Capillary functions in vascular diseases
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Capillary functions in humans can be assessed by measuring capillary filtration and capillary diffusion capacity in the extremities. Examination of these two parameters supplements each other and renders it possible to evaluate capillary function from different aspects. As an example of practical use may serve the findings in patients with obliterating atherosclerosis of the lower extremities and in subjects with chronic venous insufficiency. The authors revealed a rised capillary diffussion capacity on obliterated extremities and a reduced capillary filtration in venous insufficiency. It is possible that in both instances these are manifestations of adaptational changes focused on the prevention of oedema formation and on a raised metabolism under conditions of an inadequate blood supply of tissues.
- MeSH
- arterioskleróza patofyziologie MeSH
- bérec krevní zásobení MeSH
- chronická nemoc MeSH
- kapilární permeabilita * MeSH
- kapiláry fyziologie MeSH
- lidé MeSH
- žilní insuficience patofyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The term "microcirculation" refers to the terminal vascular network of the body, which includes arterioles, capillaries, venules as well as initial lymphatic vessels. Additionally, it insinuates to their unique function in thermoregulation, fluid balance, maintenance of cellular exchange, and metabolism. Disturbances of microvascular function were identified to precede macrovascular involvement in the presence of cardiovascular risk factors and is the hallmark of terminal disease stages like critical limb or acral ischemia. Nevertheless, despite its obvious significance in vascular medicine assessment of microvascular function became increasingly neglected in the clinical institutions during the last decades and seems to play a subordinary role in medical education. We therefore provide an overview over relevant and clinically practicable methods to assess microcirculation in vascular medicine with critical estimations of their pros and cons and their perspectives in the future.
- Klíčová slova
- Capillary microscopy, O2C, indocianine green fluorescence angiography, laser speckled contrast analyzer, tcpO2,
- MeSH
- arterioly MeSH
- kapiláry MeSH
- lidé MeSH
- mikrocirkulace MeSH
- nemoci cév * MeSH
- venuly MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
In connection with the increasing importance of the endothelium in understanding the pathogenesis of vascular diseases, new types of mediators originating in the endothelium are described, such as EDRF and endothelin. The method of endothelial cell cultivation has contributed to their detection. Besides such analytical methods, a more global in vivo aspect of endothelial function is dealt with by the method of counting circulating endothelial cell carcasses in blood applicable also clinically. The increase of endothelaemia goes hand in hand with both the tendency to thrombosis and increased permeability. Similarly, the main atherosclerotic risk factors, smoking, hypertension and hypercholesterolaemia could be effective by producing an endothelial perturbation as indicated by increased endothelaemia.
- MeSH
- arterioskleróza etiologie MeSH
- cévní endotel fyziologie MeSH
- kapilární permeabilita MeSH
- lidé MeSH
- modely kardiovaskulární MeSH
- trombocyty fyziologie MeSH
- trombóza etiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Adiponectin (APN), an adipose tissue-excreted adipokine, plays protective roles in metabolic and cardiovascular diseases. In this study, the effects and mechanisms of APN on biological functions of rat vascular endothelial progenitor cells (VEPCs) were investigated in vitro. After administrating APN in rat VEPCs, the proliferation was measured by methyl thiazolyl tetrazolium (MTT) method, the apoptotic rate was test by Flow cytometry assay, mRNA expression of B-cell lymphoma-2 (Bcl-2) and vascular endothelial growth factor (VEGF) was determined by real-time reverse transcriptase polymerase chain reaction (RT-PCR), and protein expression of mechanistic target of rapamycin (mTOR), signal transducer and activator of transcription 3 (STAT3) and phospho-STAT3 (pSTAT3) was analyzed by Western blot. It was suggested that APN promoted the optical density (OD) value of VEPCs, enhanced mRNA expression of Bcl-2 and VEGF, and inhibited cell apoptotic rate. Furthermore, protein expression of pSTAT3 was also increased in the presence of APN. Moreover, APN changed-proliferation, apoptosis and VEGF expression of VEPCs were partially suppressed after blocking the mTOR-STAT3 signaling pathway by the mTOR inhibitor XL388. It was indicated that APN promoted biological functions of VEPCs through targeting the mTOR-STAT3 signaling pathway.
- MeSH
- adiponektin farmakologie MeSH
- buněčné linie MeSH
- cévní endotel účinky léků metabolismus MeSH
- endoteliální progenitorové buňky účinky léků fyziologie MeSH
- krysa rodu Rattus MeSH
- proliferace buněk účinky léků fyziologie MeSH
- signální transdukce účinky léků fyziologie MeSH
- sulfony farmakologie MeSH
- TOR serin-threoninkinasy antagonisté a inhibitory biosyntéza MeSH
- transkripční faktor STAT3 antagonisté a inhibitory biosyntéza MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- adiponektin MeSH
- mTOR protein, rat MeSH Prohlížeč
- Stat3 protein, rat MeSH Prohlížeč
- sulfony MeSH
- TOR serin-threoninkinasy MeSH
- transkripční faktor STAT3 MeSH
- XL388 MeSH Prohlížeč
The basic physiological functions of the endothelium are functions of a semipermeable membrane, control of optimal vascular patency and safeguarding of the vascular integrity. Endothelial dysfunction may be considered the first functionally important stage of atherosclerosis. The most frequent evoking factors include hyperlipoproteinaemia, arterial hypertension, smoking and diabetes mellitus. The clinically most important manifestations of impaired endothelial function are disorders in the coronary circulation and transient cerebral ischaemias. Ways of detection of endothelial dysfunctions include invasive methods and at present non-invasive ultrasonic methods. Treatment of endothelial dysfunction is based on elimination of the basic risk factors of atherosclerosis, i.e. elimination of active and passive smoking, in indicated cases strict dietetetic and pharmacological hypolipidaemic treatment, effective antihypertensive treatment and compensation of DM.
- MeSH
- arterioskleróza patofyziologie terapie MeSH
- cévní endotel fyziologie patofyziologie MeSH
- diabetické angiopatie patofyziologie MeSH
- hypertenze patofyziologie MeSH
- lidé MeSH
- nemoci cév diagnóza terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- přehledy MeSH
Ultrastructural study of skin biopsies in two cases of Gaucher disease (GD) patients (types II and III) revealed hitherto unknown alteration of the blood capillary endothelial cells (ECs) featured by hypertrophy and numerous subplasmalemmal microvesicles underneath both the apical and basal membranes. There was also prominent apical membrane folding with formation of filiform and large cytoplasmic projections, with occasional transcapillary cytoplasmic bridges. Similar, though less frequently expressed, changes were manifested at the basal membrane by numerous cytoplasmic projections into the subendothelial space. Regressive changes with EC breakdown were rare. Lysosomal storage was always absent. Besides EC hypertrophy, there was also increased EC density in the capillary lumen, leading to pronounced changes in capillary architecture with loose or incomplete EC anchoring. There were also signs of EC sprouting. Some pericytes displayed an increase in size and number of cytoplasmic processes, which often extended into distant pericapillary regions. The spectrum of changes suggests that a significant positive growth effect on EC occurs in GD. The putative mechanisms triggered by GBA1 deficiency leading to EC involvement are discussed. The authors are well aware of the fact the results, based on a nontraditional type of bioptic samples, are preliminary, but they are worth following, as further ultrastructural and functional studies of blood endothelium in GD may open a novel field in molecular cell pathophysiology of the disorder: endothelial dysfunction.
- MeSH
- biopsie metody MeSH
- cévní endotel diagnostické zobrazování patologie MeSH
- cytoplazma metabolismus MeSH
- fibroblasty metabolismus MeSH
- Gaucherova nemoc diagnostické zobrazování patologie MeSH
- kapiláry diagnostické zobrazování patologie MeSH
- kojenec MeSH
- kůže krevní zásobení diagnostické zobrazování patologie MeSH
- lidé MeSH
- lyzozomy metabolismus MeSH
- patologická angiogeneze MeSH
- pericyty metabolismus MeSH
- předškolní dítě MeSH
- ultrasonografie MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
The endothelium is the largest autocrine and endocrine organ of the human organism. It participates in the regulation of the blood flow and tonus of the vascular wall, activation of thrombocytes, adhesion of monocytes to the vascular wall, thrombogenesis, lipid metabolism and growth of vessels. Endothelial cells may produce some 25 different biologically active substances. The most important one among them is probably NO. Under physiological conditions endothelial cells release permanently a small amount of NO or EDRF (endothelium-derived relaxing factor) and participate thus in the regulation of the tonus of the vascular wall at rest. The presence of NO excreated by endothelial cells can be detected in all parts of the circulation, from large arteries to small capillaries. Increased NO excretion is caused by a number of physiological stimuli, e.g. a rise of the blood pressure, drop of the partial oxygen pressure or the action of acetylcholine, ADP, ATP, thrombin, bradykinin or histamine. NO is a chemical messenger which is formed during oxidation of L-arginine to L-citrullin by the action of the enzyme NO synthase (NOS). Endothelial NOS is described as eNOS (endothelial/Type III/NOS-3). There exist also two other different isoforms of this enzyme: nNOS (neuronal/Type I/NOS-1/bNOS) andiNOS (inducible/Type II/NOS-2. NO plays an important part on the regulation of vascular homeostasis. It has a number of potential antiatherogenic functions. It causes vascular vasodilatation.
- MeSH
- arterioskleróza patofyziologie MeSH
- cévní endotel metabolismus fyziologie MeSH
- cévní rezistence fyziologie MeSH
- cévy fyziologie patofyziologie MeSH
- homeostáza * MeSH
- lidé MeSH
- nemoci cév patofyziologie MeSH
- oxid dusnatý metabolismus fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- oxid dusnatý MeSH
The aim of the study was to examine the effect of previous pregnancies and classical cardiovascular risk factors on vascular endothelial function in a group of 264 young and middle-aged women 3 to 11 years postpartum. We examined microvascular functions by peripheral arterial tonometry and EndoPAT 2000 device with respect to a history of gestational hypertension, preeclampsia, fetal growth restriction, the severity of the disease with regard to the degree of clinical signs and delivery date. Besides, we compared Reactive Hyperemia Index (RHI) values and the prevalence of vascular endothelial dysfunction among the groups of women with normal and abnormal values of BMI, waist circumference, systolic and diastolic blood pressures, heart rate, total serum cholesterol levels, serum high-density lipoprotein cholesterol levels, serum low-density lipoprotein cholesterol levels, serum triglycerides levels, serum lipoprotein A levels, serum C-reactive protein levels, serum uric acid levels, and plasma homocysteine levels. Furthermore, we determined the effect of total number of pregnancies and total parity per woman, infertility and blood pressure treatment, presence of trombophilic gene mutations, current smoking of cigarettes, and current hormonal contraceptive use on the vascular endothelial function. We also examined the association between the vascular endothelial function and postpartum whole peripheral blood expression of microRNAs involved in pathogenesis of cardiovascular/cerebrovascular diseases (miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-92a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-155-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-210-3p, miR-221-3p, miR-342-3p, miR-499a-5p, and miR-574-3p). A proportion of overweight women (17.94% and 20.59%) and women with central obesity (18.64% and 21.19%) had significantly lower RHI values at 10.0% false positive rate (FPR) both before and after adjustment of the data for the age of patients. At 10.0% FPR, a proportion of women with vascular endothelial dysfunction (RHI ≤ 1.67) was identified to have up-regulated expression profile of miR-1-3p (11.76%), miR-23a-3p (17.65%), and miR-499a-5p (18.82%) in whole peripheral blood. RHI values also negatively correlated with expression of miR-1-3p, miR-23a-3p, and miR-499a-5p in whole peripheral blood. Otherwise, no significant impact of other studied factors on vascular endothelial function was found. We suppose that screening of these particular microRNAs associated with vascular endothelial dysfunction may help to stratify a highly risky group of young and middle-aged women that would benefit from early implementation of primary prevention strategies. Nevertheless, it is obvious, that vascular endothelial dysfunction is just one out of multiple cardiovascular risk factors which has only a partial impact on abnormal expression of cardiovascular and cerebrovascular disease associated microRNAs in whole peripheral blood of young and middle-aged women.
- Klíčová slova
- cardiovascular risk factors, fetal growth restriction, gestational hypertension, microRNA, peripheral arterial tonometry, preeclampsia, pregnancy-related complications, screening, vascular endothelial function, whole peripheral blood,
- MeSH
- cévní endotel patofyziologie MeSH
- dospělí MeSH
- epigeneze genetická * MeSH
- kardiovaskulární nemoci krev genetika MeSH
- komplikace těhotenství krev genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- logistické modely MeSH
- mikro RNA genetika metabolismus MeSH
- mladý dospělý MeSH
- obezita genetika patofyziologie MeSH
- rizikové faktory MeSH
- těhotenství MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- mikro RNA MeSH
According to the World Health Organization, cardiovascular diseases are the main cause of death worldwide. They may be caused by various factors or combinations of factors. Frequently, endothelial dysfunction is involved in either development of the disorder or results from it. On the other hand, the endothelium may be disordered for other reasons, e.g., due to infection, such as COVID-19. The understanding of the role and significance of the endothelium in the body has changed significantly over time-from a simple physical barrier to a complex system encompassing local and systemic regulation of numerous processes in the body. Endothelium disorders may arise from impairment of one or more signaling pathways affecting dilator or constrictor activity, including nitric oxide-cyclic guanosine monophosphate activation, prostacyclin-cyclic adenosine monophosphate activation, phosphodiesterase inhibition, and potassium channel activation or intracellular calcium level inhibition. In this review, plants are summarized as sources of biologically active substances affecting the endothelium. This paper compares individual substances and mechanisms that are known to affect the endothelium, and which subsequently may cause the development of cardiovascular disorders.
- Klíčová slova
- endothelium, nitric oxide, vasoactive substances, vasoconstriction, vasodilation,
- MeSH
- cévní endotel cytologie účinky léků fyziologie MeSH
- lidé MeSH
- rostlinné extrakty chemie farmakologie MeSH
- rostliny chemie metabolismus MeSH
- sekundární metabolismus * MeSH
- vazodilatace účinky léků fyziologie MeSH
- vazodilatancia chemie farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- rostlinné extrakty MeSH
- vazodilatancia MeSH
BACKGROUND: Inflammatory-mediated pathological processes in the endothelium arise as a consequence of the dysregulation of vascular homeostasis. Of particular importance are mediators produced by stimulated monocytes/macrophages inducing activation of endothelial cells (ECs). This is manifested by excessive soluble pro-inflammatory mediator production and cell surface adhesion molecule expression. Nitro-fatty acids are endogenous products of metabolic and inflammatory reactions that display immuno-regulatory potential and may represent a novel therapeutic strategy to treat inflammatory diseases. The purpose of our study was to characterize the effects of nitro-oleic acid (OA-NO2) on inflammatory responses and the endothelial-mesenchymal transition (EndMT) in ECs that is a consequence of the altered healing phase of the immune response. METHODS: The effect of OA-NO2 on inflammatory responses and EndMT was determined in murine macrophages and murine and human ECs using Western blotting, ELISA, immunostaining, and functional assays. RESULTS: OA-NO2 limited the activation of macrophages and ECs by reducing pro-inflammatory cytokine production and adhesion molecule expression through its modulation of STAT, MAPK and NF-κB-regulated signaling. OA-NO2 also decreased transforming growth factor-β-stimulated EndMT and pro-fibrotic phenotype of ECs. These effects are related to the downregulation of Smad2/3. CONCLUSIONS: The study shows the pleiotropic effect of OA-NO2 on regulating EC-macrophage interactions during the immune response and suggests a role for OA-NO2 in the regulation of vascular endothelial immune and fibrotic responses arising during chronic inflammation. GENERAL SIGNIFICANCE: These findings propose the OA-NO2 may be useful as a novel therapeutic agent for treatment of cardiovascular disorders associated with dysregulation of the endothelial immune response.
- Klíčová slova
- Endothelial cells, Endothelial-mesenchymal transition, Macrophages, Nitro-fatty acids, Nitro-oleic acid, Vascular inflammation,
- MeSH
- cévní endotel cytologie účinky léků metabolismus MeSH
- endoteliální buňky účinky léků metabolismus MeSH
- epitelo-mezenchymální tranzice * MeSH
- kyseliny olejové farmakologie MeSH
- lidé MeSH
- makrofágy účinky léků metabolismus MeSH
- MAP kinasový signální systém MeSH
- myši MeSH
- NF-kappa B metabolismus MeSH
- proteiny Smad metabolismus MeSH
- transformující růstový faktor beta farmakologie MeSH
- transkripční faktory STAT metabolismus MeSH
- zánět metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- 10-nitro-oleic acid MeSH Prohlížeč
- kyseliny olejové MeSH
- NF-kappa B MeSH
- proteiny Smad MeSH
- transformující růstový faktor beta MeSH
- transkripční faktory STAT MeSH