosis in the rat
Am. J. Pathol.
(1962)

R.G. Gerrity

The role of the monocyte in atherogenesis: I. Transition of blood-borne monocytes into foam cells in fatty lesions

Am. J. Pathol.

(1981)

D. Steinberg et al.

Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity

New Engl. J. Med.

(1989)

M.T. Quinn et al.

Endothelial cell-derived chemotactic activity for mouse peritoneal macrophages and the effects of modified forms of low density lipoprotein

J.A. Berliner et al.

Monocyte chemotactic factor produced by large vessel endothelial cells in vitro

Arteriosclerosis

(1986)

M. Suzuki et al.

Circulating lipophages, serum lipids, and atherosclerosis in rats

Arch. Pathol.

(1967)

R.G. Gerrity et al.

Dietary induced atherogenesis in swine

Am. J. Pathol.

(1979)

K.A. Rogers et al.

Dietary cholesterol-induced changes in macrophage characteristics. Relationship to atherosclerosis

Am. J. Pathol.

(1986)

J.L. Kelley et al.

Influence of hypercholesterolaemia and cholesterol accumulation on rabbit carrageenan granuloma macrophage activation

Am. J. Pathol.

(1988)

J.R. Diamond et al.

Altered functional characteristics of rat macrophages during nephrosis

(1989)

Cited by (37)

Increased monocyte to high-density lipoprotein cholesterol ratio is associated with TIMI risk score in patients with ST-segment elevation myocardial infarction
2018, Revista Portuguesa de Cardiologia
Citation Excerpt :
Various studies have shown the association of CAD and white blood cell counts. Bath et al.16 reported that monocytes from hypercholesterolemic patients, as opposed to controls, were more sensitive to stimulation by chemoattractant agents with respect to chemokinesis. This may explain the increased involvement of monocytes in hypercholesterolemia-related atherogenesis.
The monocyte to high-density lipoprotein cholesterol ratio (MHR) has recently been proposed as a new predictor and prognostic indicator in cardiovascular disease. The TIMI risk score predicts short-term mortality in ST-elevation myocardial infarction (STEMI) patients. However, there have been no studies regarding the association between MHR and TIMI score in patients with STEMI.
A total of 161 patients admitted to our hospital were prospectively enrolled between January 2014 and June 2016. Of these, 111 consecutive patients with a diagnosis of STEMI who underwent primary percutaneous coronary intervention (PCI) were selected as the STEMI group, and the remaining 50 patients, who had angiographically normal coronary arteries, were selected as the control group. The 111 STEMI patients were then divided into two subgroups based on TIMI scores.
MHR was significantly higher in the STEMI group than in the control group (1.71±0.47 vs. 2.21±0.98, p=0.001) and was significantly higher in the high TIMI score group than in the low TIMI score group (1.80±0.59 vs. 2.42±1.09, p=0.001). In multivariate logistic regression analysis, MHR was the only independent predictor of acute STEMI and high TIMI score. In correlation analysis, there was a significant positive correlation between MHR and TIMI score in STEMI patients (r=0.479, p<0.001). The cutoff value of MHR for high TIMI score in patients with STEMI was 2.409, with a sensitivity of 43.06% and a specificity of 87.18% (AUC 0.669; 95% CI 0.569-0.8769; p=0.003) on ROC curve analysis.
This study indicates that MHR is independently and significantly associated with TIMI score in patients with STEMI. MHR is a novel inflammation-based marker and may be an independent predictor of future cardiovascular events in patients with STEMI.
A relação entre a contagem de monócitos e o nível de lipoproteína de alta densidade do colesterol (MHR) foi recentemente apresentada como um novo preditor e indicador prognóstico de doenças cardiovasculares. O score de risco TIMI prediz em curto prazo a mortalidade em doentes com STEMI. Contudo, não há estudo disponível acerca da associação entre o MHR e o score TIMI em doentes com STEMI.
Foram recrutados 161 doentes prospetivamente entre janeiro de 2014 e junho de 2016. Dos 161 doentes, 111 foram admitidos consecutivamente no nosso hospital com o diagnóstico de STEMI e foram submetidos a PCI primária, foram designados como o grupo STEMI, os restantes 50 doentes fizeram angiografia com artérias coronárias normais e foram selecionados como grupo controle. Os 111 doentes com STEMI foram ainda divididos em dois subgrupos, de acordo com o score de risco TIMI.
O MHR foi significativamente mais alto no grupo STEMI quando comparado com o grupo controle (1,71±0,47 versus 2,21±0,98, p=0,001) e foi significativamente mais alto no subgrupo de alto risco TIMI, quando comparado com o subgrupo de baixo risco TIMI (1,80±0,59 versus 2,42±1,09, p=0,001). O modelo de regressão logística multivariável demonstrou que o MHR só foi preditor independente no grupo STEMI com score TIMI de alto risco. Na análise de correlação, houve uma correlação positiva significativa entre o MHR e o score TIMI em doentes com STEMI (r=0,479, p<0,001). O valor de cut-off do MHR para o score TIMI alto em doentes STEMI foi 2,409 com uma sensibilidade de 43,06% e uma especificidade de 87,18% (AUC, 0,669; 95% com um intervalo de confiança de [CI], 0,569-0,8769; p=0,003) na análise de curva de ROC.
Este estudo indicou que o MHR está independente e significativamente associado ao score TIMI em doentes com STEMI. O MHR é um novo marcador de base inflamatória e pode ser um preditor independente de eventos cardiovasculares futuros em doentes com STEMI.
Monocytes as a diagnostic marker of cardiovascular diseases
2012, Immunobiology
Citation Excerpt :
In 1991 Bath et al. have examined migratory properties of monocytes from healthy individuals and patients with hypercholisterolaemia. It was found that monocytes from patients migrate much better than the monocytes from healthy individuals (Bath et al. 1991). Further studies of macrophage migration capabilities are largely related to anti-atherosclerothic therapies that influence the migratory properties of monocytes.
Inflammation is an important pathogenic factor of cardiovascular diseases. Inflammatory processes induce the organism systemic changes that are sensed by the cells of innate immune system. These systemic changes include increased concentrations of soluble factors capable of activating monocytes in the blood circulation therefore monocytes represent highly attractive cell population for diagnostic use. To date various parameters of circulating monocytes were associated with cardiovascular diseases. These comprise monocyte count, increased adhesive properties, alteration of lipid metabolism, phagocytosis and endocytosis of LDL. Search for markers, better suitable for clinical use led to identification of monocyte population heterogeneity. One of the best studied markers for identification of monocyte subpopulation is CD16. Although there is no consensus regarding the origin and composition of various monocyte subpopulations, association of increased size of CD16+ monocyte population with atherosclerosis is well established. Further surface markers of monocytes found to be associated with cardiovascular diseases are CD18, CD11b, CXCR1, CD36 and STAB1. Functional studies performed on primary human monocytes support the importance of these molecules for the pathogenesis of cardiovascular diseases. Continuous research on monocyte biology leads to identification of perspective markers that show significant potential of clinical use. These include analysis of monocyte response to a challenge and level of mitochondrial DNA heteroplasmy. Further research involving genomic, proteomic and cell biology techniques supplemented with systems biology approaches for data analysis and computer simulations are required for defining molecular and functional parameters of monocytes to be used as a diagnostic tool or therapeutic target.
Mononuclear cell adhesion to collagen ex vivo is related to pulse pressure in elderly subjects
2000, Atherosclerosis
Mononuclear cells and platelets are intimately involved in the pathogenesis and complications of cardiovascular disease. Platelet activation has been reported in hypertension, though the activation-state of monocytes has received less attention. In this study the adhesiveness of monocytes and platelets was assessed and any relationship between the adhesive properties of these cellular elements and plasma levels of soluble adhesion molecules and blood pressure parameters determined. Fifty six elderly volunteers, of whom 32 were classified hypertensive (daytime SBP≥135 mmHg), underwent 24 h blood pressure monitoring, assessment of monocyte and platelet adhesion and measurement of the plasma soluble adhesion molecules ICAM-1, L-selectin, E-selectin and vWF. In the elderly hypertensive subjects, monocyte adhesion to collagen coated (P<0.05) and tissue culture plastic microwells (P<0.05) was significantly elevated and circulating levels of soluble ICAM-1 (P<0.01) and soluble E-selectin (P<0.05) were significantly raised compared to their normotensive counterparts. A significant correlation was found to exist between monocyte adhesion to collagen and daytime pulse pressure (r=0.39, P<0.01) and also between plasma levels of soluble E-selectin and clinic DBP (r=0.40, P<0.001). The increased monocyte adhesion witnessed in hypertensive subjects and with increasing pulse pressure may contribute to the increased risk of cardiovascular disease in hypertension. Whether this increased adhesiveness is a property of the monocytes, or reflects endothelial cell activation, remains to be determined.
The influence of treatment of hypercholesterolemic patients with simvastatin on plasma chemotactic activity and adherence of neutrophils
2000, International Journal of Cardiology
Background: there is some evidence to indicate that statins may affect the function of immune and inflammatory cells. This study investigates the influence of short term treatment with simvastatin on plasma chemotactic activity and adherence of polymorphonuclear neutrophils in hypercholesterolemic patients. Methods and results: 20 hypercholesterolemic patients (250–400 mg/dl) were given simvastatin (20 mg daily for 12 weeks). Peripheral blood samples were taken before and after 4 and 12 weeks of the therapy. The percentage of neutrophils adhering to plastic surface coated with albumin was significantly higher when cells were incubated with plasma obtained after 12 weeks of treatment with simvastatin in comparison with plasma collected before the therapy (unstimulated neutrophils: 5.945±0.475% vs. 8.155±0.96%, P=0.0477, stimulated neutrophils: 39.09±4.540% vs. 29.18±3.702%, P=0.032). There was a significant negative correlation between adherence of stimulated neutrophils and total cholesterol levels ((r)=−0.2796, 95% CI −0.4999 to −0.02526, r²=0.07817, P=0.032). Migration of neutrophils towards plasma obtained after 12 weeks of treatment with simvastatin was significantly higher than towards plasma collected before the therapy (7.038±1.127 vs. 4.505±0 618 P=0.0475). Conclusion: treatment of hypercholesterolemic patients with simvastatin increases the chemotactic activity of plasma and augments the adherence of human neutrophils.
Monocyte tissue factor response is decreased in patients with hyperlipidemia
1999, Thrombosis Research
Monocytes are potent regulators of blood coagulation through the expression of tissue factor (TF) on stimulation and of tissue factor pathway inhibitor (TFPI), a selective inhibitor of TF pathway. As hyperlipidemia can modify some monocyte functions, we compared the TF and TFPI expression by circulating monocytes and the plasma TFPI levels between 65 healthy normolipemic controls and 38 nontreated hyperlipemic patients. TF and TFPI relationships with plasma lipoproteins are also examined. TF and TFPI expression were evaluated in peripheral mononuclear cells after isolation from blood by density gradient centrifugation and after short culture with or without lipopolysaccharide (LPS). TF and TFPI activity and antigen were measured in mononuclear cell lysates using amidolytic assay and enzyme-linked immunosorbent assay, respectively. TFPI activity and antigen were measured in plasma using the same methods. Plasma factor VII (FVII) activity and antigen were also determined. LPS-stimulated monocyte TF activity and antigen were lower in hyperlipidemic patients than in controls (0.0001<p<0.03). This decrease of monocyte TF expression in hyperlipidemic patients was not related to an increase of monocyte TFPI. Monocyte TF activity was negatively correlated to atherogenic fractions and positively correlated to protective fractions, specially after ex vivo LPS stimulation. Increased TFPI and FVII plasma levels were found in hyperlipidemic patients compared to controls. These results indicate an impairment of TF production by circulating monocytes from hyperlipidemic subjects, which is linked to the increase of atherogenic lipoprotein fractions. Further studies are required to elucidate the mechanism of this inhibition.
High-density lipoprotein: Multipotent effects on cells of the vasculature
1999, International Review of Cytology
The epidemiological evidence showing a strong inverse correlation between the level of plasma high-density lipoprotein (HDL) and the incidence of heart disease suggests that HDL has a protective effect against cardiovascular disease. The mechanism of this protective effect has been the raison d'etre for much research. The ability of HDL to mediate cholesterol efflux from peripheral tissues has been used to explain the cardioprotective effect of HDL. However, there is little direct evidence to suggest that in subjects with low plasma levels of HDL the rate of cholesterol efflux from peripheral tissues is significantly reduced. This observation suggested that HDL may be mediating its protective effect through other mechanisms. This review provides an account of the burgeoning evidence that HDL has many effects on cellular processes, in addition to the effects on cholesterol efflux, and will illustrate the multipotency of this lipoprotein.

View all citing articles on Scopus

View full text

Research articleHuman monocyte characteristics are altered in hypercholesterolaemia

Abstract

J. Lipid Res.

Atherosclerosis

FEBS Lett.

J. Immunol. Methods

J. Immunol. Methods

Exp. Cell. Res.

Biochim. Biophys. Acta

Lancet

The pathogenesis of atherosclerosis — an update

N. Engl. J. Med.

Electron microscope study of experimental atherosclerosis in the rat

Am. J. Pathol.

The role of the monocyte in atherogenesis: I. Transition of blood-borne monocytes into foam cells in fatty lesions

Am. J. Pathol.

Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity

New Engl. J. Med.

Endothelial cell-derived chemotactic activity for mouse peritoneal macrophages and the effects of modified forms of low density lipoprotein

Monocyte chemotactic factor produced by large vessel endothelial cells in vitro

Arteriosclerosis

Circulating lipophages, serum lipids, and atherosclerosis in rats

Arch. Pathol.

Dietary induced atherogenesis in swine

Am. J. Pathol.

Dietary cholesterol-induced changes in macrophage characteristics. Relationship to atherosclerosis

Am. J. Pathol.

Influence of hypercholesterolaemia and cholesterol accumulation on rabbit carrageenan granuloma macrophage activation

Am. J. Pathol.

Altered functional characteristics of rat macrophages during nephrosis

Research article
Human monocyte characteristics are altered in hypercholesterolaemia