Biochemical Markers Of Endothelial Dysfunction Research Articles

Diagnosis and management of hypertension understanding imperative role of various biomarkers

As hypertension, almost 90% of cases of hypertension with an unknown origin called essential hypertension, continue to be one of the most important risk factors for various fatal health conditions, its early diagnosis using trustworthy biomarkers to predict, diagnose, and monitor the therapeutic progress of hypertension is proving to be of utmost importance for the preventive as well as curative purpose of various health hazards. A rise in the activity of biochemical markers of endothelial dysfunction and blood lipids, notablyLow-density lipoprotein (LDL) andverylow-density lipoprotein(VLDL)measurements, and inflammation markers including C-reactive protein(CRP), cytokines, and adhesion molecules are linked to the development of hypertension. Growth and differentiation factor-15, red cell distribution width, uric acid, creatinine, inflammatory markers including interleukin-6, angiopoietins, and microRNAs are prognostic indicators in individuals with pulmonary arterial hypertension (PAH).The most extensively used blood markers for portal hypertension (PH) are the fibrosis-4 index and the improved liver fibrosis test. Likewise, Hepatic venous pressure gradient (HVPG), liver/SSMs and Plasma cyclic guanosine monophosphate (cGMP) being clinically significant tools to assess for PH. Along with Copeptin, serum levels of uric acid, potassium, and sodium may be crucial for the identification and monitoring of hypertension in pediatrics.Similarly, the severity of gestational hypertension correlates with hyperuricemia, elevated CRP, and interleukin-1 serum levels. Here, in this study, literature on biomarkers has been reviewed which are versatile diagnostic tools posing that influence healthcare professionals’ judgment and assist in patient education regarding diagnosis, prognosis, early detection, and treatment intervention.

The role of intestinal dysbiosis in endothelial dysfunction evolution in patients with microvascular angina

Purpose. Evaluation of circulating levels of lipopolysaccharide and zonulin in conjunction with markers of endothelial dysfunction, inflammation, and oxidative stress in patients with microvascular angina (MА). Material and methods. The study was carried out in a group of 58 patients with MA hospitalized in the Institute of Cardiology. The determination of circulating levels of 20 biomarkers was carried out in cooperation with the laboratory investigation center of Sapienza University (Italy). All functional and biochemical markers were also determined in 48 apparently healthy people (control group) with the values of which the markers of MA patients were compared. Results. Endothelial dysfunction in patients with MA excelled by increasing the thickness of the intima-media complex of the carotid artery by 41%, as well as by reducing of flow-mediated brachial artery dilatation (FMD) by 31,6%. The presence of dysbiosis was manifested by an 80% increase in the serum content of lipopolysaccharides (LPS) and by doubling of zonulin (1,8±0,3 vs 3,6±0,7 ng/ml). Endothelial dysfunction and dysbiosis evolved in association with oxidative stress activation estimated by means of 6 markers and increased serum content of 6 important pro-inflammatory markers (hsCRP, IL-6, TNF-α, etc.) Conclusions. 1. In patients with MA, elevated circulating levels of LPS and zonulin more than twice compared to the control value were found, which indicates the presence of intestinal dysbiosis. 2. LPS and zonulin correlate robustly with morphofunctional and biochemical markers of endothelial dysfunction, as well as with markers of its main pathogenetic factors, - inflammation and oxidative stress.

Прогнозування і профілактика прееклампсії при багатоплідній вагітності після допоміжних репродуктивних технологій

Purpose - to assess the effectiveness of the implemented algorithm of treatment and preventive measures by analyzing the course of pregnancy, childbirth and the condition of newborns in multiple pregnancies after assisted reproductive technologies to assess of changes in biochemical markers of endothelial dysfunction in the detection of pre-clinical manifestations of preeclampsia in pregnant women with multiple pregnancies after the use of assisted reproductive technologies. Materials and methods. A prospective study of pregnant women with dichorionic diamniotic twins after assisted reproductive technologies was conducted: the Group І (main) - 35 pregnant women with twins who were offered a developed monitoring algorithm; the Group ІІ (control) 27 pregnant women who were monitored according to generally accepted methods of managing multiple pregnancies. Statistical processing of the research results was carried out using standard programs “Microsoft Excel 5.0” and “Statistica 6.0”. Results. In the Group І 2 cases of moderate preeclampsia were found in 32 and 33 weeks of pregnancy (PLGF results - 63.2 pg/ml and 58.7 pg/ml, sFlt-1/PLGF ratio - 51.7 and 66.3). In the Group II 4 cases of preeclampsia were identified: 2 cases of moderate preeclampsia (PLGF - 74.1 pg/ml and 69.3 pg/ml, sFlt-1/PLGF ratio - 98.6 and 104.5); 2 cases of severe preeclampsia at 33 and 34 weeks (PLGF data - 44.1 pg/ml and 47.3 pg/ml, sFlt-1/ PLGF ratio 122.4 and 130.1) against the background of signs of gestational hypertension. Fetal growth retardation in the Group І was noted in 3 (8.6%) women (І stage - in 2 (5.7%) cases, II stage - in 1 (2.9%) case, III stage was not diagnosed), in the Group II - in 7 (25.9%) women (I stage - in 2 (7.4%) cases, II stage - in 4 (14.8%) cases, III stage - in 1 (3.7%) case). Fetal distress in the Group І was detected in 4 (11.4%) pregnant women (during pregnancy - in 1 (2.9%) case, during deliveries - in 3 (8.6%) cases); in the Group II - in 7 (25.9%) women (during pregnancy - in 5 (18.5%) cases, during deliveries - in 2 (7.4%) cases). Premature deliveries in the Group I was noted in 5 (14.3%) women (before 34 weeks of gestation - in 2 (5.7%) cases, after 34 weeks of gestation - in 3 (8.6%) cases); in the Group II - in 8 (29.6%) women (before 34 weeks of gestation - in 5 (18.5%) cases, after 34 weeks of gestation - in 3 (11.1%) cases). Premature detachment of a normally located placenta was detected in 2 (7.4%) women in the Group II, and in the Group I such cases were not recorded. Vaginal delivery was observed in 14 (40%) women in the Group I and 7 (25.9%) patients in the Group II; cesarean section - in 21 (60%) and 19 (70.4%) women, respectively. Combined delivery was performed in 1 (3.7%) woman of the Group II, and in the Group I - not recorded. Hypoxic-ischemic lesions were detected in 2 (5.7%) children from women of the Group I and in 4 (14.8%) children from mothers of the Group II. Adaptation disorders were noted in 5 (14.3%) cases in the Group I and in 8 (29.6%) cases in the Group II. Transfer to the second stage of treatment required 3 (8.6%) children from mothers of the Group I and 6 (22.2%) children from mothers of the Group II. Conclusions. The proposed algorithm of modern diagnostic and treatment-prophylactic measures made it possible to reliably reduce the frequency of development of preeclampsia, obstetric and perinatal complications and can be recommended for use in practical health care. The study of the anti-angiogenic factor sFlt-1 and the pro-angiogenic factor PLGF and their ratio is promising in the prediction and early diagnosis of preeclampsia in multiple pregnancies after assisted reproductive technologies. The use of Triage PLGF and sFlt-1/PLGF ratio should be widely implemented in the practice of obstetrician-gynecologists as a prognostic marker for early recognition of preeclampsia in order to reduce perinatal complications, both from the mother and the fetus. Based on monitoring the growth dynamics of the sFlt-1/PLGF ratio, it is possible to predict the early development of preeclampsia even without clinical symptoms, and to make a decision about the possibility of extending the pregnancy or the need for urgent delivery. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the author.

Маркери ангіоґенезу та їх роль у прогнозуванні прееклампсії при багатоплідній вагітності

Purpose - to identify changes in biochemical markers of endothelial dysfunction, preclinical manifestations of preeclampsia in pregnant women with multiple pregnancies after the use of assisted reproductive technologies. Materials and methods. A prospective study of pregnant women with dichorionic diamniotic twins after assisted reproductive technologies was conducted: 35 pregnant women with twins who were offered a developed monitoring algorithm (main (І) group) and 27 pregnant women who were monitored according to generally accepted methods of managing multiple pregnancies (control (ІІ) group). Statistical processing of the research results was carried out using standard programs “Microsoft Excel 5.0” and “Statistica 6.0”. Results. During the analysis of the main and control observation groups, an increase in the pro-angiogenic biomarker PlGF was noted up to 28 weeks (I group 604.9 (83.4-814.5) pg/ml vs. 568.6 (68.1-765.3) pg/ml in the II group). Іn the term of 26-28 weeks, in the main group, we noted a decrease in the level of PlGF below 100 pg/ml in 4 (11.4%) women, and in the II group in 6 (22.2%), however, clinical manifestations of preeclampsia, in patients, it was not noted. In the period of 32-34 weeks, the results of PlGF below the level of 100 pg/ml were obtained in 6 (17.1%) women of the I group against 7 (25.9%) of the women of the II group. In the group I we found 2 cases of moderate preeclampsia at 32 and 33 weeks of pregnancy. In the II group 4 cases of preeclampsia were identified. Two cases of moderate preeclampsia, which clinically manifested at 30 weeks. Conclusions. The anti-angiogenic factor, sFlt-1 and the pro-angiogenic factor PIGF, and their relationship are promising markers in the prediction and early diagnosis of preeclampsia in the multiple pregnancies after assisted reproductive technologies. Based on monitoring the growth dynamics of the sFlt-1/PIGF ratio, it is possible to predict the early development of preeclampsia even without clinical symptoms, and to make a decision about the possibility of extending the pregnancy or the need for urgent delivery. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

ЕНДОТЕЛІАЛЬНА ДИСФУНКЦІЯ В УМОВАХ ЕКСПЕРИМЕНТАЛЬНОГО СУБАРАХНОЇДАЛЬНОГО КРОВОВИЛИВУ. МОЖЛИВІ ШЛЯХИ ФАРМАКОКОРЕКЦІЇ

Purpose of the article: to study the effect of acelysine and nimodipine on certain endothelial dysfunction indicators and to evaluate their therapeutic efficacy after subarachnoid hemorrhage in rats. Materials and Methods: an experimental study was carried out using 50 Wistar rats of both sexes. Spontaneous subarachnoid hemorrhage was modeled in animals. Three groups of animals were identified: a control group, a group of animals received a standard therapeutic dose of acelysine, and a group received a standard therapeutic dose of nimotop. Each group included 15 animals. There were also 5 intact animals. The animals were withdrawn from the experiment on days 4 and 7 after the motor and exploratory activity determination. Motor and exploratory activity determination was carried out following SAH with the “Open Field” technique. Determination of biochemical markers of endothelial dysfunction was performed in a rat brain homogenate. Results and discussion. It was found that modeling of subarachnoid hemorrhage (SAH) led to the oxidative stress development development and the product of oxidative modification of proteins (nitrotyrosine (Ntz) on the 4th and especially on the 7th day of the experiment) increase in the brain tissues. Starting from the 4th day, we registered a compensatory increase in the activity of NO-synthase (NOS) - by 56%, followed by a decrease in its activity on the 7th day, by more than 33% against the intact group of animals. It was registered a compensatory increase in VEGF-A in rats with SAH modeling on the 4th day of the experiment and its further decrease on the 7th day. The established pathobiochemical changes in the brain tissue were accompanied by the cognitive deficit development in experimental animals, especially on the 7th day of the SAH. SAH led to a significant decrease in the total activity of animals by 2.63 times, a decrease in the distance traveled by animals by 1.89 times, the number of freezes increased by 1.86 times and the immobility of animals increased when moving from the periphery to the center and immobility in the center of the arena (anxiety, fear, disorientation), as well as a decrease in the distance traveled and the speed of movement in illuminated center of the arena 2 and 2.6 times, respectively. Experimental therapy with acelysine 15 mg/kg led to the normalization of biochemical indicators of endothelial dysfunction: concentration of nitrotyrosine, starting from the 4th day of the experiment, increased eNOS activity and VEGF-A concentration (by 75% and 64% on 7th day). The administration of namidopine led to less pronounced effects, statistically significant changes occurred only in relation to the VEGF-A concentration. Administration of namidopine resulted in only a slight increase in VEGF-A concentration. Acelysine and nimotope significantly increased the total activity of rats on the 7th day after SAH by 76.3% and 48.8%, respectively. In animals treated with acelysine, anxiety and fear decreased. The animals were less aggressive and more empathic - long-term grooming increased 3 times. The administration of nimotop in rats survived SAH had a less pronounced positive effect on behavior. Nimotop did not effect on indicators of general activity and did not increase the total distance traveled. Animals received nimtop were inactive by the 7th day of treatment. Conclusions: Experimental therapy with acelysine led to the normalization of biochemical parameters of endothelial dysfunction, namely nitrotyrosine concentration, starting from the 4th day of the experiment and increased eNOS activity and VEGF-A concentration. It should be noted that, in contrast to the rats of the control group, under prescription of acelysine, there was an increase in the concentration of eNOS and VEGF-A both on the 4th and 7th days of the experiment. The administration of namidopine led to less pronounced effects, statistically significant changes occurred only in relation to the VEGF-A concentration. The administration of acelysin to animals after SAH had a beneficial effect on the emotional status and behavior of animals, and also led to the normalization of their general activity and orientation-exploratory activity. The mechanism of edotheliotropic effect of acelysine, in our opinion, is associated with its antioxidant effects, modulating impact on endothelial NOS, as well as its property, indirectly, to influence on increase VEGF content. Nimotope therapy had no effect on the emotional status and behavior of the animals. The use of calcium channel blockers revealed such side effects as depression, drowsiness, diplopia, and disorientation

The impact of perindopril and metformin on the markers of endothelial dysfunction in rats with acute intracerebral hemorrhage and type 2 diabetes mellitus

This comparative research is aimed to study the effect of perindopril and metformin on the levels of biochemical markers of endothelial dysfunction in rats with type 2 diabetes mellitus (T2DM) complicated by a brain hemorrhage. The study was carried out on 30 white male Wistar rats. T2DM was simulated by a single intraperitoneal injection of nicotinamide and streptozotocin (NA/STZ). Intracerebral hemorrhage (ICH) was induced by microinjection of 1 μL of bacterial collagenase 0.2 IU/μL into the striatum on the 60th day of the experiment. Animals were randomized into 5 groups: A – negative control (intact, n=6); B – positive control 1 (NA/STZ, n=6); C – positive control 2 (NA/STZ+ICH, n=6); D – perindopril (“Prestarium”, 2 mg/kg+NA/STZ+ICH, n=6); E – metformin (“Siofor”, 250 mg/kg+NA/STZ+ICH, n=6). The studied drugs were administered intragastrically for 20 days, starting from the 50th day after the induction of T2DM. Endothelial function was assessed by the content of homocysteine (Hcy), advanced glycation end products (AGEs), endothelin-1 (ET-1), and von Willebrand factor (vWF) in blood serum. It was found that long-term separate T2DM is accompanied by hyperhomocysteinemia, as well as an increase in AGEs, ET-1, and vWF levels, indicating dysregulation of the hemostasis system and vascular tone. It should be noted that brain hemorrhage in T2DM can enhance these manifestations, although the obtained differences were characterized only by a persistent trend. At the same time, the effect of perindopril was limited only by a significant decrease in AGEs levels by 31.2% (p<0.05). In turn, the action of metformin was characterized by a positive glycemic control, as well as an effect on the state of the vascular endothelium, namely, a significant decrease in AGEs, ET-1 and vWF levels by 37.6% (p<0.05); 5.5% (p<0.05) and 9.5% (p<0.05), respectively. It was also found that the endotheliotropic properties of the studied drugs were not associated with an effect on homocysteine levels. Thus, metformin in conditions of diabetes mellitus complicated by acute intracerebral hemorrhage has advantages over perindopril in relation to endothelial dysfunction.

P7‐15: Biochemical markers of endothelial dysfunction in patients with chronic obstructive diseases of the lungs of different categories of risk of exacerbations

P7‐15: Biochemical markers of endothelial dysfunction in patients with chronic obstructive diseases of the lungs of different categories of risk of exacerbations

Ультразвукові та біохімічні показники дисфункції ендотелію при геморагічному васкуліті у дітей

З метою виявлення ультразвукових і біохімічних маркерів дисфункції ендотелію залежно від ступеня активності та форми обстежено 60 дітей з геморагічним васкулітом. Проводили визначення в сироватці крові концентрації МСР-1 імуноферментним методом, вмісту оксиду азоту — за концентрацією його стабільних метаболітів — NO2, NO3 та S-нітрозотіолу, фактора Віллебранда — агрегометричним методом, оцінку товщини комплексу інтима-медіа загальної сонної артерії та визначення ендотелійзалежної дилатації плечової артерії. Рівні фактора Віллебранда та МСР-1 вірогідно підвищуються залежно від ступеня активності геморагічного васкуліту. Статистичні дані вказують на значне зниження концентрації метаболітів оксиду азоту в сироватці крові у дітей зі змішаною формою та нирковим синдромом. Товщина комплексу інтима-медіа загальної сонної артерії збільшувалась у дітей із тяжким перебігом геморагічного васкуліту та у дітей зі змішаною формою з нирковим синдромом. Зафіксована патологічна реакція ендотелійзалежної дилатації плечевої артерії незалежно від ступеня активності та форми геморагічного васкуліту свідчить про безпосереднє залучення в патологічний процес ендотелію.

Endothelin-1 and LOX-1 as Markers of Endothelial Dysfunction in Obstructive Sleep Apnea Patients.

Introduction: The search of biochemical markers of endothelial dysfunction: lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1)—involved in atherosclerotic plaques formation—and endothelin-1 (ET-1)—potent vasoconstrictor-might help in detecting obstructive sleep apnea (OSA) patients at high risk of cardiovascular diseases. Material and Methods: In 71 OSA patients (apnoea/hypopnoea index, AHI 28.2 ± 17.9/hour) and in 21 healthy controls the serum levels of LOX-1 and ET-1 were measured. Results: There were increased levels of ET-1 (1.58 ± 0.65 vs. 1.09 ± 0.38 pg/mL; p < 0.001) but not of LOX-1 in OSA patients as compared with healthy controls. In the patients’ group ET-1 levels negatively correlated with serum LDL levels. LOX-1 levels positively correlated with fasting glucose levels and were higher in the patients with than without diabetes. Neither ET-1 nor LOX-1 correlated with OSA severity. In mild OSA patients, there was a negative correlation between LOX-1 and mean arterial oxygen saturation during sleep. In severe OSA patients, there was a positive correlation between LOX-1 levels and uric acid. Conclusion: There is endothelial dysfunction in OSA patients as indicated by increased serum levels of ET-1 and possibly endothelial dysfunction in diabetic OSA patients as indicated by increased serum levels of LOX-1 and its correlation with fasting glucose levels.

Analysis of relationships between biochemical markers of endothelial dysfunction in chronic mercury exposure

Introduction. The cause of the development of endothelial dysfunction (ED) and, as a result, the pathology of the cardiovascular system may be exposure to mercury. The aim of study is to study the relationship between ED markers in individuals exposed to mercury. Materials and methods. A survey was carried out using biochemical and statistical methods in persons exposed to mercury with more than five years of work experience, and in patients with chronic mercury intoxication in the long-term post-exposure period. Results. Relationships of biochemical indicators of ED of various directions have been established, indicating the presence of pathological changes in the endothelium of vessels in which its different links are involved. Conclusions. Associations were established between the exposition load and the concentration of ED markers in workers without occupational disease, which indicates the contribution of production factors to its formation during contact with the toxicant. The results of the study of the correlation of biochemical indicators of ED indicate the presence of complex associations that form a closed system between its markers at the stage before the formation of occupational disease, and their disunity in the distant period of chronic mercury intoxication, especially in the presence of CVD.

Obstructive sleep apnea syndrome: functional state of vascular endothelium and features of brain hemodynamics

The aim of the study is to identify the relationships between the functional state of vascular endothelium and regional cerebral blood flow in people of working age with moderate to severe obstructive sleep apnea syndrome. A transverse prospective observational study was conducted. It included 24 patients. Among them were 16 patients of working age with moderate to severe obstructive sleep apnea syndrome who were included in the main study group and 8 patients without sleep disorders in the control group according to polysomnography. The levels of biochemical markers of endothelial dysfunction, the indicators of endothelium-dependent vasodilation of the brachial artery were determined. Single-photon emission computed tomography of the brain was performed using 99mTc-hexamethylpropyleneaminoxime. In the patients of working age with moderate to severe obstructive sleep apnea syndrome, significantly lower average group values of the serum nitric oxide level of 11.7 (6.25‒18.30) μmol/l were detected versus 34.4 (25.33‒41.70) μmol/l in the control group, p &lt; 0.01), as well as higher homocysteine concentrations of 19.4 (15.13‒23.76) μmol/l versus 11.6 (6.40‒ 14.71) μmol/l in the control group, p &lt; 0.05, sP-selectin 176 (142.0‒189.0) ng/ml versus 122 (113.3‒168.5) ng/ml in the control group, p &lt; 0.05, and sE β-selectin 78 (69.0‒121.0) ng/ml versus 52 (43.1‒73.3) ng/ml in the control group, p &lt; 0.05. The data on the correlation of the level of neurohumoral markers of endothelial dysfunction of sP-selectin (p &lt; 0.01) and sE-selectin (p &lt; 0.05) with the degree of impaired regional cerebral blood flow were obtained. A direct relationship was found between the markers of endothelium-dependent vasodilation and regional cerebral blood flow in the frontal segments (p &lt; 0.05), the temporal segment on the right (p &lt; 0.05).

Serum concentration of selected biochemical markers of endothelial dysfunction and inflammation in patients with the varying activity of inflammatory bowel disease.

Endothelial dysfunction leads to an increased expression of cell adhesion molecules, leukocyte diapedesis, vascular smooth‑muscle tone, excessive permeability of vascular walls, and increased procoagulant activity. We investigated whether serum levels of several endothelial and platelet activation markers correlated with disease activity in patients with inflammatory bowel disease (IBD). This study included 56 patients with ulcerative colitis, 66 with Crohn disease, and 40 healthy controls. We measured the complete blood count and levels of fibrinogen, C‑reactive protein, albumin, interleukin 6, tumor necrosis factor α, E‑selectin, P‑selectin, monocyte chemoattractant protein 1 (MCP‑1), soluble CD40 ligand (sCD40L), and microparticles. There were no significant differences in the median levels of E‑selectin, P‑selectin, MCP‑1, sCD40L, and microparticles between patients with active IBD, those with inactive IBD, and healthy controls. The clinical disease activity assessed with the Mayo scale in the ulcerative‑colitis group was weakly, positively correlated with sCD40L (R = 0.32, P = 0.02), P‑selectin (R = 0.32, P = 0.02), and inflammatory marker levels. The clinical disease activity index in the Crohn disease group was positively correlated with the markers of inflammation yet not with the markers of endothelial activity. E‑selectin, P‑selectin, sCD40L, MCP‑1, and microparticle levels do not significantly differ between patients with the varying activity of IBD. However, due to the observed correlations, further studies of a larger patient group should be conducted to confirm our observations.

Microcirculation and biochemical markers of endothelial dysfunction after medical and surgical treatment in patients with peripheral arterial disease

Introduction . Тhe peripheral (PAD) arteries of lower extremities are most commonly suffers from the peripheral arterial disease that can be asymptomatic for a long time. Late clinical manifestation leads to reduction the quality of life and is often accompanied by limbs amputation. These cases are frequent when revascularization is not possible. The development of chronic limb ischemia (CLI) is associated with endothelial dysfunction (ED), oxidative stress and inflammation. The aim of this work is to study skin microcirculation and laboratory markers of ED in patients with PADs before and after medical treatment or operations. Materials and methods . The study included 17 healthy people (44–61 years old) and 38 patients (58–75 years old) with PAD, which were divided into four groups in accordance with the stage of CLI. The research protocol included biochemical and instrumental research methods to determine the functional status of the microcirculation system. Results . Significant differences in the values of biochemical markers and the results of instrumental studies of ED were obtained in groups with PAD compared with the control group. The study was fully repeated two weeks after treatment. It revеals that direct endovascular and reconstructive methods for revascularization of the lower extremities, simultaneous or staged elimination of the pathological focus, complex conservative therapy are accompanied by a decrease in laboratory markers of ED and inflammation and an improvement in micro vessel regulation due to the neurogenic and endothelial mechanisms. The most significant differences were obtained in the group with atherosclerosis of low limb vessels, namely the von Willebrand factor (from 180±56 % before the treatment to 128±36 % after), endothelin (0.37±0.15 pmol/l before the treatment to 0.20±0.08 pmol/l) after, homocysteine (from 15±3 mcmol/l to 10±2 mcmol/l). Conclusions . It was found that the recovery of the main blood flow is accompanied by an improvement in the function of the microcirculation system, which can be detected both by specific biomechanical markers and instrumental methods for diagnosing ED.

Особливості взаємозв'язків між показниками функціонального стану серцево-судинної системи та біохімічними маркерами ендотеліальної дисфункції у дітей з дисплазією сполучної тканини

Особливості взаємозв'язків між показниками функціонального стану серцево-судинної системи та біохімічними маркерами ендотеліальної дисфункції у дітей з дисплазією сполучної тканини

P872Activity of nonspecific systemic inflammation and biochemical markers of endothelial dysfunction as the criteria of coronary heart disease destabilization

Abstract Introduction Nonspecific systemic inflammation (NSSI) as well as endothelial dysfunction (EDF) plays an important role in the development and progression of coronary heart disease (CHD). Its exacerbation can cause the atherosclerotic plaque damage and the CHD progression with development of atherothrombotic complications. Purpose To evaluate the activity of nonspecific systemic inflammation and biochemical markers of endothelial dysfunction and their diagnostic significance in CHD patients as the criteria of disease destabilization. Methods The study included 173 CHD patients (the average age was 57.24±5.12 years). 92 patients were with stable angina (45 with 2nd and 47 with 3rd functional classes) and 81 patients were with acute coronary syndromes (ACS) (43 with unstable (progressive) angina and 38 – with acute myocardial infarction). The study excluded patients with severe chronic heart failure, liver and kidney dysfunction, acute or chronic inflammatory diseases, diabetes mellitus, severe obesity, infectious diseases. The control group included 30 healthy subjects (average age was 55.37±4.82 years). Activity of NSSI was assessed by the concentration of high sensitive C-reactive protein (hsCRP), tumor necrosis factor-α (TNF-α) and pregnancy-associated plasma protein A (PAPP-A) as a marker of endogenic destruction, which were determined by ELISA. EDF was assessed by the concentration of endothelin-1 (ET-1) and soluble vascular cell adhesion molecules (sVCAM) using ELISA method. Results CHD patients were characterized by significant increasing of hsCRP, TNF-α, PAPP-A levels regarding to control group (5.29±0.19 and 0.87±0.04 mg/L for hsCRP, respectively, p&lt;0.001; 4.28±0.18 and 1.18±0.07 ng/mL for TNF-α, respectively, p&lt;0.001; 9.81±0.16 and 3.12±0.42 mIU/L for PAPP-A, respectively, p&lt;0.01), which was the evidence of NSSI activation. Levels of both ET-1 and sVCAM-1 in CHD patients were more than twice higher than in the control group (9.89±0.28 and 4.01±0.36 ng/mL for ET-1, respectively p&lt;0.001; 1442.9±25.3 and 626.0±34.1 ng/mL for sVCAM, respectively, p&lt;0.001). Levels of biochemical markers of both NSSI and EDF increased with an increase in disease severity (p&lt;0.01) and the most severe changes were in patients with ACS, especially in patients with acute myocardial infarction. Significant relationships were between levels of both ET-1 and sVCAM with both hsCRP and TNF-α. Significant relationships were between PAPP-A level with both hsCRP and TNF-α, but were absent with both ET-1 and sVCAM levels. Therefore, we believe that the endogenic destruction of plaque is more related with activation of NSSI than with progression of EDF. Conclusion The severity of the CHD is associated with the degree of both activation of nonspecific systemic inflammation and dysfunction of vascular endothelium. Elevated production of these markers can be considered as the indicator of both atherosclerotic plaque damage and the possibility of ACS development.

РОЛЬ СПІВВІДНОШЕННЯ PLGF/SFLT-1 У ПРОГНОЗУВАННІ ПРЕЕКЛАМПСІЇ (ОГЛЯД ЛІТЕРАТУРИ)

Ендотеліальна судинна дисфункція є важливою ланкою патогенезу прееклампсії – патологічного стану, який займає провідне місце в структурі материнської захворюваності та смертності, перинатальної смертності та внутрішньоутробної затримки розвитку плода. В даний час оцінка стану судинного ендотелію під час вагітності– інформативний метод прогнозування розвитку даного захворювання. У статті підсумовані дані про значимість найбільш вивчених специфічних біохімічних маркерів ендотеліальної дисфункції, а саме: розчинної fms-подібної тирозинкінази-1 (sFlt-1) та плацентарного фактору росту (PlGF), у прогнозуванні та діагностиці прееклампсії. Оскільки етіопатогенез прееклампсії обумовлений розвитком ендотеліальної недостатності і порушенням формування судин в системі матір-плацента-плід, тому вибір в якості скринінгових тестів даних біомаркерів ангіогенезу виправданий з логічної точки зору. У жінок із патологічним перебігом гестаційного процесу в 92,5% випадків вже за кілька тижнів до появи перших клінічних симптомів спостерігається зниження концентрації PlGF та значне підвищення концентрації sFlt-1, що дає змогу визначити ризик гестозу задовго до появи його тяжких клінічних проявів та розробити оптимальну тактику ведення пацієнтів з даною патологією. В якості скринінгового показника ризику розвитку прееклампсії найбільш достовірне визначення співвідношення sFlt-l/PIGF, що відбиває зміну обох біомаркерів при прееклампсії більш виражено, ніж окреме визначення будь-якого з цих факторів. Дана тема є актуальною, оскільки поширеність прееклампсії за даними різних авторів варіює від 3 до 8% серед вагітних в розвинених країнах. В цілому до 10-15% материнських смертей пов'язані з прееклампсією і еклампсією.

Correlation between biochemical markers of endothelial dysfunction, free radical oxidation and morphometric parameters of macular retina in pregnant women with preeclampsia

To study the relationship between biochemical indexes of blood serum, lacrimal fluid (LF) and the macular retinal volume (MRV) in pregnant women with preeclampsia. The study included 42 pregnant women aged 21 to 40 years with preeclampsia of different severity (the main group): 1st subgroup - mild degree (22 people); 2nd subgroup - average degree (12 people); 3rd subgroup - severe degree (8 people). The comparison group included 20 pregnant women aged 19 to 38 years experiencing physiologically natural pregnancy. By the 3rd trimester, in the 1st subgroup the index of MRV was between 6.4 and 9.5 mm3; the index of von Willebrand factor (vWF) - 88.9±7.3%; endothelin (ET) content in LF was 1.35±0.2 ng/ml; the indices of free radical oxidation (FRO) in lacrimal fluid (Ssp and Sind) were significantly higher than in the comparison group (p<0.01). In the 2nd subgroup: MRV was 7.4±0.5 mm3, ET - 2.2±0.3 ng/ml, and vWF - 117.2±8.5% (p<0.01); the indices of FRO were higher in comparison with the 1st subgroup. In the 3rd subgroup: MRV was 8.5±0.7 mm3, ET - 3.2±0.3 ng/ml, and vWF - 157±9.5% (difference with the 2nd subgroup p<0.01). The indices of FRO (Ssp, Sind and h) indices were maximum high (difference with the 2nd subgroup p<0.01). A trend of increase of MRV by the 3rd trimester correlating with the degrees of preeclampsia severity was found. In the main group (r from 0.71 to 0.83), strong, direct, statistically significant association was found between the increase of ET levels in LF, vWF and MRV on the one side, and FRO on the other side.

Endothelial function changes in paroxysmal atrial fibrillation and treatment with propafenone

Aim. To evaluate the changes of endothelial function in arterial hypertension (AH) patients with paroxysmal atrial fibrillation (AF) in treatment with propafenone (Propanorm, PRO.MED.CS Praha a. s.) in comparison with bisoprolol.Material and methods. To the study, 62 AH patients included with paroxysmal AH, age 45-63 y. o. (mean age 54,5±3,7 y. o.). Patients were randomized to 2 groups: 32 of group 1 (main) for rhythm-control were taking propafenone (Propanorm, PRO.MED.CS Praha a. s.) 450 mg daily, and 30 of group 2 (comparison) were taking bisoprolol for rate control. The groups were comparable by gender, age, severity of AH and duration of arrhythmia. Changes in endothelium vascular motion function and biochemical markers of endothelial dysfunction were assessed at inclusion and in 12 months of therapy.Results. Sinus rhythm retention in propafenone group facilitated the improvement of vascular motion function of endothelium — endothelium dependent vasodilatation of brachial artery showed tendency to rise significantly from 5,4±0,3% to 6,9±0,1% (р=0,01). In patients taking bisoprolol for pulse reduction during 12 months, there was negative tendency from 4,8±0,2% to 3,6±0,1% (р=0,003), that points on worsening of endothelial function with persistent AF. Repeat measurement of biochemical markers of endothelial dysfunction revealed that in 12 months there is raise of endothelin concentration in both groups. Value of the collagen-binding activeness of von Willebrand factor in 12 months significantly reduced from 131±12 to 118±6 U/dL (р&lt;0,05) in those retaining sinus rhythm with propafenone, and increased from 135±11 U/dL to 147±12 U/dL in those with rate control by bisoprolol.Conclusion. In AH patients with paroxysmal AF retention of sinus rhythm with propafenone facilitated the improvement of vascular motion function of endothelium and decrease of collagen binding activeness of von Willebrand factor.

Biochemical markers of hypertension, prehypertension

ObjectiveThere are insufficient researches aimed at evaluating biochemical markers of mechanisms of formation of AH and lesion of target organs in hypertension and prehypertension. The aim of that research was to study the level of endothelial dysfunction markers and damage to the cardiovascular system in hypertension and prehypertension. Patients and methodsA cross-sectional study was performed among 938 people aged 18 to 65 years. All respondents were surveyed, blood pressure measured, for glucose, cholesterol, interleukin-6, sFAS, LIGHT, hFABP, NT-ProBNP and an Endocan concentrations were tested. Depending on the level of blood pressure participants were splitted into groups with normotension, prehypertension and hypertension. ResultsComparing the markers of inflammation, apoptosis and target organ damage in the prehypertensive group, the level of the LIGHT protein was Me=265.2pg/ml (Q25–Q75: 197.7–444.3), in the control group — Me=251.1pg/ml (Q25–Q75: 176.6–376.6), the Endocan level was Me=660.6pg/ml (Q25–Q75: 419.6–867.4) and in the control group Me=587.5pg/ml (Q25–Q75: 401.9–838.1). In the AH group, the level of the LIGHT Me=273.1pg/ml (Q25–Q75: 195.1–455.2), Endocan Me=668.2pg/ml (Q25–Q75: 434.8–977.3), heart-type fatty-acid-binding protein Me=2233.1pg/ml (Q25–Q75: 1518.4–3391.1) exceeded the control group. ConclusionThus, the development of prehypertension and hypertension is characterized by an increase in the activity of biochemical markers of endothelial dysfunction and damage to target organs, more expressed in the presence of hypertension.

Endothelial dysfunction and reduced heart rate variability in patients with metabolic syndrome

According to experts of the World Health Organization (WHO), metabolic syndrome (MS) can be considered as pandemy of the XXI century, because its prevalence among the population of developed countries is about 25-35%. In this study with the purpose of complex investigation of the autonomic nervous system and endothelial function we included 66 patients with MS between the ages of 25 and 61 (46.9±9.9 years). A comparison group of apparently healthy individuals (16 individuals, average age of 45.3±2.3 years; P&gt;0.05) was studied. To evaluate the response of microvascular tone, we used the method of wavelet analysis of skin temperature oscillations during cooling of the limb. All patients underwent the study of heart rate variability. The levels of insulin, endothelin-1, and vascular endothelial growth factor were determined using enzyme immunoassay. Patients with MS had significant differences in all metabolic parameters. Our study showed that in the group of MS there is a decrease of the variability of heart rhythm compared with the healthy group. Conducting cold test revealed signs of endothelial dysfunction in the MS group, which was manifested by the decrease of the index of vasodilation in the endothelial and neurogenic frequency range. In the study group we determined the increase in biochemical markers of endothelial dysfunction, which correlated with parameters of vasodilation. Also, the presence of endothelial dysfunction significantly correlated with signs of reduction of the variability of the heart rhythm.