INTRODUCTION: Endarterectomy specimens represent a unique opportunity to study atherosclerosis. This review aims to summarize the recent knowledge of atherogenesis from studies characterizing a cellular composition of carotid endarterectomy specimens. EVIDENCE ACQUISITION: A non-systematic literature review was carried out to summarize recent knowledge regarding ex vivo analysis of carotid artery plaque composition. Upon evaluation of their relevance, and elaborate forward and backward search, 95 articles were included in the review. EVIDENCE SYNTHESIS: Despite the significant advancement of in vivo imaging techniques, the stroke prediction based on carotid artery plaque morphology is not reliable. Besides analyses of plaque morphology, present studies focus on precise characterization of the different immune cell types and elucidation of their role in plaque development. Plaque content analyses revealed the presence of various immune cells in carotid artery plaques. Presence of different immune cells subpopulations can be connected to some undesirable changes in plaque stability. CONCLUSIONS: Since the destabilization of the atherosclerotic plaque is a multifactorial process, a combination of various methods should be used to characterize the unstable plaques more accurately. In this context, studies characterizing plaque content from a cellular point of view could elucidate some processes underlying the plaque progression. Together with morphological evaluation, these analyses could enable more precise assessment of plaque stability.
- MeSH
- aterosklerotický plát patologie MeSH
- ateroskleróza imunologie patologie chirurgie MeSH
- CD antigeny analýza MeSH
- imunohistochemie MeSH
- karotická endarterektomie MeSH
- lidé MeSH
- makrofágy imunologie MeSH
- průtoková cytometrie MeSH
- stenóza arteria carotis imunologie patologie chirurgie MeSH
- T-lymfocyty imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- CD antigeny MeSH
OBJECTIVE: Blood monocyte subsets are emerging as biomarkers of cardiovascular inflammation. However, our understanding of human monocyte heterogeneity and their immunophenotypic features under healthy and inflammatory conditions is still evolving. RATIONALE: In this study, we sought to investigate the immunophenome of circulating human monocyte subsets. METHODS: Multiplexed, high-throughput flow cytometry screening arrays and computational data analysis were used to analyze the expression and hierarchical relationships of 242 specific surface markers on circulating classical (CD14++CD16-), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++) monocytes in healthy adults. RESULTS: Using generalized linear models and hierarchical cluster analysis, we selected and clustered epitopes that most reliably differentiate between monocyte subsets. We validated existing transcriptional profiling data and revealed potential new surface markers that uniquely define the classical (e.g., BLTR1, CD35, CD38, CD49e, CD89, CD96), intermediate (e.g., CD39, CD275, CD305, CDw328), and nonclassical (e.g., CD29, CD132) subsets. In addition, our analysis revealed phenotypic cell clusters, identified by dendritic markers CMRF-44 and CMRF-56, independent of the traditional monocyte classification. CONCLUSION: These results reveal an advancement of the clinically applicable multiplexed screening arrays that may facilitate monocyte subset characterization and cytometry-based biomarker selection in various inflammatory disorders.
- MeSH
- ateroskleróza diagnóza imunologie MeSH
- biodiverzita MeSH
- biologické markery metabolismus MeSH
- fenotyp MeSH
- imunofenotypizace metody MeSH
- krevní oběh MeSH
- lidé MeSH
- lipopolysacharidové receptory metabolismus MeSH
- monocyty fyziologie MeSH
- průtoková cytometrie MeSH
- receptory IgG metabolismus MeSH
- rychlé screeningové testy MeSH
- separace buněk MeSH
- shluková analýza MeSH
- zánět diagnóza imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
- lipopolysacharidové receptory MeSH
- receptory IgG MeSH
Although current treatment of hypertension and hypercholesterolemia is most effective, cardiovascular mortality still remains at 50 % in industrialized countries. This could be explained by the rather high contribution of the inflammatory process to atherogenesis development. Use of high-sensitivity C-reactive protein (hsCRP) determination in several large epidemiological studies has made it possible to document increased risk of myocardial infarction in individuals with slightly increased hsCRP concentrations, which could thus serve as a discriminatory factor in cardiovascular disease risk assessment. However, the situation is not that simple since hsCRP concentrations correlate significantly with BMI, age and smoking as major cardiovascular risk factors. Increased proportion of pro-inflammatory macrophages in visceral adipose tissue has also been shown to rise with BMI, age (differently in men and women) and non-HDL-cholesterol levels. It has been suggested that the pro-inflammatory status induced by a higher proportion of pro-inflammatory macrophages in visceral adipose tissue acts synergistically in atherogenesis development. Key words: atherosclerosis - cardiovascular disease - inflammation.
- Klíčová slova
- atherosclerosis - cardiovascular disease - inflammation,
- MeSH
- ateroskleróza * imunologie patofyziologie MeSH
- biologické markery MeSH
- C-reaktivní protein MeSH
- kardiovaskulární nemoci * MeSH
- lidé MeSH
- mediátory zánětu MeSH
- rizikové faktory MeSH
- zánět * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
- C-reaktivní protein MeSH
- mediátory zánětu MeSH
Atherosclerosis and disease of graft implanted to bypass occluded coronary or peripheral arteries are similar processes. Patency of implanted grafts is of paramount importance in respect to long-term outcomes. Although few cell types participate in atherosclerotic plaque formation, macrophages play a crucial role. In this article we review the fate of monocytes that infiltrate vessel wall following endothelium damage, and then undergo transformation to macrophages (identified as CD68 positive cells) and eventually lead to severe stenosis of vessel. Opposing biological activity of two subpopulations of macrophages and their impact on plaque instability and its calcification is also presented. At the end of this paper, a possible clinical significance of pre-existing, CD68 positive cell infiltration of vessel wall, applied as aortocoronary grafts, is discussed.
- MeSH
- antigeny diferenciační myelomonocytární metabolismus MeSH
- ateroskleróza imunologie patologie MeSH
- CD antigeny metabolismus MeSH
- koronární bypass * škodlivé účinky MeSH
- lidé MeSH
- makrofágy imunologie metabolismus patologie MeSH
- rejekce štěpu imunologie patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- antigeny diferenciační myelomonocytární MeSH
- CD antigeny MeSH
- CD68 antigen, human MeSH Prohlížeč
Oxidation of atherogenic low-density lipoproteins (LDL) plays a key role in the pathogenesis of atherosclerosis. Oxidation stress and inflammation are closely interrelated and they can potentiate one another. In the subendothelial space of the arterial intima, monocytes/macrophages become activated and phagocyte oxidized LDL (oxLDL) via scavenger receptors. It has been demonstrated that oxLDL forms complex with plasma β2-glycoprotein I (β2GPI) and becomes autoantigenic triggering synthesis of specific antiphosholipid antibodies. It has been documented that oxLDL/β2GPI in immune complex with IgG autoantibody is internalized by macrophages through the Fcγ receptor. Increased levels of oxLDL/β2GPI were first observed in patients with systemic lupus erythematodes (SLE) and antiphospholipid syndrome (APS), further in individuals with coronary heart disease (CHD) and type 2 diabetes mellitus (DM2T). In a prospective study, initial plasma concentrations of oxLDL/β2GPI correlated with the number and severity of cardiovascular events in patients with chronic CHD over a 2-year period.Key words: atherosclerosis - β2-glycoprotein I - inflammation - oxidative stress - oxLDL.
- MeSH
- ateroskleróza krev imunologie MeSH
- autoimunitní nemoci imunologie MeSH
- beta-2-glykoprotein I krev MeSH
- koronární nemoc krev imunologie patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipoproteiny LDL krev MeSH
- prospektivní studie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- beta-2-glykoprotein I MeSH
- lipoproteiny LDL MeSH
- oxidized low density lipoprotein MeSH Prohlížeč
Atherosclerosis has been recognized as an inflammatory/autoimmune disease. The long-standing low-grade inflammation which fuels its development is primarily focused on the components of the vessel wall. Originally, inflammation in atherogenesis was supposed to be driven by the pro-inflammatory Th1 cellular and cytokine immune response. On the basis of accumulating evidence, this view has been re-evaluated to include the Th17/Th1 axis which is shared by most diseases of sterile inflammation. The anti-inflammatory Th2 cellular and cytokine immune response is initiated concomitantly with the former two, the latter dampening their harmful reactions which culminate in full-blown atherosclerosis. Interleukin-33, a novel member of the IL-1 cytokine superfamily, was suggested to take part in the anti-atherogenic response by mediating the Th1-to-Th2 switch of the immune reactions. However, IL-33 is a multifaceted mediator with both pro- and anti-inflammatory activities, also called a "dual factor" or a "Janus face" interleukin. IL-33 occurs both in an extracellular (cytokine-like) and in a nuclear-bound (transcription factor-like) form, each of them performing distinct activities of their own. This review article presents the latest data relevant to IL-33's role in atherosclerosis and cardiac diseases as perceived by a cardiologist and a cardiac surgeon.
- Klíčová slova
- IL-33, Th1, Th17, Th2, atherosclerosis, cytokine, inflammation, transcription factor,
- MeSH
- ateroskleróza imunologie patologie MeSH
- buňky Th17 imunologie patologie MeSH
- interleukin 33 imunologie MeSH
- lidé MeSH
- srdeční selhání imunologie patologie MeSH
- Th1 buňky imunologie patologie MeSH
- Th2 buňky imunologie patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- IL33 protein, human MeSH Prohlížeč
- interleukin 33 MeSH
High-energy intake which exceeds energy expenditure leads to the accumulation of triglycerides in adipose tissue, predominantly in large-size adipocytes. This metabolic shift, which drives the liver to produce atherogenic dyslipidemia, is well documented. In addition, an increasing amount of monocytes/macrophages, predominantly the proinflammatory M1-type, cumulates in ectopic adipose tissue. The mechanism of this process, the turnover of macrophages in adipose tissue and their direct atherogenic effects all remain to be analyzed.
- MeSH
- ateroskleróza imunologie metabolismus patologie MeSH
- energetický metabolismus fyziologie MeSH
- inzulinová rezistence fyziologie MeSH
- lidé MeSH
- makrofágy imunologie metabolismus patologie MeSH
- obezita imunologie metabolismus patologie MeSH
- tuková tkáň imunologie metabolismus patologie MeSH
- tukové buňky imunologie metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Atherosclerosis is a degenerative inflammatory disease of the vascular wall, which is characterized by the formation of atherosclerotic plaques that contain lipids, activated smooth muscle cells, immune cells, foam cells, a necrotic core and calcified sites. In atherosclerosis pathology, monocytes and macrophages play the most important role by accumulating redundant LDL particles in their oxidized form and producing proinflammatory cytokines. Atherosclerotic plaque macrophages reveal distinct phenotypes that are distinguished into M1 (pro-inflammatory) and M2 (anti-inflammatory) macrophages. Numerous environmental signals (cytokines, microbial cell molecules) that are received by macrophages drive their polarization, but it must be determined whether this classification reflects different macrophage subtypes or plasticity and phenotypic tissue changes, but the balance between subsets is crucial. M1 macrophages are dominant in symptomatic atherosclerotic plaques, while M2 macrophages are more frequent in asymptomatic plaques. Nevertheless, a positive correlation of both M1 and M2 macrophages with atherosclerotic lesion severity was also observed.
- MeSH
- ateroskleróza diagnóza imunologie MeSH
- cytokiny imunologie MeSH
- lidé MeSH
- makrofágy imunologie MeSH
- zánět diagnóza imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- cytokiny MeSH
Over the last two decades, the amount of evidence corroborating an association between dental plaque bacteria and coronary diseases that develop as a result of atherosclerosis has increased. These findings have brought a new aspect to the etiology of the disease. There are several mechanisms by which dental plaque bacteria may initiate or worsen atherosclerotic processes: activation of innate immunity, bacteremia related to dental treatment, and direct involvement of mediators activated by dental plaque and involvement of cytokines and heat shock proteins from dental plaque bacteria. There are common predisposing factors which influence both periodontitis and atherosclerosis. Both diseases can be initiated in early childhood, although the first symptoms may not appear until adulthood. The formation of lipid stripes has been reported in 10-year-old children and the increased prevalence of obesity in children and adolescents is a risk factor contributing to lipid stripes development. Endothelium damage caused by the formation of lipid stripes in early childhood may lead to bacteria penetrating into blood circulation after oral cavity procedures for children as well as for patients with aggressive and chronic periodontitis.
- MeSH
- ateroskleróza komplikace imunologie mikrobiologie patologie MeSH
- chronická parodontitida komplikace imunologie mikrobiologie patologie MeSH
- cytokiny genetika imunologie MeSH
- dítě MeSH
- dospělí MeSH
- exprese genu MeSH
- koronární nemoc komplikace imunologie mikrobiologie patologie MeSH
- lidé MeSH
- přirozená imunita MeSH
- proteiny teplotního šoku genetika imunologie MeSH
- rizikové faktory MeSH
- zubní plak komplikace imunologie mikrobiologie patologie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- cytokiny MeSH
- proteiny teplotního šoku MeSH
Coronary artery bypass grafting (CABG) is performed with the use of cardiopulmonary bypass (CPB) and cardioplegic arrest (CA) of the heart. The advantage of this technique, alternatively referred to as "on-pump" surgery, resides, for the surgeon, in relatively easy access to and manipulation with the non-beating, bloodless heart. However, the advantage that is, thereby, gained by the patient is paid off by an increased susceptibility to postoperative systemic inflammatory response syndrome (SIRS). Under unfavorable conditions, the inflammatory syndrome may develop into life-threatening forms of MODS (multiple organ dysfunction syndrome) or even MOFS (multiple organ failure syndrome). Deliberate avoidance of CPB, also known as "off-pump" surgery, attenuates early postoperative inflammation throughout its trajectory of SIRS→MODS→MOFS, but, in the long run, there appears to be no substantial difference in the overall mortality rates. In the last years, our knowledge of the pathophysiology of surgical inflammation has increased considerably. Recent findings, highlighting the as yet rather obscure role of pentraxin 3 (PTX3) in these processes, are discussed in this review article.
- Klíčová slova
- alarmins, cardiopulmonary bypass, coronary artery bypass grafting, interleukin-10, pentraxin 3, sterile inflammation,
- MeSH
- antiflogistika imunologie MeSH
- ateroskleróza imunologie MeSH
- C-reaktivní protein genetika imunologie MeSH
- infarkt myokardu imunologie MeSH
- interleukin-10 imunologie MeSH
- kardiopulmonální bypass škodlivé účinky metody MeSH
- koronární bypass škodlivé účinky metody MeSH
- lidé MeSH
- sérový amyloidový protein genetika imunologie MeSH
- syndrom systémové zánětlivé reakce etiologie genetika imunologie MeSH
- transkriptom MeSH
- vyvolaná zástava srdce škodlivé účinky metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- antiflogistika MeSH
- C-reaktivní protein MeSH
- interleukin-10 MeSH
- PTX3 protein MeSH Prohlížeč
- sérový amyloidový protein MeSH