Za mikropartikule (MP) můžeme považovat částice s velikostí 0,05– 1 mm. Jejich složení je značně variabilní dle jejich původu. Vždy však nesou na svém povrchu glykoproteiny exprimované taktéž na povrchu buněk. Této vlastnosti se také využívá k jejich detekci pomocí monoklonálních protilátek. MP se uvolňují jako fragmenty z plazmatické membrány prakticky všech typů eukaryotických buněk po jejich stimulaci nebo v rámci jejich apoptózy. MP se mohou tvořit také při procesu narušení buněčné tkáně. Vznik MP takto může reprezentovat širokou odpověď podněty typu buněčného stimulu nebo stresu. V patogenezi zánětu patří mezi klíčové kroky poškození endotelu a uvolnění membrány mikročástic. Metody detekce MP vychází jednak ze snahy stanovit jejich absolutní počet a jednak stanovit jejich trombogenní potenciál. Pro stanovení počtu MP lze s úspěchem využít průtokovou cytometrii, kdy bylo v poslední době popsáno mnoho metod využívajících široké spektrum monoklonálních protilátek. V současné době se využívají zejména stanovení trombocytárních MP pomocí detekce exprese CD41 znaku a endoteliální MP pomocí CD144 znaku. ELISA metodiky naopak slouží pro stanovení trombogenního potenciálu MP pomocí detekce exprese P- selektinu. Specifi ckou metodou se jeví použití trombin generačního testu v kombinaci s ultrafi ltrací pro stanovení trombogenního potenciálu MP. Patologie spojené s MP vychází zejména z poznání jejich patofyziologických vlastností. Trombogenní potenciál je benefi tem u trombocytopenií, kde vysoké hladiny MP jsou detekovány u pacientů bez krvácivých komplikací. Tato vlastnost však může být příčinou trombotických komplikací. Naopak negativní vliv mohou mít MP u infarktu myokardu, zánětlivých procesů nebo roztroušené sklerózy.
Microparticles (MPs) are particles sized 0.05– 1 mm. Their composition varies considerably depending on their origin. On their surface, however, glycoproteins are always found, that are also expressed on the cell surface. This characteristic is used for their detection using monoclonal antibodies. MPs are released as fragments from the plasma membrane of practically all types of eukaryotic cells, either after their stimulation or during apoptosis. MPs may also be formed in the process of cellular tissue damage. Thus, MP formation may represent a wide response to common stimuli in processes such as cellular stress. Endothelial damage and membrane disruption are the key steps in the pathogenesis of infl ammation. Methods for detecting MPs result from attempts to determine both their absolute count and their thrombogenic potential. To measure the count of MPs, fl ow cytometry may be used with success. Recently, numerous methods using a broad spectrum of monoclonal antibodies have been described. At present, platelet MPs are determined by detecting expression of CD41 and endothelial MPs by expression of CD144. By contrast, ELISA methods are used to evaluate the thrombogenic potential of MPs by detecting expression of P- selectin. A specifi c method is the thrombin generation assay combined with ultrafi ltration to assess the thrombogenic potential of MPs. Understanding the role of MPs in the pathology of numerous diseases is primarily based on the knowledge of their pathophysiological properties. The thrombogenic potential is benefi cial in thrombocytopenia, with high levels of MPs being detected in patients without bleeding complications. However, this feature may cause thrombotic complications. On the other hand, MPs may play a negative role in myocardial infarction, infl ammatory processes or multiple sclerosis.
- Keywords
- generace trombinu, trombofilní riziko,
- MeSH
- Anticoagulants blood therapeutic use MeSH
- Biomarkers blood MeSH
- Endothelium, Vascular enzymology physiopathology pathology MeSH
- Enzyme-Linked Immunosorbent Assay methods utilization MeSH
- Financing, Organized MeSH
- Clinical Laboratory Techniques MeSH
- Humans MeSH
- Membrane Glycoproteins isolation & purification blood MeSH
- Cell-Derived Microparticles classification MeSH
- P-Selectin isolation & purification blood MeSH
- Flow Cytometry methods utilization MeSH
- Selectins isolation & purification blood MeSH
- Thrombin isolation & purification classification MeSH
- Thrombosis enzymology etiology blood MeSH
- Inflammation enzymology etiology blood MeSH
- Check Tag
- Humans MeSH
OBJECTIVES: HIV-infected individuals are at higher risk of non-AIDS diseases associated with procoagulant status. Microparticles are elevated in disorders associated with thrombosis (e.g., cardiovascular diseases). We investigated the association between microparticle levels in untreated and treated HIV-infected subjects, and determined the association with immune status, viral replication, and duration of antiretroviral therapy. PATIENTS AND METHODS: We included 144 HIV-infected subjects, including 123 on antiretroviral therapy (ART) and 21 before treatment initiation. A control group of 40 HIV-negative healthy adults matched for age and sex was used for comparison of microparticle levels. Treated subjects were divided into five groups depending on the period of antiretroviral exposure. Statistically significant differences were determined by Kruskal-Wallis test and Chi2 test. The relation between microparticles and other parameters was assessed using Spearman's coefficient of correlation. RESULTS: Microparticle levels were significantly higher in treated and untreated HIV-infected subjects than in non-HIV-infected controls (P<0.001). The microparticle level was similar between the groups on treatment (P=0.913). No association between the microparticle level and CD4+ count, CD4+/CD8+ ratio, number of HIV-1 RNA copies, or duration of exposure to antiretroviral treatment was observed. CONCLUSION: Increased levels of microparticles may be due to processes independent of viral replication and CD4+ cell count, and microparticle release might persist even during viral suppression by antiretroviral treatment. Elevated microparticle levels might occur in response to other triggers.
- MeSH
- Adult MeSH
- Blood Coagulation * MeSH
- HIV Infections blood MeSH
- Middle Aged MeSH
- Humans MeSH
- Cell-Derived Microparticles * MeSH
- Young Adult MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND/AIM: This work aimed to prospectively evaluate the clinical significance of circulating microparticles (MPs) in relation to thrombotic risk factors and thrombotic complications in patients with BCR/ABL1-negative myeloproliferative neoplasms (MPN). PATIENTS AND METHODS: In a cohort of 206 patients with MPN, MPs' procoagulant activity was measured by the Zymuphen functional assay in 429 samples, while platelet- and erythrocyte-MPs were enumerated by flow cytometry in 558 samples. RESULTS: MPN patients had higher MP levels than the control group. The levels of MPs were higher in male patients, smokers, and those who were older than 60 years, and in the presence of JAK2V617F mutation, history of thrombosis, platelets >400×109/l, hematocrit >45%, or leukocytes >10×109/l. Cytoreductive treatment reduced MP levels, with anagrelide being associated with lower MP levels than hydroxyurea. CONCLUSION: The relationship with thrombotic risk factors indicates a possible role of MPs in the complex thrombotic mechanism, though cytoreductive treatment seems to affect this role through reducing MP levels.
- MeSH
- Humans MeSH
- Cell-Derived Microparticles * MeSH
- Myeloproliferative Disorders * drug therapy genetics MeSH
- Neoplasms * MeSH
- Blood Platelets MeSH
- Thrombosis * etiology genetics MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
Microparticles are small membrane fragments with dimension between 0.1 and 1 μm, which are released during cell activation or apoptosis, exposing the phospholipid phosphatidylserine and membrane antigens typical for cellular origin. Philadelphia-negative myeloproliferative neoplasms (MPNs) are characterized by an increased risk of thrombosis. Data from literature suggest an association between thrombosis and the procoagulant activity of microparticles. Association between the procoagulant activity of microparticles and the incidence of thrombosis was assesed in a group of 126 patients with Philadelphia-negative MPNs. Measurement of microparticles procoagulant activity was performed using a functional assay, namely the Zymuphen MP-activity (Hyphen Biomed, Neuville-sur-oise, France). A total of 539 samples were analysed within this group of patients, regardless of patients' state of health. A significantly higher circulating microparticles procoagulant activity was found in MPN patients as compared with the control group (P < 0.001). A pathological level of procoagulant activity was observed more frequently in patients with polycythaemia vera (88%, P = 0.002) than groups of patients with essential thrombocythaemia (73.2%) and primary myelofibrosis (68.3%); the same result was confirmed in patients with a history of venous thrombosis in comparison with patients without thrombosis (84.7 vs. 73.2%, P = 0.029). Patients without cytoreductive treatment had a higher activity of microparticles (P = 0.010). Furthermore, presence of JAK2 V617F mutation was associated with an increased procoagulant activity (P = 0.007), as well as the higher JAK2 V617F allele burden (P = 0.001). Further prospective clinical studies will be necessary to evaluate the clinical relevance of microparticles in the prediction hypercoagulable state in these patients.
- MeSH
- Incidence MeSH
- Middle Aged MeSH
- Humans MeSH
- Cell-Derived Microparticles pathology MeSH
- Myeloproliferative Disorders blood complications pathology MeSH
- Polycythemia Vera blood complications pathology MeSH
- Thrombosis blood etiology pathology MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Formulace mikročástic složených ze směsi nosičů představuje inovativní přístup pro podání léčiv do plic ve formě suchého prášku. Použité nosiče mohou významně ovlivnit výsledné vlastnosti mikročástic, jako je velikost, tvar, povrch, hygroskopicita či agregace, a tím zlepšit aerosolizaci léčiv po jejich inhalaci. Zmíněné vlastnosti jsou klíčové pro efektivní pulmonální terapii. Kombinací nosičů povahy sacharidů a gelujících látek je výhodné pro řízené uvolňování léčiva. Cílem experimentální práce bylo sprejovým sušením připravit a následně zhodnotit několik šarží mikročástic složených z nosičů na bázi cukrů (manitol, maltodextrin, dextran) a gelujících sacharidů (chitosan, chondroitin-sulfát) a vybrat vhodnou kombinaci pro navazující experimentální práce zaměřené na inkorporaci léčiva do mikročásticové matrice. Nejvhodnější parametry vykazovaly šarže, jejichž aerodynamický průměr se blížil 5 μm, a to částice připravené z kombinace manitolu a dextranu, chitosanu a chondroitinu nebo maltodextrinu a chondoitinu. U těchto šarží byla také naměřena nejvyšší hodnota frakce jemných částic (> 43 %). Z pohledu zpracovatelnosti je vhodná šarže se zastoupením maltodextrinu a chondroitinu vzhledem k nižší viskozitě vstupní disperze a pravidelnějšímu tvaru finálních mikročástic.
The formulation of microparticles composed of a mixture of carriers represents an innovative approach for lung drug delivery of dry powder. The carriers used can significantly influence the properties of the microparticles, such as size, shape, surface area, hygroscopicity, or aggregation, thus improving the aerosolization of the drugs after inhalation. The properties mentioned above are crucial for effective pulmonary therapy. The combination of carriers of a carbohydrate nature and gelling agents is advantageous for controlled drug release. The experimental work aimed to prepare by spray drying and subsequently evaluate ten batches of microparticles composed of sugar-based carriers (mannitol, maltodextrin, dextran) and gelling polymers (chitosan, chondroitin sulfate) and to select a suitable combination for follow-up experimental work aimed at drug incorporation into the microparticle matrix. The most suitable parameters were exhibited by batches whose aerodynamic diameter was close to 5 μm, particles prepared from a combination of mannitol and dextran, chitosan and chondroitin, or maltodextrin and chondroitin. These batches also showed the highest fine particle fraction value (> 43%). From a processability point of view, the batch with maltodextrin and chondroitin is preferable due to the lower viscosity of the dispersion and the more regular shape of the final microparticles.
- MeSH
- Administration, Inhalation MeSH
- Pharmaceutical Research MeSH
- Humans MeSH
- Microplastics MeSH
- Drug Carriers * MeSH
- Spray Drying MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
Endothelial-derived microparticles (EMPs) are a novel biological marker of endothelium injury and vasomotion disorders that are involved in pathogenesis of cardiovascular, metabolic, and inflammatory diseases. Circulating levels of EMPs are thought to reflect a balance between cell stimulation, proliferation, apoptosis, and cell death. Increased EMPs may be defined in several cardiovascular diseases, such as stable and unstable coronary artery disease, acute and chronic heart failure, hypertension, arrhythmias, thromboembolism, asymptomatic atherosclerosis as well as renal failure, metabolic disorders (including type two diabetes mellitus, abdominal obesity, metabolic syndrome, insulin resistance) and dyslipidemia. This review highlights the controversial opinions regarding impact of circulating EMPs in major cardiovascular and metabolic diseases and summarizes the perspective implementation of the EMPs in risk stratification models.
- MeSH
- Biomarkers MeSH
- Endothelium, Vascular physiology MeSH
- Kidney Failure, Chronic blood MeSH
- Diabetes Mellitus blood MeSH
- Risk Assessment MeSH
- Cardiovascular Diseases blood diagnosis epidemiology MeSH
- Humans MeSH
- Metabolic Syndrome blood MeSH
- Cell-Derived Microparticles physiology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Left ventricular assist devices (LVAD), currently used in treatment of terminal heart failure, are working on principle of rotary pump, which generates continuous blood flow. Non-pulsatile flow is supposed to expose endothelial cells to high stress and potential damage. Therefore, we investigated longitudinal changes in concentration of circulating endothelial microparticles (EMP) as a possible marker of endothelial damage before and after implantation of LVAD. Study population comprised 30 patients with end-stage heart failure indicated for implantation of the Heart Mate II LVAD. Concentrations of microparticles were measured as nanomoles per liter relative to phosphatidylserine before and 3 months after implantation. At 3 months after implantation we observed significant decrease in concentration of EMP [5.89 (95 % CI 4.31-8.03) vs. 3.69 (95 % CI 2.70-5.03), p=0.03] in the whole group; there was no difference observed between patients with ischemic etiology of heart failure (n=18) and with heart failure of non-ischemic etiology (n=12). In addition, heart failure etiology had no effect on the rate of EMP concentration decrease with time. These results indicate possibility that LVAD do not cause vascular damage 3 months after implantation. Whether these results suggest improvement of vascular wall function and of endothelium is to be proved in long-term studies.
- MeSH
- Endothelium, Vascular metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- Longitudinal Studies MeSH
- Cell-Derived Microparticles metabolism MeSH
- Heart-Assist Devices * trends MeSH
- Aged MeSH
- Heart Failure blood diagnosis surgery MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: Microparticles (MPs) are heterogeneous vesicles derived from membranes of different cells. Between 70 to 90% of MPs detected in blood originate from platelets. The release of MPs is associated with proinflammatory and procoagulant states. Elevated levels of MPs have been found in different diseases. We investigated MPs levels in patients with chronic hepatitis C (CHC) and changes in level during treatment using direct-acting antivirotics (DAA). PATIENTS AND METHODS: Thirty-six patients with CHC and forty healthy volunteers were included in the study. Concentrations of MPs were determined indirectly by measuring their procoagulant activity in plasma at baseline, end of therapy (EOT), and 12 weeks after EOT when the sustained virological response was assessed (SVR12). RESULTS: All patients achieved SVR12, which was associated with rapid improvement of markers of liver damage and function as well as liver stiffness (P=0.002). MPs levels were significantly higher in CHC patients than in healthy volunteers (P<0.001). No statistically significant decrease was found observed between baseline and SVR12 (P=0,330). Analysis of subpopulations with minimal fibrosis F0-1 (P=0.647), advanced fibrosis F2-4 (P=0.370), women(P=0.847), men (P=0.164) and genotype 1 (P=0.077) showed no significant changes during the follow-up period. CONCLUSIONS: MPs levels are higher in CHC patients and remain elevated shortly after achieving SVR. Higher concentrations of MPs in plasma are probably caused by a chronic uncontrolled exaggerated inflammatory response caused by CHC. Longer observation would probably confirm the significance of MPs levels decrease because normalization of liver function, inflammation, and structure after SVR requires more than 12 weeks.
- MeSH
- Antiviral Agents therapeutic use MeSH
- Hepatitis C, Chronic * drug therapy MeSH
- Fibrosis MeSH
- Liver Cirrhosis drug therapy MeSH
- Humans MeSH
- Cell-Derived Microparticles * MeSH
- Sustained Virologic Response MeSH
- Inflammation MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Microparticles are small circulating vesicles originating from circulatory system and vascular wall cells released during their activation or damage. They possess different roles in regulation of endothelial function, inflammation, thrombosis, angiogenesis, and in general, cellular stress. Microparticles are the subject of intensive research in pulmonary hypertension, atherosclerotic disease, and heart failure. Another recently emerging role is the evaluation of the status of vasculature in end-stage heart failure patients treated with implantable ventricular assist devices. In patients implanted as destination therapy, assessment of the long-term effect of currently used continuous-flow left ventricular assist devices (LVADs) on vasculature might be of critical importance. However, unique continuous flow pattern generated by LVADs makes it difficult to assess reliably the vascular function with most currently used methods, based mainly on ultrasound detection of changes of arterial dilatation during pulsatile flow. In this respect, the measurement of circulating microparticles as a marker of vascular status may help to elucidate both short- and long-term effects of LVADs on the vascular system. Because data regarding this topic are very limited, this review is focused on the advantages and caveats of the circulating microparticles as markers of vascular function in patients on continuous-flow LVADs.
- MeSH
- Biomarkers blood MeSH
- Humans MeSH
- Cell-Derived Microparticles * MeSH
- Vascular Diseases diagnosis etiology MeSH
- Heart-Assist Devices adverse effects MeSH
- Heart Failure therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
