-
1.
Comparative effects of 2.5mg levamlodipine and 5mg amlodipine on vascular endothelial function and atherosclerosis.
Lu, Y, Yin, J, Wu, X, Fan, Y, Liu, F
Pakistan journal of pharmaceutical sciences. 2019;(5(Special)):2433-2436
Abstract
This study was designed to compare the efficacy of two different racemic antihypertensive drugs on elderly patients with hypertension and their effects on vascular endothelial function and atherosclerosis. A total of 84 elderly hypertensive patients were randomly divided into control and treatment group with 42 patients in each group. The control group was treated with 2.5mg levamlodipine while the treatment group was given 5mg amlodipine. Total effective rate of the treatment group was 90.5%, higher than the control group, that was 71.4% (P<0.05). The time for recovery of related indicators like blood pressure, the total duration of medication were significantly (P<0.05) shorter in the treatment group. Only 1 case of adverse drug reaction was found in the treatment group while 6 cases in control group. Compared to the control group, the treatment group had massive improvement in fingertip pulse volume, flow-mediated dilation of the brachial arteries and endothelin-1 level, carotid intima-media thickness, plaque length & thickness, and blood pressure after the administration. The rate of satisfaction with the in treatment group was 95.3%, higher than that the control group, which was 78.6%. The study concluded that in elderly patients with hypertension, the treatment with 5mg amlodipine enhanced curative effect, fully improved endothelial function & arteriosclerosis and reduced adverse reactions thereby shortening treatment time.
-
2.
Endothelial damage and thromboembolic risk after pulmonary vein isolation using the latest ablation technologies: a comparison of the second-generation cryoballoon vs. contact force-sensing radiofrequency ablation.
Hisazaki, K, Hasegawa, K, Kaseno, K, Miyazaki, S, Amaya, N, Shiomi, Y, Tama, N, Ikeda, H, Fukuoka, Y, Morishita, T, et al
Heart and vessels. 2019;(3):509-516
Abstract
Experimental data suggest that cryoenergy is associated with less endothelial damage and thrombus formation than radiofrequency energy. This study aimed to compare the impact of pulmonary vein isolation (PVI) on the endothelial damage, myocardial damage, inflammatory response, and prothrombotic state between the two latest technologies, second-generation cryoballoon (CB2) and contact force-sensing radiofrequency catheter (CFRF) ablation. Eighty-six paroxysmal atrial fibrillation (AF) patients (55 men; 65 ± 12 years) underwent PVI with either the CB2 (n = 64) or CFRF (n = 22). Markers of the endothelial damage (L-arginine/asymmetric dimethylarginine [ADMA]), myocardial injury (creatine kinase-MB [CK-MB], troponin-T, and troponin-I), inflammatory response (high-sensitive C-reactive protein), and prothrombotic state (D-dimer, soluble fibrin monomer complex, and thrombin-antithrombin complex) were determined before and up to 24-h post-procedure. The total application time was shorter (1,460 ± 287 vs. 2,395 ± 571 [sec], p < 0.01) and total procedure time tended to be shorter (199 ± 37 vs. 218 ± 38 [min], p = 0.06) with CB2 than CFRF ablation. The amount of myocardial injury was greater (CK-MB: 45 ± 17 vs. 11 ± 3 [IU/l], p < 0.01) with CB2 than CFRF ablation. The L-arginine/ADMA ratio was lower (160 ± 51 vs. 194 ± 38, p = 0.028) after CB2 than CFRF ablation. Inflammatory and all prothrombotic markers were significantly elevated post-ablation; however, the magnitude was similar between the two groups. During a mean follow-up of 20 ± 6 months, the single-procedure AF freedom was similar between the CB2 and CFRF groups (60/64 vs. 20/22, p = 0.82). CB2-PVI produces significantly lesser endothelial damage with greater myocardial injury than CFRF-PVI; however, similar anticoagulant regimens are required during the peri-procedural periods in both technologies.
-
3.
Coffee and Endothelial Function: A Coffee Paradox?
Higashi, Y
Nutrients. 2019;(9)
Abstract
Coffee is a popular beverage throughout the world. Coffee contains various chemical compounds (e.g., caffeine, chlorogenic acids, hydroxyhydroquinone, kahweol, cafestol, and complex chemical mixtures). Caffeine is also the most widely consumed pharmacological substance in the world and is included in various beverages (e.g., coffee, tea, soft drinks, and energy drinks), products containing chocolate, and drugs. The effects of coffee and caffeine on cardiovascular diseases remain controversial. It is well known that there are J-curve-type or U-curve-type associations of coffee consumption with cardiovascular events including myocardial infarction and stroke. However, there is little information on the direct and indirect effects of coffee consumption on endothelial function in humans. It is likely that the coffee paradox or caffeine paradox exists the association of coffee intake with cardiovascular diseases, cardiovascular outcomes, and endothelial function. This review focusses on the effects of coffee and caffeine on endothelial function from molecular mechanisms to clinical perspectives.
-
4.
The P2-receptor-mediated Ca2+ signalosome of the human pulmonary endothelium - implications for pulmonary arterial hypertension.
Hennigs, JK, Lüneburg, N, Stage, A, Schmitz, M, Körbelin, J, Harbaum, L, Matuszcak, C, Mienert, J, Bokemeyer, C, Böger, RH, et al
Purinergic signalling. 2019;(3):299-311
-
-
Free full text
-
Abstract
Dysfunction of the pulmonary endothelium is associated with most lung diseases. Extracellular nucleotides modulate a plethora of endothelial functions in the lung such as vessel integrity, vasodilatation, inflammatory, and thrombotic responses as well as survival and DNA repair, mostly via Ca2+ signaling pathways. However, a comprehensive analysis of the molecular components of the underlying P2 receptor-mediated Ca2+ signaling pathways in the lung has not been conducted so far. Therefore, our aim was to identify the principal P2 receptor Ca2+ signalosome in the human pulmonary endothelium and investigate potential dysregulation in pulmonary vascular disease. Comparative transcriptomics and quantitative immunohistochemistry were performed on publicly available RNA sequencing and protein datasets to identify the specific expression profile of the P2-receptor Ca2+ signalosome in the healthy human pulmonary endothelium and endothelial cells (EC) dysfunctional due to loss of or defective bone morphogenetic protein receptor (BMPR2). Functional expression of signalosome components was tested by single cell Ca2+ imaging. Comparative transcriptome analysis of 11 endothelial cell subtypes revealed a specific P2 receptor Ca2+ signalosome signature for the pulmonary endothelium. Pulmonary endothelial expression of the most abundantly expressed Ca2+ toolkit genes CALM1, CALM2, VDAC1, and GNAS was confirmed by immunohistochemistry (IHC). P2RX1, P2RX4, P2RY6, and P2YR11 showed strong lung endothelial staining by IHC, P2X5, and P2Y1 were found to a much lesser extent. Very weak or no signals were detected for all other P2 receptors. Stimulation of human pulmonary artery (HPA) EC by purine nucleotides ATP, ADP, and AMP led to robust intracellular Ca2+ signals mediated through both P2X and P2Y receptors. Pyrimidine UTP and UDP-mediated Ca2+ signals were generated almost exclusively by activation of P2Y receptors. HPAEC made dysfunctional by siRNA-mediated BMPR2 depletion showed downregulation of 18 and upregulation of 19 P2 receptor Ca2+ signalosome genes including PLCD4, which was found to be upregulated in iPSC-EC from BMPR2-mutant patients with pulmonary arterial hypertension. In conclusion, the human pulmonary endothelium expresses a distinct functional subset of the P2 receptor Ca2+ signalosome. Composition of the P2 receptor Ca2+ toolkit in the pulmonary endothelium is susceptible to genetic disturbances likely contributing to an unfavorable pulmonary disease phenotype found in pulmonary arterial hypertension.
-
5.
Predicting Severity of Coronary Artery Disease in Patients With Diabetes Using Endothelial Function Measured With Peripheral Arterial Tonometry: PROCEED Study.
Venuraju, S, Jeevarethinam, A, Mehta, VS, Ruano, S, Dumo, A, Nair, D, Rosenthal, M, Darko, D, Cohen, M, Rakhit, R, et al
Angiology. 2019;(7):613-620
Abstract
Endothelial dysfunction is common in patients with type 2 diabetes mellitus (T2DM) and is associated with atherosclerotic disease. This study aimed to determine prognostic factors for endothelial dysfunction and identify relationships between reactive hyperemia index (RHI) score, clinically relevant coronary artery disease (>50% stenosis), and major adverse cardiovascular events (MACEs) in patients with T2DM. Endothelial function was assessed using peripheral arterial tonometry and correlated with patient characteristics and cardiovascular outcomes during a median follow-up of 22.8 months. Among 235 patients with a median duration of T2DM of 13 years, mean (standard deviation) RHI score was 2.00 (0.76). Serum low- and high-density lipoprotein cholesterol levels positively (P = .004) and negatively (P = .02) predicted RHI score, respectively. Median coronary artery calcium (CAC) score was 109 Agatston units, but no correlation between CAC and RHI scores was observed. The RHI score did not predict the number or severity of coronary plaques identified using computed tomography coronary angiography. Additionally, there was no association between RHI score and the risk of an MACE during follow-up. Overall, endothelial function was not predictive of CAC score, extent, and severity of coronary plaque or MACEs and did not demonstrate utility in cardiovascular risk stratifying patients with T2DM.
-
6.
Statins and antiplatelet agents are associated with changes in the circulatory markers of endothelial dysfunction in chronic kidney disease.
García-Menéndez, E, Marques Vidas, M, Alique, M, Carracedo, J, de Sequera, P, Corchete, E, Pérez García, R, Ramírez Chamond, R, Portolés Pérez, JM
Nefrologia. 2019;(3):287-293
Abstract
BACKGROUNDS AND PURPOSES Patients with chronic kidney disease (CKD) have higher risk of developing cardiovascular disease. In CKD patients the mechanisms involved in, endothelial damage and the role of different drugs used on these patients are not completely understood. The aim of this work is to analyze the effect of statins and platelet antiaggregant (PA) on endothelial microvesicles (EMVs) and other markers of endothelial dysfunction. EXPERIMENTAL APPROACH Cross-sectional study of 41 patients with CKD 3b-4 and 8 healthy volunteers. Circulating levels of EMVs, vascular endothelial growth factor (VEGF), and advance oxidized protein products (AOPPS) were quantified and the correlation with different comorbidity variables and therapeutic strategies were evaluated. RESULTS EMVs are increased in CKD patients as compared with controls (171.1 vs. 68.3/μl, P<.001). It was observed a negative correlation between age and EMVs. Statins and PA were associated with a reduction in EMVs and VEGF levels, independently of the serum total cholesterol levels (TC). The levels of AOPPS and VEGF were not different in CKD vs. controls. CONCLUSION CKD is associated with a change in EMVs, VEGF and AOPP levels. The treatment with statins and PA normalizes these values to almost the observed in controls and this effect is independently of the prevailing TC level. These findings explain the existence of the pleiotropic effects of statins and PA which deserve further studies.
-
7.
Dose-response relationship between cocoa flavanols and human endothelial function: a systematic review and meta-analysis of randomized trials.
Sun, Y, Zimmermann, D, De Castro, CA, Actis-Goretta, L
Food & function. 2019;(10):6322-6330
Abstract
BACKGROUND Several intervention studies have investigated the relationship between cocoa flavanols and endothelial function. However, the shape of the association and the type of compounds responsible for the effects are largely unknown. OBJECTIVE To examine the dose-response association between the consumption of cocoa flavanols and endothelial function, measured by flow-mediated dilation (FMD). DESIGN Two investigators searched Scopus® for the relevant human intervention studies, which were pooled and meta-analysed. Heterogeneity in the findings was explored with various subgroup analyses. RESULTS Fifteen published articles with 18 intervention arms met the inclusion criteria. Participants in these intervention groups received 80 to 1248 mg (mean: 704 mg) more flavanols than control groups. A significant improvement of FMD by 1.17% (95% CI: 0.76% to 1.57%) was calculated, with strong evidence of a non-linear association (inverted U-shape) between cocoa flavanols and FMD. CONCLUSIONS This meta-analysis provides evidence that cocoa flavanols could significantly improve endothelial function, with an optimal effect observed with 710 mg total flavanols, 95 mg (-)-epicatechin or 25 mg (+)-catechin. However, there was substantial variation in the results that could not be explained by the characteristics that we explored, and there were significant risk-of-bias concerns with a large majority of the studies.
-
8.
The Effects of Choline and Magnesium Co-Supplementation on Metabolic Parameters, Inflammation, and Endothelial Dysfunction in Patients With Type 2 Diabetes Mellitus: A Randomized, Double-Blind, Placebo-Controlled Trial.
Rashvand, S, Mobasseri, M, Tarighat-Esfanjani, A
Journal of the American College of Nutrition. 2019;(8):714-721
Abstract
Objective: To our knowledge, no study has investigated the effects of choline and magnesium co-supplementation on metabolic parameters, inflammation, and endothelial dysfunction in patients with type 2 diabetes mellitus (T2DM). The aim of this study was investigation of the effects of the choline and magnesium co-supplementation on metabolic parameters, inflammation, and endothelial dysfunction in patients with T2DM.Methods: A randomized double-blind placebo-controlled parallel clinical trial was carried out among 96 diabetic patients. Ninety-six patients were randomly assigned to either choline, magnesium, choline-magnesium, or placebo for 2 months. Anthropometric measurement; metabolic, inflammatory, and endothelial markers; dietary intake; and physical activity were assessed at baseline and after treatment.Results: There was a significant change in serum magnesium in both magnesium and choline-magnesium groups (p < 0.05). Also, significant changes were observed in interleukin (IL)-6 levels in magnesium and choline-magnesium groups (p < 0.05). Moreover, vascular cell adhesion molecule-1 (VCAM-1) levels decreased in choline and choline-magnesium groups (p < 0.05). When adjusted for potential confounders, inflammation and endothelial factors (IL-6 and VCAM-1) decreased significantly in the choline-magnesium group as compared to other groups (p < 0.05). Compared to baseline values there were no significant differences in all anthropometric measurements and metabolic factors among four groups (p > 0.05).Conclusions: Choline and magnesium co-supplementation was more effective in improving inflammation and endothelial dysfunction than supplementation with choline or magnesium alone.
-
9.
Effects of a short-term interval aerobic training program with recovery bouts on vascular function in sedentary aged 70 or over: A randomized controlled trial.
Bouaziz, W, Lang, PO, Schmitt, E, Leprêtre, PM, Lefebvre, F, Momas, C, Kaltenbach, G, Geny, B, Vogel, T
Archives of gerontology and geriatrics. 2019;:217-225
Abstract
BACKGROUND Interval aerobic training programs with active recovery bouts (IATP-R) are reported as being more adapted to seniors while improving cardiorespiratory and endurance parameters. Report of benefits on vascular function is still limited. PURPOSE To measure the impact of IATP-R on vascular function among seniors. METHODS Sedentary volunteers (≥70 years of age) were randomly assigned to either IATP-R (n = 30) or control group (n = 30). The IATP-R consisted of 2 weekly sessions of 30-min (6 × 4-min at first ventilatory threshold (VT1) intensity + 1-min at 40% of VT1) cycling exercise over 9.5-week. Controls remained their sedentary life over the same period. In all participants, the endothelial function was measured by flow-mediated dilation (FMD) in brachial artery and arterial stiffness through the carotid/radial and carotid/femoral pulse wave velocity (PWV). Systolic (SBP) and diastolic blood pressure (DBP) were measured at baseline and 9.5 weeks later. RESULTS Resulting from a planned interim analysis, IATP-R improved SBP (IATP-R: from 133.7 ± 9.8 to 122.6 ± 9.4 mmHg vs. Controls: from 128.9 ± 12.5 to 132.6 ± 14.7 mmHg), DBP (IATP-R: from 80.2 ± 7.0 to 74.1 ± 6.7 mmHg vs. Controls: from 77.1 ± 6.8 to 80.3 ± 7.5 mmHg), and FMD (IATP-R: from 6.7 ± 2.0 to 7.5 ± 2.7% vs. Controls: from 7.9 ± 2.7 to 7.5 ± 2.5%). No significant impact on PWV was measured. CONCLUSION Although these findings resulted from an interim analysis, IATP-R might be effective in regulating BP and improving endothelial function among sedentary seniors.
-
10.
Effect of acute exercise on postprandial endothelial function in postmenopausal women: a randomized cross-over study.
Shah, M, Bailey, S, Gloeckner, A, Kreutzer, A, Adams-Huet, B, Cheek, D, Mitchell, J
Journal of investigative medicine : the official publication of the American Federation for Clinical Research. 2019;(6):964-970
Abstract
High-sugar intake may cause endothelial dysfunction. It is unknown if a bout of aerobic exercise improves endothelial dysfunction caused by a high-sugar meal in postmenopausal women. This study evaluated if prior aerobic exercise attenuates postprandial endothelial dysfunction in postmenopausal women. Twenty-two postmenopausal women (age [mean±SD]: 60.4±6.5 years; % body fat: 40.3%±7.5%) underwent an exercise (EX) or no exercise (NE) condition, in a random order, 13-16 hours prior to the high-sugar meal consumption. The EX condition included a 60 min bout of supervised aerobic exercise at 75% of age-predicted maximum heart rate. The high-sugar meal, consumed after a 12-hour fast, contained 33% of the subjects' daily energy needs, and 75.6% energy from carbohydrates. Flow-mediated dilation (FMD) and blood concentrations of glucose, insulin, endothelin-1 (ET-1), and nitric oxide (NO) were assessed at baseline and 60 min, 120 min, and 180 min postprandially. Repeated measures analysis test showed that there were no condition by time interaction or condition effects for FMD, glucose, insulin, or NO. There was a significant condition by time interaction but no condition effect for ET-1. Area under the curve was also not different by condition for insulin sensitivity or the above variables. In conclusion, prior aerobic exercise compared with NE did not affect FMD, blood glucose, insulin, ET-1 or NO concentrations, or insulin sensitivity following a high-sugar meal in postmenopausal women. Future studies should look at the effect of different EX intensities on meal-induced endothelial dysfunction in this population. Trial Registration: ClinicalTrials.gov Identifier: NCT02919488.