Mechanisms for forming endothelium dysfunction in insulin-resistant conditions

2020 ◽  
pp. 32-36
Author(s):  
S. S. Bayramova ◽  
O. V. Tsygankova ◽  
K. Yu. Nikolayev ◽  
A. A. Starichkova
Keyword(s):  
Endothelial Dysfunction ◽  
Vascular Wall ◽  
Vascular Pathology ◽  
Inflammatory Factors ◽  
Modern Concept ◽  
Endothelial Lining ◽  
Endothelium Dysfunction ◽  
Insulin Resistant ◽  
And Function

In pathogenesis and clinic of arterial hypertension, atherosclerosis, diabetes mellitus and their complications, one of the important aspects is the violation of the structure and function of the endothelium. In these diseases, it appears as the primary organ of the target, as the endothelial lining of the vessels participates in the regulation of vascular tone, hemostasis, immune response, migration of blood cells to the vascular wall, the synthesis of inflammatory factors and their inhibitors, and performs barrier functions. Endothelial dysfunction (ED) is characterized by a shift in the endothelium towards decreasing vasodilation, proinflammatory state and prothrombotic properties. Currently, ED is considered as a universal mechanism for the formation and progression of any vascular pathology, especially in patients with type 2 diabetes. In routine clinical practice, the detection of ED is not carried out, but it must be understood that endothelial dysfunction is one of the first manifestations of vascular pathology, which appears long before the clinical manifestation of cardiovascular diseases. The review provides data on the functions and dysfunctions of the vascular endothelium, and also presents the modern concept of ED as the central link in many chronic diseases.

scholarly journals Pre-eclampsia in a mother and programming of the child’s cardiovascular health

2019 ◽  
Vol 64 (4) ◽  
pp. 19-25 ◽  
Author(s):  
O. P. Kovtun ◽  
P. B. Tsyvian
Keyword(s):  
Cardiovascular System ◽  
Cardiovascular Health ◽  
Experimental Studies ◽  
Experimental Models ◽  
System Structure ◽  
Inflammatory Factors ◽  
Modern Concept ◽  
Endothelium Dysfunction ◽  
Phenotype Formation ◽  
And Function

The authors present a review of the literature devoted to the problem of programming the formation of the cardiovascular system structure and function in children born from mothers with preeclampsia. These children are at high risk of developing cardiovascular diseases. Pre-eclampsia is caused by the endothelium dysfunction, deregulation of the immune and inflammatory factors during pregnancy. Experimental studies identify these factors as key epigenetic factors programming the condition of the cardiovascular system of the offspring. The modern concept of intrauterine programming, describing this phenomenon, focuses on three main areas of research: experimental models simulating the intrauterine environment with preeclampsia; research of the pathological phenotype formation under the influence of these factors; epigenetic studies of the influence of preeclampsia on the cardiovascular system functioning. The article discusses the perspectives of epigenetic programming prevention.

scholarly journals Mitochondrial dysfunction and insulin resistance from the outside in: extracellular matrix, the cytoskeleton, and mitochondria

2011 ◽  
Vol 301 (5) ◽  
pp. E749-E755 ◽  
Author(s):  
Dawn K. Coletta ◽  
Lawrence J. Mandarino
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Extracellular Matrix ◽  
Contractile Activity ◽  
Cytoskeletal Proteins ◽  
Altered Expression ◽  
Insulin Resistant ◽  
And Function

Insulin resistance in skeletal muscle is a prominent feature of obesity and type 2 diabetes. The association between mitochondrial changes and insulin resistance is well known. More recently, there is growing evidence of a relationship between inflammation, extracellular remodeling, and insulin resistance. The intent of this review is to propose a potentially novel mechanism for the development of insulin resistance, focusing on the underappreciated connections among inflammation, extracellular remodeling, cytoskeletal interactions, mitochondrial function, and insulin resistance in human skeletal muscle. Several sources of inflammation, including expansion of adipose tissue resulting in increased lipolysis and alterations in pro- and anti-inflammatory cytokines, contribute to the insulin resistance observed in obesity and type 2 diabetes. In the experimental model of lipid oversupply, an inflammatory response in skeletal muscle leads to altered expression extracellular matrix-related genes as well as nuclear encoded mitochondrial genes. A similar pattern also is observed in “naturally” occurring insulin resistance in muscle of obese nondiabetic individuals and patients with type 2 diabetes mellitus. More recently, alterations in proteins (including α-actinin-2, desmin, proteasomes, and chaperones) involved in muscle structure and function have been observed in insulin-resistant muscle. Some of these cytoskeletal proteins are mechanosignal transducers that allow muscle fibers to sense contractile activity and respond appropriately. The ensuing alterations in expression of genes coding for mitochondrial proteins and cytoskeletal proteins may contribute to the mitochondrial changes observed in insulin-resistant muscle. These changes in turn may lead to a reduction in fat oxidation and an increase in intramyocellular lipid, which contributes to the defects in insulin signaling in insulin resistance.

scholarly journals CONNECTION OF THE ENDOTHELIAL DYSFUNCTION FACTORS AND DIABETES MELLITUS 2 TYPE SEVERITIES

2018 ◽  
Vol 14 (1-2) ◽  
pp. 34-39
Author(s):  
S.V. Ziablytsev ◽  
T.I. Panova ◽  
O.P. Chernobryvtsev
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Endothelial Dysfunction ◽  
Inflammatory Factors ◽  
Control Group ◽  
Blood Levels ◽  
Diene Conjugates ◽  
Hospital Patients ◽  
Severe Degree

Relevance. In the case of diabetes mellitus (DM), a whole cascade of pathological reactions unfolds in the endothelium of the vessels that afflict glucose toxicity, excessive action of stimulating hypertension and inflammatory factors, thrombotic activators, and the intensification of oxidative stress, which leads to the formation of endothelial dysfunction (EDF). On the other hand, the damaged endothelium itself is included in the pathogenesis of diabetes and causes the development of further violations. Objective: to investigate the association of EDF factors: endothelin 1 (ET1), endothelial NO-synthase (eNOS), nitric oxide (NO), tumor necrosis factor (TNFα), and diene conjugates (DC) with severity of type 2 diabetes. Materials and methods. Data were used for 152 hospital patients with type 2 diabetes at the age from 34 to 80 years (53.9±8.4 years). Women were 95 (62.5%), men – 57 (37.5%). According to the degree of severity of patients was divided into three groups: 1st (37.5% of patients) – the average stage in the compensation stage (HbA1s 7-9%), 2nd (41.4%) – the average stage in the stage of decompensation (HbA1s more than 9%), 3rd (21,1%) – a severe degree in the stage of decompensation. The control group included 95 practically healthy individuals. The plasma levels of the blood were determined by the enzyme-linked method: ЕТ1 (Biomedica Immunoassays, Austria), eNOS (BCM Diagnostics, USA) і TNFα (Bender Medsystems, Austria). The level of blood NO and DC were determined biochemically (spectrophotometer Specord, Germany). Statistica 10 (StatSoft, Inc., USA) was used to statistically process the data obtained. Results. Levels of EDF factors depended on the severity of DM 2 type. Thus, the level of ETI in patients exceeded control in 3.7-4.7 times (p<0.001) with the maximum values in the 2nd and 3rd groups; also increased blood levels of NO (1.4-1.5 times; p<0.001). The highest increase was observed in TNFα levels (4.2-6.5 times; p<0.001) and DC (2.3-2.7 times; p<0.001). The blood content of eNOS in the patients' groups was lower when compared with control (1.3-1.9 times; p<0.001). Single-factor regression analysis showed that ET1 caused high glycemia, albuminuria, increased the degree of decompensation of DM 2 type and the degree of diabetic nephropathy. NO accumulation in the blood affects the decrease in glomerular filtration rate and the deterioration of renal function. TNFα and DC contributed to almost all key indicators of DM 2 type, which had a synergistic effect with other EDF factors. Conclusion. Factors of EDF are closely linked with clinical and laboratory indicators of severity of DM 2 type, which highlights them in the pathogenesis of the disease.

scholarly journals ENDOTHELIAL DYSFUNCTION IN TYPE 2 DIABETES. Review

2019 ◽  
Vol 15 (1-2) ◽  
pp. 80-86
Author(s):  
O.P. Chernobrivtsev ◽  
S.V. Zyablitsev ◽  
T.I. Panova ◽  
Yu.O. Panchenko
Keyword(s):  
Nitric Oxide ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Microvascular Complications ◽  
Vascular Complications ◽  
No Synthase ◽  
Modern Concept

Relevance. The problem of systematization and refinement of modern concepts of the pathogenesis of endothelial dysfunction (EDF) and its role in the development of microvascular complications of type 2 diabetes mellitus (T2DM) is relevant due to the lack of pathogenetic treatment nowadays, which would include endothelial dysfunction. Objective: to conduct an analytical review of the results of scientific research on the mechanisms of EDF in T2DM, with the aim of proposing an integrated modern concept of the pathogenesis of EDF. Materials and methods. Review of scientific publications in the international electronic scientific databases of PubMed, Embase and Scopus for keywords for the entire available period (1982-2019). Results. The article provides modern data on the modern concept of the pathogenesis of EDF and its role in the development of microvascular complications in T2DM. The pathogenesis of EDF in type 2 diabetes mellitus is based on the following key mechanisms: impaired synthesis of the endothelial fraction of nitric oxide (NO) due to inhibition of the activity of endothelial NO synthase (eNOS); decreased bioavailability of NO because of oxidative stress; activation of the formation of Endothelin-1 (ET1) and expression of endothelin receptors with a predominance of vasoconstriction; inflammation, which is supported by the synthesis of pro-inflammatory cytokines and causes the expression of inducible NO synthase (iNOS), which stimulates the synthesis of a significant amount of NO, which enters into free radical reactions with the formation of cytotoxic products. Conclusions. The pathogenesis of endothelial dysfunction is impaired nitric oxide synthesis. Endothelial dysfunction, as an integral mechanism, underlies in the core mechanisms the development of vascular complications in type 2 diabetes.

scholarly journals The endothelial glycocalyx: research methods and prospects for their use in endothelial dysfunction assessment

2020 ◽  
Vol 19 (1) ◽  
pp. 5-16
Author(s):  
T. D. Vlasov ◽  
O. A. Lazovskaya ◽  
D. A. Shimanski ◽  
I. I. Nesterovich ◽  
N. L. Shaporova
Keyword(s):  
Endothelial Dysfunction ◽  
Vascular System ◽  
Three Dimensional ◽  
Dark Field ◽  
Endothelial Glycocalyx ◽  
Prognostic Indicators ◽  
Modern Concept ◽  
Non Invasive ◽  
Dimensional Network ◽  
And Function

A modern concept of the endothelial dysfunction in the pathogenesis of many diseases includes the glycocalyx damage along with impaired of the morphology and function of endothelial cells. The glycocalyx is a gel-like submembrane complex of protein-carbohydrate, carbohydrate-lipid components and plasma molecules forming a three-dimensional network on the luminal surface of the endothelium. The features of the borderline location of endothelial glycocalyx in the vascular system determine various important functions: barrier, regulatory, anti-inflammatory, antithrombotic, mechanotransduction ones, etc. In recent years, due to the improvement of visualization methods endothelial glycocalyx structure has been detailed. Its physiological functions and the role in the development of some pathological conditions have been clarified. Modern methods of glycocalyx assessment include invasive and non-invasive research techniques. The most promising ones are dark-field microscopy and the determination of glycocalyx-associated biochemical markers. Endothelial glycocalyx damage is a universal pathogenetic component and the earliest marker of the development of most diseases. Therefore, the endothelial glycocalyx assessment refers to promising areas of research. The ability to correlate with other prognostic indicators allows us to consider the endothelial glycocalyx damage as a marker of the poor health prognosis. That is why, assessment of the endothelial glycocalyx condition will allow to personalize treatment and to prevent the diseases progression.

scholarly journals CONNECTION OF THE ENDOTHELIAL DYSFUNCTION FACTORS AND DIABETES MELLITUS 2 TYPE SEVERITIES

2018 ◽  
Vol 14 (1-2) ◽  
pp. 34-39
Author(s):  
S.V. Ziablytsev ◽  
T.I. Panova ◽  
O.P. Chernobryvtsev
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Endothelial Dysfunction ◽  
Inflammatory Factors ◽  
Control Group ◽  
Blood Levels ◽  
Diene Conjugates ◽  
Hospital Patients ◽  
Severe Degree

Relevance. In the case of diabetes mellitus (DM), a whole cascade of pathological reactions unfolds in the endothelium of the vessels that afflict glucose toxicity, excessive action of stimulating hypertension and inflammatory factors, thrombotic activators, and the intensification of oxidative stress, which leads to the formation of endothelial dysfunction (EDF). On the other hand, the damaged endothelium itself is included in the pathogenesis of diabetes and causes the development of further violations. Objective: to investigate the association of EDF factors: endothelin 1 (ET1), endothelial NO-synthase (eNOS), nitric oxide (NO), tumor necrosis factor (TNFα), and diene conjugates (DC) with severity of type 2 diabetes. Materials and methods. Data were used for 152 hospital patients with type 2 diabetes at the age from 34 to 80 years (53.9±8.4 years). Women were 95 (62.5%), men – 57 (37.5%). According to the degree of severity of patients was divided into three groups: 1st (37.5% of patients) – the average stage in the compensation stage (HbA1s 7-9%), 2nd (41.4%) – the average stage in the stage of decompensation (HbA1s more than 9%), 3rd (21,1%) – a severe degree in the stage of decompensation. The control group included 95 practically healthy individuals. The plasma levels of the blood were determined by the enzyme-linked method: ЕТ1 (Biomedica Immunoassays, Austria), eNOS (BCM Diagnostics, USA) і TNFα (Bender Medsystems, Austria). The level of blood NO and DC were determined biochemically (spectrophotometer Specord, Germany). Statistica 10 (StatSoft, Inc., USA) was used to statistically process the data obtained. Results. Levels of EDF factors depended on the severity of DM 2 type. Thus, the level of ETI in patients exceeded control in 3.7-4.7 times (p<0.001) with the maximum values in the 2nd and 3rd groups; also increased blood levels of NO (1.4-1.5 times; p<0.001). The highest increase was observed in TNFα levels (4.2-6.5 times; p<0.001) and DC (2.3-2.7 times; p<0.001). The blood content of eNOS in the patients' groups was lower when compared with control (1.3-1.9 times; p<0.001). Single-factor regression analysis showed that ET1 caused high glycemia, albuminuria, increased the degree of decompensation of DM 2 type and the degree of diabetic nephropathy. NO accumulation in the blood affects the decrease in glomerular filtration rate and the deterioration of renal function. TNFα and DC contributed to almost all key indicators of DM 2 type, which had a synergistic effect with other EDF factors. Conclusion. Factors of EDF are closely linked with clinical and laboratory indicators of severity of DM 2 type, which highlights them in the pathogenesis of the disease.

Von Willebrand disease and Weibel-Palade bodies

2010 ◽  
Vol 30 (03) ◽  
pp. 150-155 ◽  
Author(s):  
J. W. Wang ◽  
J. Eikenboom
Keyword(s):  
Platelet Adhesion ◽  
Coagulation Factor ◽  
Von Willebrand Disease ◽  
Inflammatory Factors ◽  
Limited Data ◽  
Storage Organelle ◽  
And Function ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryVon Willebrand factor (VWF) is a pivotal haemostatic protein mediating platelet adhesion to injured endothelium and carrying coagulation factor VIII (FVIII) in the circulation to protect it from premature clearance. Apart from the roles in haemostasis, VWF drives the formation of the endothelial cell specific Weibel-Palade bodies (WPBs), which serve as a regulated storage of VWF and other thrombotic and inflammatory factors. Defects in VWF could lead to the bleeding disorder von Willebrand disease (VWD).Extensive studies have shown that several mutations identified in VWD patients cause an intracellular retention of VWF. However, the effects of such mutations on the formation and function of its storage organelle are largely unknown. This review gives an overview on the role of VWF in WPB biogenesis and summarizes the limited data on the WPBs formed by VWD-causing mutant VWF.

A Computerized Coding System for Processing Basic Histopathological Changes – Application to Vascular Pathology

1986 ◽  
Vol 25 (03) ◽  
pp. 139-142 ◽  
Author(s):  
A. Mauriello ◽  
Y. Sambuy ◽  
E. Bonanno ◽  
A. Orlandi ◽  
G. Palmieri ◽  
...  
Keyword(s):  
Vascular Wall ◽  
Final Diagnosis ◽  
Vascular Pathology ◽  
Histopathological Study ◽  
Coding System ◽  
Histopathological Changes ◽  
Histological Changes ◽  
Pathological Conditions ◽  
Computer Based ◽  
Sufficient Space

SummaryAmong the numerous existing computer-based systems for processing pathological data, none contains sufficient space for encoding data on the basic cytological or histological changes of a certain organ or tissue, upon which the final diagnosis is based.An “analytical record” was constructed listing all the basic changes that can be encountered in the various pathological conditions of the vascular wall. The data collected on the “analytical record” were coded by means of an alphanumeric code and stored in an Apple II 48 K minicomputer.The advantages of this system include the computerization of the data by non-specialized personnel and the possibility to’ quantitatively analyze the histocytopathological parameters used for diagnosis in vascular pathology. This coding system may easily be adapted, with minor modifications, to the histopathological study of other organs and tissues.

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