scholarly journals Macrophage uptake of low-density lipoprotein bound to aggregated C-reactive protein: possible mechanism of foam-cell formation in atherosclerotic lesions

2002 ◽  
Vol 366 (1) ◽  
pp. 195-201 ◽  
Author(s):  
Tao FU ◽  
Jayme BORENSZTAJN

Foam cells found in atherosclerotic lesions are believed to derive from macrophages that take up aggregated low-density lipoprotein (LDL) particles bound to the extracellular matrix of arterial walls. C-reactive protein (CRP) is an acute-phase protein found in atherosclerotic lesions, which when immobilized on a solid phase, can bind and cluster LDL particles in a calcium-dependent manner. In the present study, we examined whether CRP-bound aggregated LDL could be taken up by macrophages in culture. CRP molecules were aggregated in the presence of calcium and immobilized on the surface of polystyrene microtitre wells. Human LDL added to the wells bound to and aggregated on the immobilized CRP, also in a calcium-dependent manner. On incubation with macrophages, the immobilized CRP-bound LDL aggregates were readily taken up by the cells, as demonstrated by immunofluorescence microscopy, by the cellular accumulation of cholesterol and by the overexpression of adipophilin. Immunofluorescence microscopy and flow-cytometry analysis established that the uptake of the LDL—CRP complex was not mediated by the CRP receptor CD32. These observations with immobilized CRP and LDL, approximating the conditions that exist in the extracellular matrix of the arterial wall, thus suggest that CRP may contribute to the formation of foam cells in atherosclerotic lesions by causing the aggregation of LDL molecules that are then taken up by macrophages through a CD32-independent pathway.

1982 ◽  
Vol 156 (1) ◽  
pp. 230-242 ◽  
Author(s):  
F C de Beer ◽  
A K Soutar ◽  
M L Baltz ◽  
I M Trayner ◽  
A Feinstein ◽  
...  

C-reactive protein (CRP), the classical acute-phase protein, can bind phospholipids by virtue of its specific, calcium-dependent reactivity with phosphorylcholine residues. However, analysis of acute-phase serum by gel filtration and by density gradient ultracentrifugation showed that the CRP was in a free, uncomplexed form, despite the coexistent presence of the various classes of serum lipoproteins, all of which contain phospholipids. In contrast, when isolated CRP was aggregated by immobilization at a sufficient density on a solid phase and then exposed to normal human serum, it selectively bound low density lipoprotein (LDL) and traces of very low density lipoprotein. The reaction was calcium dependent and reversible by free phosphorylcholine but not by heparin. LDL isolated from normal plasma was also bound by aggregated CRP. CRP reacts in vitro with a wide variety of different ligands both of extrinsic and of autogenous origin, e.g., microbial products and damaged cell membranes, respectively. If CRP aggregated in vivo by complexing with these ligands than acquires the capacity to selectively bind LDL, the phenomenon may have significant implications for the function of CRP and for the metabolism, clearance, and deposition of LDL.


2000 ◽  
Vol 151 (1) ◽  
pp. 88
Author(s):  
S. Taskinen ◽  
P.T. Kovanen ◽  
H. Jarva ◽  
S. Meri ◽  
M.O. Pentikäinen

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bushra Yusuf ◽  
Ilya Mukovozov ◽  
Sajedabanu Patel ◽  
Yi-Wei Huang ◽  
Guang Ying Liu ◽  
...  

AbstractAtherosclerosis is characterized by retention of modified lipoproteins, especially oxidized low density lipoprotein (oxLDL) within the sub-endothelial space of affected blood vessels. Recruited monocyte-derived and tissue-resident macrophages subsequently ingest oxLDL by binding and internalizing oxLDL via scavenger receptors, particularly CD36. The secreted neurorepellent, Slit2, acting through its transmembrane receptor, Roundabout-1 (Robo-1), was previously shown to inhibit recruitment of monocytes into nascent atherosclerotic lesions. The effects of Slit2 on oxLDL uptake by macrophages have not been explored. We report here that Slit2 inhibits uptake of oxLDL by human and murine macrophages, and the resulting formation of foam cells, in a Rac1-dependent and CD36-dependent manner. Exposure of macrophages to Slit2 prevented binding of oxLDL to the surface of cells. Using super-resolution microscopy, we observed that exposure of macrophages to Slit2 induced profound cytoskeletal remodeling with formation of a thick ring of cortical actin within which clusters of CD36 could not aggregate, thereby attenuating binding of oxLDL to the surface of cells. By inhibiting recruitment of monocytes into early atherosclerotic lesions, and the subsequent binding and internalization of oxLDL by macrophages, Slit2 could represent a potent new tool to combat individual steps that collectively result in progression of atherosclerosis.


2008 ◽  
Vol 394 (1-2) ◽  
pp. 94-98 ◽  
Author(s):  
Sanjay K. Singh ◽  
Madathilparambil V. Suresh ◽  
Deborah C. Prayther ◽  
Jonathan P. Moorman ◽  
Antonio E. Rusiñol ◽  
...  

2005 ◽  
Vol 62 (11) ◽  
pp. 811-819
Author(s):  
Aleksandra Jovelic ◽  
Goran Radjen ◽  
Stojan Jovelic ◽  
Marica Markovic

Background/Aim. C-reactive protein is an independent predictor of the risk of cardiovascular events and diabetes mellitus in apparently healthy men. The relationship between C-reactive protein and the features of metabolic syndrome has not been fully elucidated. To assess the cross-sectional relationship between C-reactive protein and the features of metabolic syndrome in healthy people. Methods. We studied 161 military pilots (agee, 40?6 years) free of cardiovascular disease, diabetes mellitus and active inflammation on their regular annual medical control. Age, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglycerides, fasting glucose, glycosylated hemoglobin, blood pressure, smoking habit, waist circumference and body mass index were evaluated. Plasma C-reactive protein was measured by the immunonephelometry (Dade Behring) method. Metabolic syndrome was defined according to the National Cholesterol Education Program Expert Panel. Results. The mean C-reactive protein concentrations in the subjects grouped according to the presence of 0, 1, 2 and 3 or more features of the metabolic syndrome were 1.11, 1.89, 1.72 and 2.22 mg/L, respectively (p = 0.023) with a statistically, significant difference between those with 3, and without metabolic syndrome (p = 0.01). In the simple regression analyses C-reactive protein did not correlate with the total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, body mass index and blood pressure (p > 0.05). In the multiple regression analysis, waist circumference (? = 0.411, p = 0.000), triglycerides to high density lipoprotein cholesterol ratio (? = 0.774, p = 0.000), smoking habit (? = 0.236, p = 0.003) and triglycerides (? = 0.471, p = 0.027) were independent predictors of C-reactive protein. Conclusions. Our results suggested a cross-sectional independent correlation between the examined cardiovascular risk factors as the predominant features of metabolic syndrome and C-reactive protein in the group of apparently healthy subjects. The lack of correlation of C-reactive protein with the total cholesterol and low density lipoprotein cholesterol in our study may suggest their different role in the process of atherosclerosis and the possibility to determine C-reactive protein in order to identify high-risk subjects not identified with cholesterol screening.


2020 ◽  
Vol 5 (3) ◽  
pp. 676
Author(s):  
Rama Dhanivita Djamin

<p><em>Obesitas terjadi karena akumulasi lemak berlebih di dalam tubuh. Akumulasi lemak menimbulkan low grade inflammation pada jaringan adiposa, menyebabkan peningkatan sitokin inflamasi seperti tumor necrosis factor-alpha, interleukin-1 beta, dan interleukin-6 (IL-6). Peningkatan sekresi IL-6 merangsang hepar meningkatkan produksi protein fase akut. High sensitivity C-reactive protein (hs-CRP) sebagai penanda inflamasi merupakan protein fase akut. Low density lipoprotein (LDL-kolesterol) adalah lipoprotein yang paling banyak mengandung kolesterol. Peningkatan kadar hs-CRP dan kadar LDL-kolesterol pada obesitas diidentifikasi sebagai faktor risiko aterosklerosis. Penelitian ini bertujuan menganalisis hubungan hs-CRP dengan LDL-kolesterol pada penyandang obes, merupakan penelitian analitik rancangan potong lintang dilakukan  September 2018 sampai Agustus 2019. Kadar hs-CRP diperiksa dengan metode enzyme linked immunoassay (ELISA), sedangkan kadar LDL-kolesterol dengan metode kalkulasi (rumus Friedewald). Uji korelasi Spearman digunakan untuk menganalisi data, jika didapatkan nilai p&lt;0,05 korelasi dinyatakan bermakna. Subjek penelitian berjumlah 26 penyandang obes terdiri dari 6 laki-laki (23,1%) dan 20 perempuan (76,9%). Rerata umur subjek penelitian adalah 36,46(7,68) tahun. Rerata kadar hs-CRP dan kadar LDL-kolesterol adalah 5,08(1,28) mg/L dan  154,69(45,8) mg/dL. Analisis korelasi menunjukkan korelasi positif lemah dan tidak bermakna secara statistik antara kadar hs-CRP dengan kadar LDL-kolesterol (r= 0,333, p=0,096). Simpulan: Terdapat korelasi positif lemah antara kadar hs-CRP dengan kadar LDL-kolesterol pada penyandang obes.</em></p><p><strong><em>Kata kunci</em></strong><em>: </em><em>Obesitas, High Sensitivity C-Reactive, Low Density Lipoprotein</em><em></em></p>


2020 ◽  
Vol 73 (3) ◽  
pp. 569-573 ◽  
Author(s):  
Yevheniia H. Zaremba ◽  
Olha V. Smaliukh ◽  
Olena V. Zaremba-Fedchyshyn ◽  
Olha V. Zaremba ◽  
Andriy S. Kost ◽  
...  

The aim: Research of blood lipid spectrum, level of anti-inflammatory cytokines and C-reactive protein of coronary heart disease patients. Materials and methods: There was examined 61 patients with unstable angina, who had been on hospital care in the cardiology department of the Lviv National Emergency Hospital. Their average age was 68.3 ± 1.9 years. The control group included 20 generally healthy persons. There was estimated blood lipid spectrum, C-reactive protein, fibrinogen and proinflammatory cytokine of patients. Results: There was determined considerable increase total cholesterol, low density lipoprotein cholesterol, very low density lipoprotein cholesterol, triglycerides and coefficient of atherogenicity. High level of C-reactive protein and pro-inflammatory cytokines were detected in patients with unstable angina. Conclusions: In patients with unstable angina was revealed a significant increase of proinflammatory cytokines levels in the blood serum: interleukin-1β, interleukin-6, interleukin-17, TNF-α and C-reactive protein, fibrinogen, which indicates activation of the inflammatory process. In patients with unstable angina was detected a significant disorder of blood lipid spectrum. For its correction should be recommended diet and hypolipidemic agents.


Sign in / Sign up

Export Citation Format

Share Document