Endothelium-dependent Flow-mediated Dilation Research Articles

Chronic endothelial dopamine receptor stimulation improves endothelial function and hemodynamics in autosomal dominant polycystic kidney disease

Altered polycystin-mediated endothelial flow mechanosensitivity contributes to the development of hypertension and cardiovascular complications in patients with autosomal dominant polycystic kidney disease (ADPKD). Stimulation of endothelial type 5 dopamine receptors (DR5) can acutely compensate for the endothelial consequences of polycystin deficiency, but the chronic impact of this approach must be evaluated in ADPKD. Nineteen patients with ADPKD on standard of care therapy were randomized to receive a 2-month treatment with the DR agonist rotigotine using transdermal patches, nine at 2 mg/24hours and ten at 4 mg/24hours or while ten were untreated. Rotigotine at the dose of 4 mg/24hours significantly increased nitric oxide release (nitrite levels from 10±30 to 46±34 nmol/L) and radial artery endothelium-dependent flow-mediated dilatation (from 16.4±6.3 to 22.5±7.3%) in response to hand skin heating. Systemic hemodynamics were not significantly modified but aplanation tonometry showed that rotigotine at 4 mg/24hours reduced aortic augmentation index and pulse pressure without affecting carotid-to femoral pulse wave velocity. Plasma creatinine and urea, urinary cyclic AMP, which contributes to cyst growth in ADPKD and copeptin, a surrogate marker of vasopressin, were not affected by rotigotine. In mice with a specific deletion of polycystin-1 in endothelial cells, chronic infusion of the peripheral DR5 agonist fenoldopam also improved mesenteric artery flow-mediated dilatation and reduced blood pressure. Thus, our study demonstrates that in patients with ADPKD, chronic administration of rotigotine improves conduit artery endothelial function through the restoration of flow-induced nitric oxide release as well as hemodynamics suggesting that endothelial DR5 activation may represent a promising pharmacological approach to prevent cardiovascular complications of ADPKD.

Endothelial Dysfunction and Pre-Existing Cognitive Disorders in Stroke Patients.

The origin of pre-existing cognitive impairment in stroke patients remains controversial, with a vascular or a degenerative hypothesis. To determine whether endothelial dysfunction is associated with pre-existing cognitive problems, lesion load and biological anomalies in stroke patients. Patients originated from the prospective STROKDEM study. The baseline cognitive state, assessed using the IQ-CODE, and risk factors for stroke were recorded at inclusion. Patients with an IQ-CODE score >64 were excluded. Endothelial function was determined 72 h after stroke symptom onset by non-invasive digital measurement of endothelium-dependent flow-mediated dilation and calculation of the reactive hyperemia index (RHI). RHI ≤ 1.67 indicated endothelial dysfunction. Different biomarkers of endothelial dysfunction were analysed in blood or plasma. All patients underwent MRI 72 h after stroke symptom onset. A total of 86 patients were included (52 males; mean age 63.5 ± 11.5 years). Patients with abnormal RHI have hypertension or antihypertensive treatment more often. The baseline IQ-CODE was abnormal in 33 (38.4%) patients, indicating a pre-existing cognitive problem. Baseline IQ-CODE > 48 was observed in 15 patients (28.3%) with normal RHI and in 18 patients (54.6%) with abnormal RHI (p = 0.016). The RHI median was significantly lower in patients with abnormal IQ-CODE. Abnormal RHI was associated with a significantly higher median FAZEKAS score (2.5 vs. 2; p = 0.008), a significantly higher frequency of periventricular lesions (p = 0.015), more white matter lesions (p = 0.007) and a significantly higher cerebral atrophy score (p < 0.001) on MRI. Vascular biomarkers significantly associated with abnormal RHI were MCP-1 (p = 0.009), MIP_1a (p = 0.042), and homocysteinemia (p < 0.05). A vascular mechanism may be responsible for cognitive problems pre-existing stroke. The measurement of endothelial dysfunction after stroke could become an important element of follow-up, providing an indication of the functional and cognitive prognosis of stroke patients.

The relationship between endothelial-dependent flow-mediated dilation and diastolic function in type 2 diabetes

The relationship between endothelial-dependent flow-mediated dilation and diastolic function in type 2 diabetes

Effect of Oral Care on Endothelial Dysfunction in Patients with Acute Coronary Syndrome.

Periodontitis is a common chronic infection and is associated with cardiovascular disease. This study evaluated whether basic oral care for periodontal disease could improve endothelial function in patients with acute coronary syndrome (ACS).This study enrolled 54 patients with acute coronary syndrome admitted to Kagoshima City Hospital and who had undergone percutaneous coronary intervention. Flow-mediated endothelium-dependent dilatation (FMD) was measured before discharge (initial FMD) and at 8 months after percutaneous coronary intervention (follow-up FMD). The following periodontal characteristics were measured: periodontal pocket depth (PPD, mm), plaque control record (%), and bleeding on probing (%). All patients received basic oral care instructions from dentists. The oral health condition was generally poor in the participants and there were 24 patients (44.4%) who had severe PPD. Despite the intervention of basic oral care, the periodontal characteristics did not improve during the study period; initial FMD and follow-up FMD did not significantly differ (4.38 ± 2.74% versus 4.56 ± 2.51%, P = 0.562). However, the follow-up FMD was significantly lower in patients with severe PPD (≥ 6.0 mm, n = 24) than in patients without severe PPD (≤ 5.0 mm, n = 30) (FMD: 3.58 ± 1.91% versus 5.37 ± 2.67%, P = 0.007). FMD tended to be worse in patients with severe PPD than in patients without severe PPD (ΔFMD: -0.55 ± 2.12 versus 0.81 ± 2.77 %, P = 0.055). In conclusion, during the use of basic oral care, endothelial function improved in patients without severe PPD, while it worsened in patients with severe PPD.

The effects of water-based circuit exercise training on vascular function in people with coronary heart disease.

Impaired endothelial function in people with coronary heart disease (CHD) is associated with increased mortality. Water immersion can increase peripheral artery shear stress which may provide an additional stimulus to the endothelium during exercise. This study compared the effects of water-based circuit exercise training (WEX) and gym-based circuit exercise training (GEX) on vascular function in people with stable CHD. Participants were randomised to 12 weeks of WEX (n=20), GEX (n=20) or a control group (usual activities; n=12). Endothelium-dependent flow-mediated dilation (FMD) and glyceryl trinitrate-mediated dilation (GTN) of the brachial artery were assessed pre- and post-intervention. FMD increased following WEX [4.0% (3.0-5.1%) to 5.3% (4.1-6.5%); p=0.016], but was unchanged following GEX [4.9% (3.8-5.9%) to 5.0% (3.8-6.1%); p=0.822]. There were no between-group differences in the change in FMD and no significant changes in GTN-mediated dilation percentage. Triglycerides decreased following GEX [1.2 mmol.L-1 (1.0-1.4 mmol.L-1) to 1.0 mmol.L-1 (0.8-1.3 mmol.L-1); p=0.022], but there were no further differences in lipid profiles. WEX improved endothelial function of the brachial artery in people with stable CHD, suggesting that WEX is an effective alternative to gym-based exercise in people living with CHD, which may specifically address vascular health.

Kolekalsiferol sonrası endotel disfonksiyonu ve damar sertliğinin diyaliz modalitesine göre değerlendirilmesi

ABSTRACT&#x0D; Objective: The risk of developing cardiovascular disease (CVD) increases significantly in children with chronic kidney disease (CKD) especially with low serum 25- hydroxyvitamin D (25OHD) levels. Herein; we aimed to compare the effects of vitamin D deficiency and the impact of cholecalciferol treatment on endothelial functions and vascular stiffness in children with CKD receiving hemodialysis (HD), peritoneal dialysis (PD) and non- dialysis(ND).&#x0D; Methods: 7 HD, 7 PD and 27 ND patient groups consisting of 41 children totally with low 25OHD levels were compared among each other in regards of biochemical parameters, flow-mediated dilatation(FMD) and local arterial stiffness before and after a single dose of 300.000 units of cholecalciferol treatment.&#x0D; Results: There was no difference in FMD and local arterial stiffness values between HD, PD and ND patient groups before vitamin D supplementation. Significant increase in endothelium-dependent FMD was observed in all patient groups after intervention with cholecalciferol; however the improvement in endothelium-independent FMD and local arterial stiffness measurements was demonstrated in patients with PD and ND. Baseline parathormon level was higher in patients on dialysis; at the end of the study, significant decrease was detected only in patient group not receiving diaysis.&#x0D; Conclusions: Endothelial dysfunction and impaired vascular stiffness were determined in children with CKD with low 25OHD levels regardless of the disease severity.. Recovery with cholecalciferol therapy revealed that vitamin D deficiency should be corrected even in early stages of CKD to prevent the development of CVD

Pulmonary rehabilitation and endothelial function in patients with chronic obstructive pulmonary disease: A prospective cohort study

BackgroundChronic obstructive pulmonary disease (COPD) is associated with subclinical atherosclerosis and endothelial dysfunction, thereby leading to increased cardiovascular risk. In the present study, we evaluated the changes in endothelium-dependent flow-mediated dilation (FMD) in a cohort of severe COPD patients undergoing pulmonary rehabilitation. MethodsConsecutive COPD patients referred to our Pulmonary Rehabilitation Unit were screened for inclusion. All study procedures were performed at hospital admission and discharge. ResultsOf 78 patients screened for eligibility, a total of 40 participants (67.5% males, median age 72.5 years) were included. After pulmonary rehabilitation, a significant improvement in functional parameters, exercise capacity, and measures of disability and quality of life were documented. FMD changed from 3.25% (IQR: 2.31–4.26) to 4.95% (IQR: 3.57–6.02), corresponding to a 52.3% increase of its median value (P < 0.001). Significantly lower changes in FMD were documented in COPD patients with hypercholesterolemia as compared to those without (+0.33% ± 1.61 vs. +1.62% ± 1.59, P = 0.037). Changes in FMD (ΔFMD) were positively associated with changes in forced expiratory volume in 1 s (FEV1), when expressed both as absolute values (ΔFEV1) (r = 0.503, P = 0.002) and as percentages of predicted values (ΔFEV1%) (r = 0.608; P < 0.001). In multiple linear regressions, after adjusting for major cardiovascular risk factors, ΔFEV1 (β=0.342; P = 0.049) and ΔFEV1% (β=0.480; P = 0.015) were both confirmed as independent predictors of ΔFMD. ConclusionsResults of our study suggest that endothelial function may improve in COPD after pulmonary rehabilitation. The potential beneficial effect in terms of cardiovascular risk prevention should be evaluated in ad hoc designed studies.

A study of the relationship between brachial artery vasodilation and platelet/lymphocyte ratio in diabetic patients with coronary atherosclerosis.

To investigate the correlation between brachial artery flow-mediated endothelium-dependent dilation (FMD) and platelet-lymphocyte ratio (PLR) in peripheral blood and coronary atherosclerosis in diabetic patients. Seventy-five diabetic patients aged 62 ± 9 years, 68% male and 32% female, who underwent brachial artery endothelial function test and coronary CT scan were collected. Coronary artery calcification (CAC) was observed to assess the presence of coronary atherosclerosis, and high-resolution extravascular ultrasound was used to detect FMD. Platelet count and lymphocyte count were recorded by routine blood tests, and PLR was calculated for each study subject. Statistical methods were used to verify the association of FMD and PLR with CAC assessed by CT, respectively. Patients with coronary atherosclerosis had decreased FMD and increased PLR compared with patients with normal coronary arteries. Univariate logistic regression analysis showed that CAC score was significantly associated with both FMD (odds ratio: 0.167; 95% confidence interval: 0.049-0.565; p = 0.002) and PLR (odds ratio: 0.127; 95% confidence interval: 0.033-0.484; p = 0.001) at FMD < 5.1% or PLR > 130. The area under the ROC curve of FMD and PLR alone was 0.760 and 0.763, respectively. In addition, combined diagnosis of FMD and PLR showed the highest area under the ROC curve (0.830). FMD combined with PLR is expected to be a precise diagnostic modality for coronary artery calcification in diabetic patients.

Evaluation of Peripheral Vascular Function After Distal Radial Artery Access for Invasive Percutaneous Coronary Procedures

Abstract Objective: The aim of this study is to investigate the difference in impact between distal transradial access (dTRA) and classical transradial access (TRA) on vascular function using flow-mediated vasodilation (FMD) following coronary diagnostic and therapeutic catheterizations. Methods: The analysis involves a non-randomized inclusion of patients undergoing either diagnostic or elective percutaneous coronary intervention, using a dTRA access or a conventional standard TRA. Two hours after the procedure ended, the endothelium-dependent flow-mediated dilation of the brachial artery was measured by ultrasound. Results: A total number of 50 patients were included. There was no statistically significant difference between the two groups (7.20% vs 6.99%, p &lt; 0.09 for non-inferiority). Additionally, there were higher baseline values observed for BA diameters in the conventional approach group. Regarding the other secondary endpoints, there were no major access site complications, radial occlusion, in-hospital major bleeding or severe arterial spasm recorded in both groups. Conclusion: Compared to conventional TRA, accessing distal radial artery for diagnostic and therapeutic coronary interventions has the same impact on short-term vascular endothelial function and was safely performed without any major vascular complications.

Effect of exercise on vascular function in hypertension patients: A meta-analysis of randomized controlled trials.

The purpose of this study was to systematically evaluate the effect of exercise on vascular function in patients with pre- and hypertension. A systematic review of articles retrieved via the PubMed, Embase, EBSCO, and Web of Science databases was conducted. All the randomized controlled trials published between the establishment of the databases and October 2022 were included. Studies that evaluated the effects of exercise intervention on vascular function in patients with pre- and hypertension were selected. A total of 717 subjects were included in 12 randomized controlled trials. The meta-analysis showed that in patients with pre- and hypertension, exercise can significantly reduce systolic blood pressure (SBP) (MD = -4.89; 95% CI, -7.05 to -2.73; P < 0.00001) and diastolic blood pressure (DBP) (MD = -3.74; 95% CI, -5.18 to -2.29; P < 0.00001) and can improve endothelium-dependent flow-mediated dilatation (MD = 2.14; 95% CI, 1.71-2.61; P < 0.00001), and exercise did not reduce pulse wave velocity (PWV) (MD = 0.03, 95% CI, -0.45-0.50; P = 0.92). Regression analysis showed that changes in exercise-related vascular function were independent of subject medication status, baseline SBP, age and duration of intervention. Aerobic, resistance, and high-intensity intermittent exercise all significantly improved SBP, DBP, and FMD in pre- and hypertensive patients, however, they were not effective in reducing PWV, and this effect was independent of the subject's medication status, baseline SBP, age and duration of intervention. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022302646.

Association between atherogenic risk-modulating proteins and endothelium-dependent flow-mediated dilation in coronary artery disease patients

PurposeEndothelial dysfunction is an early and integral event in the development of atherosclerosis and coronary artery disease (CAD). Reduced NO bioavailability, oxidative stress, vasoconstriction, inflammation and senescence are all implicated in endothelial dysfunction. However, there are limited data examining associations between these pathways and direct in vivo bioassay measures of endothelial function in CAD patients. This study aimed to examine the relationships between in vivo measures of vascular function and the expression of atherogenic risk-modulating proteins in endothelial cells (ECs) isolated from the radial artery of CAD patients.MethodsFifty-six patients with established CAD underwent trans-radial catheterization. Prior to catheterization, radial artery vascular function was assessed using a) flow-mediated dilation (FMD), and b) exercise-induced dilation in response to handgrip (HE%). Freshly isolated ECs were obtained from the radial artery during catheterization and protein content of eNOS, NAD(P)H oxidase subunit NOX2, NFκB, ET-1 and the senescence markers p53, p21 and p16 were evaluated alongside nitrotyrosine abundance and eNOS Ser1177 phosphorylation.ResultsFMD was positively associated with eNOS Ser1177 phosphorylation (r = 0.290, P = 0.037), and protein content of p21 (r = 0.307, P = 0.027) and p16 (r = 0.426, P = 0.002). No associations were found between FMD and markers of oxidative stress, vasoconstriction or inflammation. In contrast to FMD, HE% was not associated with any of the EC proteins.ConclusionThese data revealed a difference in the regulation of endothelium-dependent vasodilation measured in vivo between patients with CAD compared to previously reported data in subjects without a clinical diagnosis, suggesting that eNOS Ser1177 phosphorylation may be the key to maintain vasodilation in CAD patients.

Intensive Periodontal Treatment Does Not Affect the Lipid Profile and Endothelial Function of Patients with Type 2 Diabetes: A Randomized Clinical Trial.

Background: Local eradication of periodontal infection could potentially have a much broader impact on the diabetic condition by also contributing to the modification of the lipid profile, which is directly compromised in the alteration of endothelium-dependent vasodilation. The aim of this trial was to assess the benefits of intensive periodontal treatment (IPT) on the lipid profile and endothelial function of diabetic patients. Methods: This was a 6-month, randomized controlled trial involving diabetic patients with generalized periodontitis. The study group comprised 290 individuals who were randomly assigned to receive Intensive Periodontal Treatment (IPT, Intervention Group) or conventional adult prophylaxis (Control Periodontal Treatment, CPT, Control Group). Outcomes encompassed lipid profile involving serum total cholesterol, serum triglyceride, low-density lipoprotein cholesterol, high-density lipo-protein cholesterol, and flow-mediated vasodilation (FMD) as an index of endothelium-dependent vasodilation (primary outcomes); periodontal indices and high-sensitive C-reactive protein were evaluated at baseline, 3 and 6 months after periodontal treatment. Results: An increase in endothelium-dependent flow-mediated dilatation (FMD) was observed in the Intensive Periodontal Treatment group in comparison with Control (p < 0.001), but results are not statistically different. There were no differences in lipid profile in individuals of both groups. Conclusions: An intensive periodontal treatment might improve endothelial function, suggesting a direct beneficial effect on the vasculature, possibly mediated by systemic inflammatory reduction. However, no statistically significant differences between groups were observed, and no benefits were proved on lipid profile.

Association of sleep-wake rhythm and sleep quality with endothelial function in young adults.

ObjectiveThe environment in modern society could disturb the sleep-wake rhythm. We aimed to study the association of sleep-wake rhythm with endothelial function and sleep quality.Material and MethodsThirty-one healthy university students (mean age: 20.4±1.8 years) were enrolled. The endothelial function was evaluated with the percent endothelium-dependent flow-mediated dilation of the brachial artery [%FMD: (maximum diameter - baseline diameter)/baseline diameter x 100] using the high-resolution ultrasonography. We also measured the total sleep time (TST), sleep effciency, and the standard deviation (SD) of sleep timing (midpoint between bedtime and wake-up time) using the actigraphy. The irregular sleep-wake rhythm was defined as having the shift of bedtime or wake-up time for two hours or longer.ResultsThe %FMD and sleep efficiency were significantly lower in the irregular group than regular group (%FMD: 6.1±2.4 vs. 10.9±2.3, p<0.001, sleep effciency: 92.2±5.8 vs. 95.9±2.8%, p=0.027), whereas there was no significant difference in %FMD between the two groups of TST <6 hours and TST ≥6 hours. The %FMD was significantly correlated with SD of sleep timing (r=-0.481, p=0.006). Multiple regression analyses, including age, sex, TST, sleep effciency, and SD of sleep timing revealed that the SD of sleep timing was a significant factor associated with %FMD (ß=-0.454, p=0.017).ConclusionOur findings suggest that the irregular sleep-wake rhythm and poor sleep quality could have adverse effects on endothelial function in young adults.

Clinical Effect of Digital Subtraction Angiography Combined with Neurointerventional Thrombolysis for Acute Ischemic Cerebrovascular Disease and Its Influence on Vascular Endothelial Function and Oxidative Stress.

Objective Ischemic cerebrovascular disease is a commonly seen vascular disorder in clinical practice. Given the difficulty of drug therapy to achieve ideal curative effects, interventional therapy has gradually become the preferred treatment for the disease. This research primarily discusses the short-term efficacy of digital subtraction angiography- (DSA-) guided neurointerventional thrombolysis for acute ischemic cerebrovascular disease (AICVD) and its influence on vascular endothelial function (VEF) and oxidative stress (OS). Methods All the clinical data of 162 patients diagnosed with AICVD and treated between June 2019 and December 2021 were collected and analyzed retrospectively. They were assigned to two cohorts according to the difference in interventional methods: a conventional group (CG) given recombinant tissue plasminogen activator (rt-PA) therapy and an observation group (OG) intervened by DSA-guided neurointerventional thrombolysis. The two groups were compared with respect to short-term treatment efficacy, the National Institutes of Health Stroke Scale (NIHSS) score, cerebral hemodynamics, and VEF and OS indexes. Results The short-term efficacy was better in OG (93.98%) than in CG (82.28%). After treatment, the NIHSS score decreased in both cohorts with obvious differences within the group at different time points, and the posttreatment NIHSS score was lower in OG as compared to CG. OG had higher Qm and Vm while lower Wv, Zcv, and Rv than CG. Higher endothelial-dependent flow-mediated dilatation (FMD) was observed in OG, as well as lower ankle-brachial index (ABI) and pulse wave velocity (PWV). And the posttreatment MDA was lower while SOD, GSH-Px, and TAC were higher in OG compared with those on CG. All the above differences were of statistical significance (P < 0.05). Conclusions DSA-guided neurointerventional thrombolysis is highly effective in the treatment of AICVD, which can not only effectively improve patients' neurological function and cerebral hemodynamics but also mitigate VEF injury and help to alleviate patients' OS.

Effects of continuous hypoxia on flow-mediated dilation in the cerebral and systemic circulation: on the regulatory significance of shear rate phenotype

Emergent evidence suggests that cyclic intermittent hypoxia increases cerebral arterial shear rate and endothelial function, whereas continuous exposure decreases anterior cerebral oxygen (O2) delivery. To examine to what extent continuous hypoxia impacts cerebral shear rate, cerebral endothelial function, and consequent cerebral O2 delivery (CDO2), eight healthy males were randomly assigned single-blind to 7 h passive exposure to both normoxia (21% O2) and hypoxia (12% O2). Blood flow in the brachial and internal carotid arteries were determined using Duplex ultrasound and included the combined assessment of systemic and cerebral endothelium-dependent flow-mediated dilatation. Systemic (brachial artery) flow-mediated dilatation was consistently lower during hypoxia (P = 0.013 vs. normoxia), whereas cerebral flow-mediated dilation remained preserved (P = 0.927 vs. normoxia) despite a reduction in internal carotid artery antegrade shear rate (P = 0.002 vs. normoxia) and CDO2 (P < 0.001 vs. normoxia). Collectively, these findings indicate that the reduction in CDO2 appears to be independent of cerebral endothelial function and contrasts with that observed during cyclic intermittent hypoxia, highlighting the regulatory importance of (hypoxia) dose duration and flow/shear rate phenotype.

LINKAGE BETWEEN NOS3 (RS2070744) AND GNB3 (RS5443) GENES’ POLYMORPHISM, CAROTID ARTERIES STRUCTURAL CHANGES AND ENDOTHELIAL DYSFUNCTION IN ESSENTIAL HYPERTENSION

Objective: This study aims to verify the risk of endothelial dysfunction (ED) and carotid intima media thickness (IMT) changes depending on GNB3 (rs5443) and NOS3 (rs2070744) genes’ polymorphism in essential arterial hypertensives (EAH). Design and method: One-hundred EAH patients (moderate-very high cardiovascular risks, aged 45–65 years) and 48 practically healthy (control) participated in the case-control study. Soluble Vascular Cell Adhesion Molecule (sVCAM-1), total NO metabolites, transcriptional activity of NOS3 gene, Endothelium-Dependent Flow-Mediated Dilation of the Brachial Artery (FMD BA) and carotid IMT were studied. GNB3 (rs5443) and NOS3 (rs2070744) genotyping performed by TaqMan probes (CFx96ÔReal-Time PCR). Results: C-allele of NOS3 gene elevates the risk of atherosclerotic plaques on the carotid arteries over 3.5 times [OR95%CI:1.24–11.20; p = 0.019 and OR95%CI:1.22–10.18; p = 0.018], ED – by total NO metabolites decrease (&lt;25 mol/l) and sVCAM-1 value raise (&gt;1050 ng/ml) – 12 and 4 times [OR95%CI:1.23–112.7; p = 0.023 and OR95%CI:1.24–11.20; p = 0.019], respectively. Moreover, C-allele of NOS3 gene heighten the low NOS3 gene expression probability 69 times [OR95%CI:17,72–520,0; p &lt; 0,001]. The minor T-allele of GNB3 gene increases the risk of carotid arteries structural changes: by IMT (&gt;0,9 mm) – 3 times [OR95%CI:1.09–7.74; p = 0.027], atherosclerotic plaques – 10 and 5 times [OR95%CI:2.55–38.0; p &lt; 0.001 and OR95%CI:1.61–13.27; p = 0.003]. Besides, the T-allele of GNB3 gene enhances the high sVCAM-1 levels probability over 3 times [OR95%CI:1.06–9.59; p = 0.032]. Moderate and severe ED grades increase the risk of severe EAH 3 and 5.5 times [OR95%CI:1.13–9.34; p = 0.025 and OR95%CI:1.96–14.45; p &lt; 0.001]. The severe EAH course risk is associated more with the structural changes of the carotid arteries (IMT &gt; 0,9 mm increases the likelihood 3.5 times (p = 0.012), atherosclerotic plaques – 4 and 3.5 times (p &lt; 0,05) and decreased NOS3 gene expression – 3 times (p = 0.042), but not depend on separate ED markers (FMD BA, total NO metabolites or sVCAM-1). Conclusions: ED enhance the risk of severe EAH course 3–5.5 times. c-allele of NOS3 gene elevates the risk of both structural changes of the carotid arteries 3.5 times and particularly ED – 4–69 times. T-allele of GNB3 gene increases the risk of the carotid arteries structural changes more than ED – 3.5–4 vs 3 times as well.

ENDOTHELIUM DYSFUNCTION PATHWAY AND CAROTID INTIMA-MEDIA THICKNESS IN HYPERTENSIVE PATIENTS: ROLE OF NOS3 (RS2070744) AND GNB3 (RS5443) GENES’ POLYMORPHISMS

Objective: The crucial function of endothelium’s regulatory mechanisms is to maintain the balance between Monoxide Nitrogen (NO) release and endothelium-derived contracting factors production. Therefore, it is prognostically important to clarify the endothelial function (EF) deterioration pathway through the early biomarkers of EF and carotid intima media thickness (IMT) changes depending on GNB3 (rs5443) and NOS3 (rs2070744) genes’ polymorphism in essential arterial hypertension (EAH). Design and method: One-hundred EAH patients with hypertensive-mediated organ damage (moderate-very high cardiovascular risks, aged 45–65 years) and 48 practically healthy (control) participated in the cohort case-control study. Soluble Vascular Cell Adhesion Molecule (sVCAM-1), total NO metabolites (NO2-/NO3-), transcriptional activity of NOS3 gene, Endothelium-Dependent Flow-Mediated Dilation of the Brachial Artery (FMD BA) and carotid IMT were studied. GNB3 (rs5443) and NOS3 (rs2070744) genotyping performed by TaqMan probes (CFx96ÔReal-Time PCR). Results: The connections of NOS3 (rs2070744) with decreased total NO metabolites (F = 71.11; p &lt; 0.001), reduced NOS3 gene’s transcription activity (F = 8.71; p &lt; 0.001) and sVCAM-1 increase (F = 6.96; p = 0.002) were found, especially in the C-allele carriers (particularly in CC-genotype patients with lower total NO metabolites value – by 16.46% and 40.88% (p &lt; 0.001), lower transcription activity of NOS3 gene – 46.03% and 7 times (p &lt; 0.001), higher sVCAM-1 – 35.48% and 89.48% (p &lt; 0.001), respectively). ANOVA analysis didn’t confirm association of GNB3 (rs5443) gene with EF and carotid IMT. Severe EAH is associated with increased carotid IMT – 50.0% (p &lt; 0.001) and 57.14% (p &lt; 0.007), dilated carotid arteries – 17.36% (p = 0.012) and 21.79% (p = 0.004), decreased NOS3 gene’s transcription activity – 34.54% (p = 0.003). Severe structural carotid IMT changes in EAH patients (IMT &gt; 0.9 mm) is followed by higher blood pressure values (p &lt; 0.001), deterioration of EF: FMD BA decrease – 11.80% with compensatory increase of carotid arteries diameters – 17.38% and 21.99% (p &lt; 0.001) and serum sVCAM-1 concentration – by 20.49% (p = 0.005). Conclusions: NOS3 (rs2070744), but not GNB3 (rs5443) gene associate with endothelial function impairment and carotid IMT in EAH patients.

Examining the role of Drp1 in age‐related microvascular dysfunction

IntroductionAdvanced age is a well‐documented risk factor for coronary microvascular dysfunction. Recent evidence has underscored that advanced age is associated with a shift toward greater mitochondrial fission rather than mitochondrial fusion. Therefore, understanding key regulators of the balance of mitochondrial fission/fusion may help to identify the contribution of mitochondrial dynamics on microvascular endothelial function. DRP1 is a pro‐fission factor that has been linked to several disease manifestations including advanced age and cardiovascular disease (CVD).MethodsCoronary arteries were obtained from young control rats (YC, 15‐20 weeks) and old control rats (OC, 95‐100 weeks) and expression of DRP1 was assessed by immunofluorescence (IF). A novel rat model crossing flox‐stop DRP1‐GFP rats and VECAD‐Cre expressing rats was generated to assess the vascular and cardiac effects of endothelial‐specific DRP1 overexpression. Endothelial vascular function was determined by endothelial‐dependent flow‐mediated dilation while cardiac function was determined by echocardiography at 20 weeks old and compared to wildtype control group.ResultsData from IF comparing coronary arteries from YC and OC show that OC had higher DRP1 expression compared to YC (1.42 to 1.00, p=0.01). Max dilation measurements, taken at 20‐weeks of age, showed that DRP1‐overexpressing rats was decreased when compared to wildtype (WT) control rats (31.4 to 60.1, p=0.009). Echocardiography revealed that DRP1‐overexpressing rats showed a trend towards a decrease in coronary flow reserve and increased HR in response to a dobutamine stressor when compared to WT. Ejection fraction between the two groups remained largely preserved.ConclusionOur data demonstrate that there may be a critical role for DRP1 within in vitro vasodilation that mimics a CVD pro‐fission phenotype. Future studies will be performed to further evaluate the role of DRP1 in response to other stressors well‐established in age‐dependent CVD such as hypertension.

Endothelium function biomarkers and carotid intima-media thickness changes in relation to NOS3 (rs2070744) and GNB3 (rs5443) genes polymorphism in the essential arterial hypertension.

Objective. The aim of the present study was to clarify the endothelial function biomarkers and carotid "intima media" thickness (IMT) changes in relation to GNB3 (rs5443) and NOS3 (rs2070744) genes polymorphism in the essential arterial hypertension (EAH). Methods. One-hundred EAH patients (48 - control) participated in the case-control study. Soluble vascular cell adhesion molecule (sVCAM-1), total NO metabolites (NO2 -+NO3 -), transcriptional activity of NOS3 gene, endothelium-dependent flow-mediated dilation of the brachial artery (FMD BA), and carotid IMT were studied. GNB3 (rs5443) and NOS3 (rs2070744) genotyping was performed by TaqMan probes (CFX96™Real-Time PCR). Results. The connection of NOS3 (rs2070744) with decreased total NO metabolites (F=71.11; p<0.001), reduced NOS3 genes transcription activity (F=8.71; p<0.001) and increased sVCAM-1 (F=6.96; p=0.002), especially in the C-allele carriers (particularly in CC-genotype patients with lower NO - 16.46% and 40.88%; p<0.001), lowered the transcription activity of NOS3 gene - 46.03% 7 times (p<0.001), and become higher sVCAM-1 - 35.48% and 89.48% (p<0.001), respectively. ANOVA did not confirm the association of GNB3 (rs5443) gene with endothelial function and carotid IMT. Severe EAH was associated with increased carotid IMT - 50.0% (p<0.001) and 57.14% (p=0.007), wider carotid arteries - 17.36% (p=0.012) and 21.79% (p=0.004), and decreased NOS3 genes transcription activity - 34.54% (p=0.003). Atherosclerotic plaques were unilateral - 24.77% (χ2=5.35; p=0.021) or bilateral - 27.62% (χ2=5.79; p=0.016). IMT---gt---0.9 mm was followed by a higher BP (p<0.001), FMD BA 11.80% decrease with compensatory increase in carotid arteries diameters - 17.38% and 21.99% (p<0.001) and sVCAM-1 by 20.49% (p=0.005). Conclusion. NOS3 (rs2070744), but not GNB3 (rs5443), gene associated with the essential arterial hypertension severity relying upon the endothelial function impairment and NOS3 genes reduced transcription activity.

The effect of camelina oil on vascular function in essential hypertensive patients with metabolic syndrome: a randomized, placebo-controlled, double-blind study

The effects of a dietary supplementation with the vegetable ω-3 α-linolenic acid (ALA) on cardiovascular homeostasis are unclear. In this context, it would be interesting to assess the effects of camelina oil. This study aimed to assess the cardiovascular and metabolic effects of camelina oil in hypertensive patients with metabolic syndrome. In a double-blind, placebo-controlled randomized study, treated essential hypertensive patients with metabolic syndrome received, during 6 mo, either cyclodextrin-complexed camelina oil containing≈1.5g ALA/d (n=40) or an isocaloric placebo (n=41), consisting of the same quantity of cyclodextrins and wheat starch. Anthropometric data, plasma lipids, glycemia, insulinemia, creatininemia, TBARs, high-sensitivity C-reactive protein, and n-3, n-6, and n-9 fatty acids in erythrocyte membranes were measured. Peripheral and central blood pressures, arterial stiffness, carotid intima-media thickness, and brachial artery endothelium-dependent flow-mediated dilatation (FMD) and endothelium-independent dilatation were assessed. Compared with placebo, camelina oil increased ALA (mean±SD: 0±0.04 compared with 0.08±0.06%, P<0.001), its elongation product EPA (0±0.5 compared with 0.16±0.65%, P<0.05), and the n-9 gondoic acid (GA; 0±0.04 compared with 0.08±0.04%, P<0.001). No between-group difference was observed for cardiovascular parameters. However, changes in FMD were associated with the magnitude of changes in EPA (r=0.26, P=0.03). Compared with placebo, camelina oil increased fasting glycemia (-0.2±0.6 compared with 0.3±0.5mmol/L, P<0.001) and HOMA-IR index (-0.8±2.5 compared with 0.5±0.9, P<0.01), without affecting plasma lipids, or inflammatory and oxidative stress markers. Changes in HOMA-IR index were correlated with the magnitude of changes in GA (r=0.32, P<0.01). Nutritional intake remained similar between groups. ALA supplementation with camelina oil did not improve vascular function but adversely affected glucose metabolism in hypertensive patients with metabolic syndrome. Whether this adverse effect on insulin sensitivity is related to GA enrichment, remains to be elucidated.