Exposures to social and environmental stressors arise individual behavioural response and thus indirectly affect cardiometabolic health. The aim of this study was to investigate several social and environmental stressors and the paths of their influence on cardiometabolic health. The data of 2154 participants (aged 25-64 years) from the cross-sectional population-based study were analysed. The composite score of metabolic disorders (MS score) was calculated based on 5 biomarkers: waist circumference, blood pressure, fasting blood glucose, HDL-cholesterol, triglycerides. The effects of social stressors (education level, income), environmental stressors (NO2, noise) and behavioural factors (unhealthy diet, smoking, alcohol consumption, sedentary behaviours) on MS score were assessed using a structural model. We observed a direct effect of education on MS score, as well as an indirect effect mediated via an unhealthy diet, smoking, and sedentary behaviours. We also observed a significant indirect effect of income via sedentary behaviours. The only environmental stressor predicting MS was noise, which also mediated the effect of education. In summary, the effect of social stressors on the development of cardiometabolic risk had a higher magnitude than the effect of the assessed environmental factors. Social stressors lead to an individual's unhealthy behaviour and might predispose individuals to higher levels of environmental stressors exposures.
- MeSH
- biologické markery krev MeSH
- dospělí MeSH
- HDL-cholesterol krev MeSH
- kardiovaskulární nemoci etiologie epidemiologie MeSH
- kouření škodlivé účinky MeSH
- krevní glukóza metabolismus MeSH
- krevní tlak MeSH
- lidé středního věku MeSH
- lidé MeSH
- metabolické nemoci etiologie epidemiologie MeSH
- obvod pasu MeSH
- průřezové studie MeSH
- psychický stres MeSH
- rizikové faktory MeSH
- sedavý životní styl * MeSH
- triglyceridy krev MeSH
- vystavení vlivu životního prostředí škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The thermo- and pain-sensitive Transient Receptor Potential Melastatin 3 and 8 (TRPM3 and TRPM8) ion channels are functionally associated in the lipid rafts of the plasma membrane. We have already described that cholesterol and sphingomyelin depletion, or inhibition of sphingolipid biosynthesis decreased the TRPM8 but not the TRPM3 channel opening on cultured sensory neurons. We aimed to test the effects of lipid raft disruptors on channel activation on TRPM3- and TRPM8-expressing HEK293T cells in vitro, as well as their potential analgesic actions in TRPM3 and TRPM8 channel activation involving acute pain models in mice. CHO cell viability was examined after lipid raft disruptor treatments and their effects on channel activation on channel expressing HEK293T cells by measurement of cytoplasmic Ca2+ concentration were monitored. The effects of treatments were investigated in Pregnenolone-Sulphate-CIM-0216-evoked and icilin-induced acute nocifensive pain models in mice. Cholesterol depletion decreased CHO cell viability. Sphingomyelinase and methyl-beta-cyclodextrin reduced the duration of icilin-evoked nocifensive behavior, while lipid raft disruptors did not inhibit the activity of recombinant TRPM3 and TRPM8. We conclude that depletion of sphingomyelin or cholesterol from rafts can modulate the function of native TRPM8 receptors. Furthermore, sphingolipid cleavage provided superiority over cholesterol depletion, and this method can open novel possibilities in the management of different pain conditions.
- MeSH
- analgetika farmakologie terapeutické užití MeSH
- beta-cyklodextriny * farmakologie MeSH
- bolest chemicky indukované farmakoterapie metabolismus MeSH
- CHO buňky MeSH
- cholesterol metabolismus MeSH
- Cricetulus MeSH
- HEK293 buňky MeSH
- kationtové kanály TRPM * metabolismus genetika MeSH
- lidé MeSH
- membránové mikrodomény metabolismus účinky léků MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- pregnenolon farmakologie MeSH
- pyrimidinony farmakologie MeSH
- sfingomyelinfosfodiesterasa * metabolismus farmakologie MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Metabolický syndrom nadále představuje jednu z nejčastějších klinických situací asociovaných se zvýšením kardiometa- bolického rizika v Česku. Dyslipidemie nacházená u pacientů s metabolickým syndromem je hlavním nositelem zvýšené- ho rizika aterotrombotických komplikací. Nefarmakologická opatření zlepšují kromě dyslipidemie také všechny ostatní složky metabolického syndromu. Jejich prosazení je nesnadné a farmakoterapie by zejména u osob ve vysokém a velmi vysokém kardiovaskulárním riziku neměla být odkládána. Hypolipidemická léčba u osob s metabolickým syndromem má být založena na statinu, případně v kombinaci s ezetimibem. U statin intolerantních můžeme nově využívat kyselinu bempedoovou. Fenofibrát může být použit u konkrétních pacientů, je třeba otestovat jeho vliv na koncentrace non-HDL-C a apolipoproteinu B u konkrétního léčeného. Využití omega-3 mastných kyselin v našich podmínkách není relevantní, jediný prokazatelně účinný přípravek (ethyl ester eikosapentaenové kyseliny) není v Česku dostupný. PCSK9 terapie pomohou dosáhnout cílových hodnot i u obtížně léčitelných pacientů v kategoriích vysokého nebo velmi vysokého rizika.
Metabolic syndrome continues to represent one of the most common clinical situations associated with increased cardiometabolic risk in the Czech Republic. Dyslipidemia found in patients with metabolic syndrome is the main carrier of increased risk of atherothrombotic complications. Non-pharmacological measures improve all other components of the metabolic syndrome in addition to dyslipidemia. Their enforcement is difficult and pharmacotherapy should not be postponed, especially in persons at high and very high cardiovascular risk. Hypolipidemic treatment in people with metabolic syndrome should be based on a statin, possibly in combination with ezetimibe. For those intolerant to statins, we can now use bempedoic acid. Fenofibrate can be used in specific patients, it is necessary to test its effect on the concentrations of non-HDL-C and apolipoprotein B in a specific patient. The use of omega-3 fatty acids in our conditions is not relevant, the only demonstrably effective preparation (ethyl ester of eicosapentaenoic acid) is not available in the Czech Republic. PCSK9 therapies will help achieve target values even in difficult-to-treat patients in the high or very high risk categories.
- MeSH
- apolipoproteiny B analýza MeSH
- cholesterol analýza MeSH
- dyslipidemie * etiologie farmakoterapie patofyziologie terapie MeSH
- látky regulující metabolismus lipidů aplikace a dávkování farmakologie klasifikace MeSH
- lidé MeSH
- metabolický syndrom * farmakoterapie patologie terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- časná diagnóza MeSH
- dítě MeSH
- hyperlipoproteinemie typ II * diagnóza farmakoterapie MeSH
- kongresy jako téma MeSH
- LDL-cholesterol analýza škodlivé účinky MeSH
- lidé MeSH
- náchylnost k nemoci MeSH
- plošný screening metody MeSH
- rizikové faktory MeSH
- statiny terapeutické užití MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- novinové články MeSH
- zprávy MeSH
INTRODUCTION: Benzotriazoles and benzothiazoles (BTs) are high-production volume chemicals as well as widely distributed emerging pollutants with potential health risk. However, information about human exposure to BTs and associated health outcomes is limited. OBJECTIVE: We aimed to characterise exposure to BTs among Czech men, including possible occupational exposure among firefighters, its predictors, and its associations with liver function, serum lipids and oxidative stress. METHODS: 165 participants (including 110 firefighters) provided urine and blood samples that were used to quantify the urinary levels of 8 BTs (high-performance liquid chromatography-tandem mass spectrometry), and 4 liver enzymes, cholesterol, low-density lipoprotein, and 8-hydroxy-2'-deoxyguanosine. Linear regression was used to assess associations with population characteristics and biomarkers of liver function, serum lipids and oxidative stress. Regression models were adjusted for potential confounding variables and false discovery rate procedure was applied to account for multiplicity. RESULTS: The BTs ranged from undetected up to 46.8 ng/mL. 2-hydroxy-benzothiazole was the most predominant compound (detection frequency 83%; median 1.95 ng/mL). 1-methyl-benzotriazole (1M-BTR) was measured in human samples for the first time, with a detection frequency 77% and median 1.75 ng/mL. Professional firefighters had lower urinary 1M-BTR compared to non-firefighters. Urinary 1M-BTR was associated with levels of γ-glutamyl transferase (β = - 17.54%; 95% CI: - 26.127, - 7.962). CONCLUSION: This is the first study to investigate BT exposure in Central Europe, including potentially exposed firefighters. The findings showed a high prevalence of BTs in the study population, the relevance of 1M-BTR as a new biomarker of exposure, and an urgent need for further research into associated adverse health outcomes.
- MeSH
- 8-hydroxy-2'-deoxyguanosin moč krev MeSH
- benzothiazoly * MeSH
- biologické markery * krev moč MeSH
- cholesterol krev MeSH
- deoxyguanosin analogy a deriváty moč krev MeSH
- dospělí MeSH
- hasiči MeSH
- játra účinky léků MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipidy krev MeSH
- oxidační stres * účinky léků MeSH
- pracovní expozice * analýza MeSH
- triazoly * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
Liposomal carrier systems have emerged as a promising technology for pulmonary drug delivery. This study focuses on two selected liposomal systems, namely, dipalmitoylphosphatidylcholine stabilized by phosphatidic acid and cholesterol (DPPC-PA-Chol) and dipalmitoylphosphatidylcholine stabilized by polyethylene glycol and cholesterol (DPPC-PEG-Chol). First, the research investigates the stability of these liposomal systems during the atomization process using different kinds of nebulizers (air-jet, vibrating mesh, and ultrasonic). The study further explores the aerodynamic particle size distribution of the aerosol generated by the nebulizers. The nebulizer that demonstrated optimal stability and particle size was selected for more detailed investigation, including Andersen cascade impactor measurements, an assessment of the influence of flow rate and breathing profiles on aerosol particle size, and an in vitro deposition study on a realistic replica of the upper airways. The most suitable combination of a nebulizer and liposomal system was DPPC-PA-Chol nebulized by a Pari LC Sprint Star in terms of stability and particle size. The influence of the inspiration flow rate on the particle size was not very strong but was not negligible either (decrease of Dv50 by 1.34 μm with the flow rate increase from 8 to 60 L/min). A similar effect was observed for realistic transient inhalation. According to the in vitro deposition measurement, approximately 90% and 70% of the aerosol penetrated downstream of the trachea using the stationary flow rate and the realistic breathing profile, respectively. These data provide an image of the potential applicability of liposomal carrier systems for nebulizer therapy. Regional lung drug deposition is patient-specific; therefore, deposition results might vary for different airway geometries. However, deposition measurement with realistic boundary conditions (airway geometry, breathing profile) brings a more realistic image of the drug delivery by the selected technology. Our results show how much data from cascade impactor testing or estimates from the fine fraction concept differ from those of a more realistic case.
- MeSH
- 1,2-dipalmitoylfosfatidylcholin MeSH
- aerosoly MeSH
- aplikace inhalační MeSH
- bronchodilatancia * MeSH
- cholesterol MeSH
- design vybavení MeSH
- lidé MeSH
- liposomy MeSH
- nebulizátory a vaporizátory MeSH
- systémy cílené aplikace léků MeSH
- trachea * MeSH
- velikost částic MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
CD36/FAT (translokáza mastných kyselin) hraje centrální roli v kardiovaskulárních onemocněních, má nezměněnou strukturu u různých živočišných druhů. Jeho vyjádření v tukové tkáni, kosterním svalu, játrech a makrofázích arteriální stěny zdůrazňuje tento význam. Kromě fagocytace oxidovaných LDL (oxLDL) receptor CD36 akceleruje prozánětlivý proces v celém organismu. Specificita mikroprostředí tukové tkáně s vysokou koncentrací volných mastných kyselin, inzulinu a glukózy indukuje polarizaci specifickými metabolickými cestami k produkci metabolicky aktivovaných prozánětlivých makrofágů (MAPIM) s výraznou expresí CD36. Proporce MAPIM v lidské tukové tkáni výrazně koreluje se dvěma hlavními rizikovými faktory kardiovaskulárních nemocí – hypercholesterolemií a obezitou. Polarizace MAPIM v tukové tkáni je dána složením mastných kyselin fosfolipidů celulární membrány a vzrůstá s proporcí palmitátu a palmitooleátu a naopak klesá s proporcí n-3 mastných kyselin, zejména kyseliny -linolenové a eikosapentaenové. Při analýze tohoto vlivu odděleně v adipocytech a makrofázích jsme prokázali, že adipocyty tvoří vhodné mikroprostředí polarizace (s podobnými vztahy k mastným kyselinám celulární membrány). Naproti tomu polarizace vlastních makrofágů je určena kompeticí nasyceného palmitátu a cholesterolových molekul v raftu celulární membrány. CD36 hraje klíčovou roli v rozvoji aterosklerózy pohlcováním oxLDL, tvorbou tukových proužků a pěnových buněk až ke vzniku komplikovaných lézí. Nedostatek receptorů CD36 brzdí aterogenní proces jak v experimentu, tak u osob s jeho genetickým snížením. Komplexní role CD36 v zánětu, lipidovém metabolismu a angiogenezi hraje klíčovou roli v celulární a orgánové komunikaci s aktivací aterogenního procesu.
The CD36/FAT (fatty acid translocator) receptor is a crucial player in cardiovascular diseases, featuring a consistent structure across species. Its expression in adipose tissue, skeletal muscle, liver, and arterial wall macrophages underscores its importance. Beyond scavenging oxidized LDL (oxLDL), CD36 accelerates the pro-inflammatory processes in all these organs. Specific microenvironments of adipose tissue with high concentrations of free long-chain fatty acids, insulin, and glucose induce polarization by tissue-specific path- ways producing metabolically activated pro-inflammatory macrophages (MAPIMs) with high CD36 expres- sion. The proportion of MAPIMs in human adipose tissue correlates significantly with the two main risk predictors of cardiovascular diseases - hypercholesterolemia and obesity. Polarization of MAPIMs in adipose tissue is defined by the fatty acid composition of cell membrane phospholipids, and increases with the proportion of palmitic, and mainly palmitoleate, fatty acids and decreases with the presence of n-3 polyenic fatty acids, specifically α-linolenic and eicosapentaenoic fatty acids. When analysing this effect separately for adipocytes and macrophages, we found that adipocytes create a microenvironment (with a relationship similar to the effects of individual fatty acids of membrane phospholipids) beneficial for pro-inflammatory polarization. On the contrary, macrophage polarization is related to the competition of unsaturated palmitate and cholesterol molecules in the membrane raft. CD36 is crucial for the development of atherosclerosis within the arterial wall, scavenging oxLDL producing fatty streaks and foam cells until the formation of complicated atherosclerotic lesions. CD36 deficiency attenuates atherosclerotic lesion development both in experimental models and individuals with genetic defects of this receptor. The complex role of CD36 in inflammation, lipid metabolism, and angiogenesis makes it a key player in cell- and organ-level communication, activating the atherogenic process.
PURPOSE OF REVIEW: Chronic kidney disease (CKD) is associated with a significantly increased risk of cardiovascular disease (CVD). This review summarizes known risk factors, pathophysiological mechanisms, and current therapeutic possibilities, focusing on lipid-lowering therapy in CKD. RECENT FINDINGS: Novel data on lipid-lowering therapy in CKD mainly stem from clinical trials and clinical studies. In addition to traditional CVD risk factors, patients with CKD often present with non-traditional risk factors that include, e.g., anemia, proteinuria, or calcium-phosphate imbalance. Dyslipidemia remains an important contributing CVD risk factor in CKD, although the mechanisms involved differ from the general population. While statins are the most commonly used lipid-lowering therapy in CKD patients, some statins may require dose reduction. Importantly, statins showed diminished beneficial effect on cardiovascular events in patients with severe CKD and hypercholesterolemia despite high CVD risk and effective reduction of LDL cholesterol. Ezetimibe enables the reduction of the dose of statins and their putative toxicity and, in combination with statins, reduces CVD endpoints in CKD patients. The use of novel drugs such as PCSK9 inhibitors is safe in CKD, but their potential to reduce cardiovascular events in CKD needs to be elucidated in future studies.
- MeSH
- anticholesteremika * terapeutické užití MeSH
- chronická renální insuficience * komplikace epidemiologie MeSH
- kardiovaskulární nemoci * epidemiologie etiologie prevence a kontrola MeSH
- LDL-cholesterol MeSH
- lidé MeSH
- proproteinkonvertasa subtilisin/kexin typu 9 MeSH
- rizikové faktory kardiovaskulárních chorob MeSH
- rizikové faktory MeSH
- statiny * terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
BACKGROUND: Despite a general decline in mean levels across populations, LDL-cholesterol levels remain a major risk factor for acute coronary syndrome (ACS). The APOB, LDL-R, CILP, and SORT-1 genes have been shown to contain variants that have significant effects on plasma cholesterol levels. METHODS AND RESULTS: We examined polymorphisms within these genes in 1191 controls and 929 patients with ACS. Only rs646776 within SORT-1 was significantly associated with a risk of ACS (P < 0.05, AA vs. + G comparison; OR 1.21; 95% CI 1.01-1.45). With regard to genetic risk score (GRS), the presence of at least 7 alleles associated with elevated cholesterol levels was connected with increased risk (P < 0.01) of ACS (OR 1.26; 95% CI 1.06-1.52). Neither total mortality nor CVD mortality in ACS subjects (follow up-9.84 ± 3.82 years) was associated with the SNPs analysed or cholesterol-associated GRS. CONCLUSIONS: We conclude that, based on only a few potent SNPs known to affect plasma cholesterol, GRS has the potential to predict ACS risk, but not ACS associated mortality.
- MeSH
- akutní koronární syndrom * genetika MeSH
- cholesterol MeSH
- genetické rizikové skóre * MeSH
- jednonukleotidový polymorfismus genetika MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
