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Acute Coronary Syndromes (ACS) are a group of disorders caused by the significant reduction of circulation in coronary arteries. The most common reason of the dysfunction is a blood clot formed in place of plaque rupture. The role of scavenger receptors in development and progression of atherosclerosis has been confirmed in many animal experiments,...
Similar publications
Background: Acute coronary syndrome is one of the leading causes of morbidity and mortality worldwide. Intracoronary thrombosis caused by atherosclerotic unstable plaque rupture or erosion is considered as main pathological basis. There have no identified biomarkers about diagnosis of unstable angina and prognosis of acute myocardial infarction.
Me...
Citations
... 53 In patients with ACS, CD36 receptor expression on circulating monocytes may be strongly associated with the late stage of atherosclerosis, because the onset of acute symptoms is characterized by increased monocyte and macrophage activity, as well as a very high level of inflammation in the body. 51 In addition, a positive correlation between CD36 expression in the aorta and CD36 expression on peripheral blood mononuclear cells has also been described. 54 The results should be interpreted with considerations since patients were under treatment. ...
Background
Atherosclerosis plays an important role in the pathophysiology of acute coronary syndrome (ACS). CD36 is a scavenger receptor involved in lipid metabolism. Some single‐nucleotide variants in the non‐coding region could indirectly alter the expression and the function of the protein.
Objective
The aim of this study was to investigate the gene and protein expression associated with CD36 variants (rs1194182;C > G; rs1049654;C > A, rs1334512;G > T, and rs3211892;G > A) in ACS patients from the western Mexican population.
Methods
We recruited 310 ACS patients and 308 subjects in the control group (CG). Genotyping was determined by TaqMan SNP genotyping assays. CD36 expression at the mRNA level was quantified by TaqMan gene expression assays. Soluble CD36 (sCD36) was measured by enzyme‐linked immunosorbent assay.
Results
We show that rs1194182G > C variant provides a protective effect with a 1.7‐fold lower susceptibility to develop ACS (p = 0.03); however, this association was masked by diabetes and dyslipidemia. We observed a higher sCD36 concentration in patient with ST‐segment elevation myocardial infarction (STEMI) compared with patients with unstable angina (UA) (p = 0.038). Likewise, in diabetic patients versus non‐diabetic (p < 0.001). We observed in patients an increase in CD36 mRNA expression (1.91 times higher) than in the CG (p = 0.02).
Conclusion
The rs1194182 seems to be associated with diabetes in a risky manner, in ACS patients and protective for dyslipidemia in both groups. The concentration of sCD36 seems to be associated with the clinical spectrum of the ACS patients and the presence of diabetes, since patients with STEMI present significantly elevated level compared with UA.
... Though MSR1 was considered a receptor specific to macrophages in their first descriptions [2][3][4], more recent publications have described its presence in other types of cells (especially tissue cells) such as vascular smooth muscle cells, endothelial cells, human lung epithelial cells, microglia, astrocytes, and murine embryonic fibroblasts. Few studies using peripheral blood mononuclear cell (PBMC) samples have reported the MSR1 gene [5,6] or protein [7,8] expression. MSR1 is implicated in many physiological and pathological processes associated with macrophages, including atherosclerosis and other diseases of the heart, endotoxemia, sepsis, viral infections, host defenses, Alzheimer's disease, lung injury, and bone metabolism [9]. ...
... Few published studies have analyzed the expression of MSR1 on the surface of PBMCs, and those that have evidenced expression have done so in subsets of monocytes in diseases such as acute coronary syndromes [6] and in systemic sclerosis [7]. Moreover, a novel subpopulation of PBMCs was found that expresses MSR1 and markers of fibrocytes and M2 macrophages, which seem to be the origin of dermal fibrosis-creating scars in patients presenting severe burns [8]. ...
Background:
Macrophage scavenger receptor 1 (MSR1) has mostly been described in macrophages, but we previously found a significant gene expression increase in peripheral blood mononuclear cells (PBMCs) of asthmatic patients.
Objective:
To confirm those results and to define its cellular origin in PBMCs.
Methods:
Four groups of subjects were studied: healthy controls (C), nonallergic asthmatic (NA), allergic asthmatic (AA), and chronic obstructive pulmonary disease (COPD) patients. RNA was extracted from PBMCs. MSR1 gene expression was analyzed by RT-qPCR. The presence of MSR1 on the cellular surface of PBMC cellular subtypes was analyzed by confocal microscopy and flow cytometry.
Results:
MSR1 gene expression was significantly increased in the three clinical conditions compared to the healthy control group, with substantial variations according to disease type and severity. MSR1 expression on T cells (CD4+ and CD8+), B cells, and monocytes was confirmed by confocal microscopy and flow cytometry. In all clinical groups, the four immune cell subtypes studied expressed MSR1, with a greater expression on B lymphocytes and monocytes, exhibiting differences according to disease and severity.
Conclusions:
This is the first description of MSR1's presence on lymphocytes' surfaces and reinforces the potential role of MSR1 as a player in asthma and COPD.
... 6 Notably, we found higher CD36 transcript levels in circulating mononuclear cells from patients with severe CAD who had experienced recent MI (typically at least seven days earlier) compared to patients with no CAD, consistent with the previous research. 39 The upregulation of EEF2K mRNA expression in this cohort suggests that eEF2K may be involved in the process of plaque destabilization, although another explanation could be that both EEF2K and CD36 are upregulated in mononuclear cells as an acute phase reaction to MI. This requires further evaluation particularly with a view to clinical translation. ...
Eukaryotic elongation factor 2 kinase (eEF2K) is an atypical protein kinase that controls protein synthesis in cells under stress. Although well studied in cancer, less is known about its roles in chronic inflammatory diseases. Here, we examined its regulation of macrophage cholesterol handling in the context of atherosclerosis. eEF2K mRNA expression and protein activity were upregulated in murine bone marrow‐derived macrophages (BMDMs) exposed to oxidized low‐density lipoprotein cholesterol (oxLDL). When incubated with oxLDL, BMDMs from eEF2K knockout (Eef2k−/−) mice formed fewer Oil Red O⁺ foam cells than Eef2k+/+ BMDMs (12.5% ± 2.3% vs. 32.3% ± 2.0%, p < .01). Treatment with a selective eEF2K inhibitor, JAN‐384, also decreased foam cell formation for C57BL/6J BMDMs and human monocyte‐derived macrophages. Disabling eEF2K selectively decreased protein expression of the CD36 cholesterol uptake receptor, mediated by a reduction in the proportion of translationally active Cd36 mRNA. Eef2k−/− mice bred onto the Ldlr−/− background developed aortic sinus atherosclerotic plaques that were 30% smaller than Eef2k+/+‐Ldlr−/− mice after 16 weeks of high cholesterol diet (p < .05). Although accompanied by a reduction in plaque CD36⁺ staining (p < .05) and lower CD36 expression in circulating monocytes (p < .01), this was not associated with reduced lipid content in plaques as measured by oil red O staining. Finally, EEF2K and CD36 mRNA levels were higher in blood mononuclear cells from patients with coronary artery disease and recent myocardial infarction compared to healthy controls without coronary artery disease. These results reveal a new role for eEF2K in translationally regulating CD36 expression and foam cell formation in macrophages. Further studies are required to explore therapeutic targeting of eEF2K in atherosclerosis.
... Результаты клинических исследований, в которых изучались особенности экспрессии CD36 на циркулирующих моноцитах у пациентов с атеросклерозом неоднородны и противоречивы. В целом ряде работ было продемонстрировано увеличение экспрессии CD36 на циркулирующих моноцитах у пациентов с атеросклеротическими ССЗ [2,6]. В других исследованиях, включавших пациентов с бессимптомным атеросклерозом, напротив, было установлено снижение экспрессии CD36 на моноцитах в сравнении с группами контроля [3,8]. ...
It is known that chronic activation of innate immunity and persistent low-intensity inflammation play a crucial role in the initiation and progression of atherosclerosis. It was found that atherogenic lipoproteins can act as inducers of the inflammatory response through ligand-receptor interaction with pattern-recognizing receptors of immunocompetent cells, such as CD36 (SR-B2) and Toll-like receptors. It is suggested that expression of CD36 on circulating monocytes may represent the burden of systemic atherosclerosis and, therefore, act as its diagnostic marker. The aim of the present study was to assess the intensity of CD36 expression on circulating monocytes of different subpopulations in patients without established cardiovascular disease (CVD) depending on the extent of subclinical atherosclerosis of peripheral arteries. One hundred patients without established atherosclerotic CVD, 49 (49.0%) men and 51 (51.0%) women, were included in the study. Monoclonal antibody conjugates were used to phenotype monocyte subpopulations. The expression of CD36 on CD14++CD16- monocytes (classical monocytes), CD14+CD16+ monocytes (intermediate monocytes), CD14+CD16++ monocytes (non-classical monocytes) was determined by the average fluorescence intensity. There was a statistically significant decrease in CD36 expression intensity on classical and non-classical monocytes with increasing number of vascular basins affected by atherosclerosis. A statistically significant decrease in CD36 expression intensity on classical and non-classical monocytes was found in the patients with two vascular beds lesions in comparison with patients with a single vascular bed lesion upon pairwise comparisons.
... Так, у больных сахарным диабетом 2 типа и ИБС отмечалось увеличение экспрессии CD36 на циркулирующих моноцитах, что прямо коррелировало с уровнем гликированного гемоглобина и ХС ЛПНП [12]. В ряде исследований также установлено повышение интенсивности экспрессии CD36 на моноцитах лиц с острыми кардиоваскулярными событиями [8,13]. У пациентов без сахарного диабета и установленных атеросклеротических ССЗ, напротив, продемонстрировано снижение выраженности экспрессии CD36 на циркулирующих моноцитах, связанное с субклиническим атеросклерозом или факторами риска ССЗ. ...
... MFAP4 [88], ALOX15 [89], COL1A1 [90], APOA1 [91], PDE5A [92], CX3CR1 [93], THY1 [94], GREM1 [95], FMOD (fibromodulin) [96], NPPA (natriuretic peptide A) [97], LTBP2 [98], LUM (lumican) [99], IL34 [100], NRG1 [101], CXCL14 [102], CXCL10 [103], ACE (angiotensin I converting enzyme) [104], CFTR (ystic fibrosis transmembrane conductance regulator) [105], S100A8 [106], S100A9 [106], HP (haptoglobin) [107], AGTR1 [108], ATP2A2 [109], IL10 [110], EDN1 [111], TLR2 [112], MCEMP1 [113], TPO (thyroid peroxidase) [114], CD163 [115], IL18R1 [116], KCNA7 [117] and CALCRL (calcitonin receptor like receptor) [118] have an important role in HF. Li [129] showed that CCR7, FCN1, ESM1, F8 (coagulation factor VIII), C1QTNF1, ALOX5 and MSR1 were an important target gene for coronary artery disease. STAB2 have been suggested to be associated with venous thromboembolic disease [130]. ...
Introduction
Heart failure (HF) is a heterogeneous clinical syndrome and affects millions of people all over the world. HF occurs when the cardiac overload and injury, which is a worldwide complaint. The aim of this study was to screen and verify hub genes involved in developmental HF as well as to explore active drug molecules.
Methods
The expression profiling by high throughput sequencing of GSE141910 dataset was downloaded from the Gene Expression Omnibus (GEO) database, which contained 366 samples, including 200 heart failure samples and 166 non heart failure samples. The raw data was integrated to find differentially expressed genes (DEGs) and were further analyzed with bioinformatics analysis. Gene ontology (GO) and REACTOME enrichment analyses were performed via ToppGene; protein–protein interaction (PPI) networks of the DEGs was constructed based on data from the HiPPIE interactome database; modules analysis was performed; target gene—miRNA regulatory network and target gene—TF regulatory network were constructed and analyzed; hub genes were validated; molecular docking studies was performed.
Results
A total of 881 DEGs, including 442 up regulated genes and 439 down regulated genes were observed. Most of the DEGs were significantly enriched in biological adhesion, extracellular matrix, signaling receptor binding, secretion, intrinsic component of plasma membrane, signaling receptor activity, extracellular matrix organization and neutrophil degranulation. The top hub genes ESR1, PYHIN1, PPP2R2B, LCK, TP63, PCLAF, CFTR, TK1, ECT2 and FKBP5 were identified from the PPI network. Module analysis revealed that HF was associated with adaptive immune system and neutrophil degranulation. The target genes, miRNAs and TFs were identified from the target gene—miRNA regulatory network and target gene—TF regulatory network. Furthermore, receiver operating characteristic (ROC) curve analysis and RT-PCR analysis revealed that ESR1, PYHIN1, PPP2R2B, LCK, TP63, PCLAF, CFTR, TK1, ECT2 and FKBP5 might serve as prognostic, diagnostic biomarkers and therapeutic target for HF. The predicted targets of these active molecules were then confirmed.
Conclusion
The current investigation identified a series of key genes and pathways that might be involved in the progression of HF, providing a new understanding of the underlying molecular mechanisms of HF.
... At the cellular level, all three vegetal oils were taken up by macrophages and caused foam cell formation. This change in the expression pattern has been observed in peritoneal macrophages isolated from obese mice, and blood monocytes from patients suffering from severe atherosclerosis (38)(39)(40). In principle, one could even use intraperitoneal peanut oil injection as a fast model to obtain viable foam cells for in vitro experiments. ...
Oil is frequently used as a solvent to inject lipophilic substances into the peritoneum of laboratory animals. Although mineral oil causes chronic peritoneal inflammation, little is known whether other oils are better suited. We show that olive, peanut, corn, or mineral oil causes xanthogranulomatous inflammation with depletion of resident peritoneal macrophages. However, there were striking differences in the severity of the inflammatory response. Peanut and mineral oil caused severe chronic inflammation with persistent neutrophil and monocyte recruitment, expansion of the vasculature, and fibrosis. Corn and olive oil provoked no or only mild signs of chronic inflammation. Mechanistically, the vegetal oils were taken up by macrophages leading to foam cell formation and induction of cell death. Olive oil triggered caspase-3 cleavage and apoptosis, which facilitate the resolution of inflammation. Peanut oil and, to a lesser degree, corn oil, triggered caspase-1 activation and macrophage pyroptosis, which impair the resolution of inflammation. As such, intraperitoneal oil administration can interfere with the outcome of subsequent experiments. As a proof of principle, intraperitoneal peanut oil injection was compared with its oral delivery in a thioglycolate-induced peritonitis model. The chronic peritoneal inflammation due to peanut oil injection impeded the proper recruitment of macrophages and the resolution of inflammation in this peritonitis model. In summary, the data indicate that it is advisable to deliver lipophilic substances, like tamoxifen, by oral gavage instead of intraperitoneal injection.
Implications
This work contributes to the reproducibility of animal research by helping to understand some of the undesired effects observed in animal experiments.
... CD36 is involved in the onset and progression of atherosclerosis, ranging from endothelial dysfunction to thrombus formation. CD36 represents a promising therapeutic target for atherosclerosis statin-treated patients with acute coronary syndromes exhibited lower expression of CD36 [76]. Moreover, statin-treated subjects diminished the proportion of macrophage with low-CD36 in adipose tissue [77]. ...
Purpose of review:
Atherosclerosis is a chronic disease characterized by lipid retention and inflammation in the artery wall. The retention and oxidation of low-density lipoprotein (LDL) in sub-endothelial space play a critical role in atherosclerotic plaque formation and destabilization. Oxidized LDL (ox-LDL) and other modified LDL particles are avidly taken up by endothelial cells, smooth muscle cells, and macrophages mainly through several scavenger receptors, including CD36 which is a class B scavenger receptor and membrane glycoprotein.
Recent findings:
Animal studies performed on CD36-deficient mice suggest that deficiency of CD36 prevents the development of atherosclerosis, though with some debate. CD36 serves as a signaling hub protein at the crossroad of inflammation, lipid metabolism, and fatty acid metabolism. In addition, the level of soluble CD36 (unattached to cells) in the circulating blood was elevated in patients with atherosclerosis and other metabolic disorders. We performed a state-of-the-art review on the structure, ligands, functions, and regulation of CD36 in the context of atherosclerosis by focusing on the pathological role of CD36 in the dysfunction of endothelial cells, smooth muscle cells, monocytes/macrophages, and platelets. Finally, we highlight therapeutic possibilities to target CD36 expression/activity in atherosclerosis.
... The expression of CD36 is increased in macrophages, smooth muscle cells, and endothelial cells in atherosclerosis plaques [13]. However, previous studies of membrane CD36 in monocytes and macrophages require fresh blood samples for measurement [14][15][16][17], and thus were not well suited for large population-based epidemiological studies. To tackle this issue, Handberg et al. [18] developed an assay to analyze the stored plasma samples, and identified a circulating form of CD36 in human plasma. ...
Background and aims:
CD36 is a cholesterol receptor involved in the uptake of oxidized low-density lipoprotein cholesterol and development of atherosclerotic plaques. Cross-sectional studies have shown correlations between plasma CD36 and atherosclerosis but no prospective study has examined the association yet. We prospectively examined the association between plasma CD36 levels and risk of incident coronary heart disease (CHD) in a Danish population.
Methods:
Plasma CD36 levels were measured in a case-cohort study nested within the Danish population-based cohort, the Diet, Cancer and Health Study. A total of 1963 incident CHD events occurred between baseline (1993-1997) and 2008, and a sub-cohort of 1759 participants were randomly selected as reference. Cox proportional hazard regression models were used to compute the hazard ratio (HR) and corresponding 95% confidence interval (CI).
Results:
After adjusting for CHD risk factors, including history of hypercholesterolemia and diabetes, elevated plasma CD36 levels were not associated with higher CHD risk in the total population, and the HR comparing the highest versus lowest tertile of CD36 levels was 1.02 (95% CI: 0.84-1.23). High CD36 levels were only found to be associated with risk of CHD in combination with prevalent diabetes (HR = 2.83, 95% CI: 1.08-7.45) vs. the joint reference group of lowest CD36 tertile and no diabetes.
Conclusions:
Plasma CD36 levels were not predictive of CHD risk in the general population.
... Similarly, the scavenger receptor CD36 involved in oxLDL recognition and foam cell formation was more greatly expressed [35,36] in classical and intermediate monocytes from the UA group. These findings are in line with those of previous studies reporting the upregulation of CD36 expression in the monocytes of patients with ACS [37]. Moreover, it is reported that the activation of CD36 by oxLDL results in the inhibition of migration of monocytes and macrophages, thus representing a mechanism of cell retention in atherosclerotic plaques, allowing for disease progression . ...
Background and aims:
Macrophages derived from monocytes play an important role in atherosclerosis progression. Subpopulations of circulating classical, intermediate, and non-classical monocytes possess distinct functions and phenotypes, and participate in the pathogenesis of disease. The aim of this study was to compare the quantity and phenotypes of circulating monocyte subpopulations in patients with established atherosclerosis and healthy control individuals. Additionally, the study aimed to provide insight into the functional activity of monocytes against a heat shock protein (HSP60).
Methods:
Chemokine and pattern recognition receptors in monocyte subsets obtained from peripheral blood of acute and chronic coronary artery disease patients and controls were quantified by flow cytometry. Furthermore, monocytes from healthy controls were stimulated in vitro with HSP60, and the cytokines produced by them were evaluated by flow cytometry.
Results:
Eighteen controls (C), 34 individuals with risk factors for cardiovascular disease (RF), 32 patients with stable angina (SA), and 16 patients with unstable angina (UA) were enrolled in the study. The absolute count of intermediate monocytes was found to be increased in patients of the UA group; high frequencies of the chemokine receptors CCR2, CCR5, and CX3CR1 were also observed in this subpopulation. Moreover, the pattern recognition receptors TLR2 and TLR4 were more frequent in intermediate monocytes from the UA group. Furthermore, the intermediate monocytes from healthy individuals produced IL-12p70 after stimulation with HSP60.
Conclusions:
Our results show that intermediate monocytes of UA patients exhibited an enhanced expression of the receptors involved in the recognition of damage-associated molecular patterns (DAMPs) and enhancement of the migratory function. Hence, they might contribute to the propagation and progression of inflammation observed in atherosclerosis, especially in the acute setting.
