Markers Of Endothelial Function Research Articles

A low testosterone level impairs erectile function by increasing endocan expression in rat penile corpus cavernosum.

The mechanism by which a state of low testosterone leads to erectile dysfunction (ED) has not been determined. Endocan is a novel marker of endothelial function. However, whether endocan is involved in the regulation of erectile function under low testosterone levels remains unclear. In this study we sought to determine whether a low-testosterone state inhibits erectile function by regulating endocan expression in the endothelial cells of the rat penile corpus cavernosum. Thirty-six male Sprague-Dawley rats aged 8 weeks were randomly assigned to 6 groups (n = 6 per group) as follows: (1) control, (2) castration, (3) castration + testosterone treatment (treated with 3mg/kg testosterone propionate per 2days), (4) control + transfection (4weeks after castration, injected with lentiviral vector (1 × 108 transduction units/mL, 10μL), (5) castration + transfection, or (6) castration + empty transfection. One week after the injection, we measured the maximal intracavernous pressure/mean arterial pressure (ICPmax/MAP), serum testosterone and nitric oxide (NO) levels, and the expression of endocan, phospho-endothelial NO synthase (p-eNOS), eNOS, phospho-protein kinase B (p-AKT), and AKT in the rat penile corpus cavernosum. Under a low-androgen state, the expression of endocan in the rat penile corpus cavernosum was significantly increased, which inhibited the AKT/eNOS/NO signaling pathway and resulted in ED. In the castration group, the expression of endocan in the rat penile corpus cavernosum was significantly higher than that in the control group (P < .05). Additionally, the levels of p-AKT/AKT, p-eNOS/eNOS, and NO in the rat penile corpus cavernosum and ICPmax/MAP were significantly lower in the castration group than in the control group (P < .05). In the castration + transfection group compared with the castration group there was a significant decrease in the expression of endocan (P < .05) and an increase in the ratios of p-AKT/AKT, p-eNOS/eNOS, and ICPmax/MAP (P < .05) in the rat penile corpus cavernosum. Downregulating the expression of endocan in the penile corpus cavernosum may be a feasible approach for treating ED caused by hypoandrogenism. The results of this study indicte that endocan may affect NO levels and erectile function through multiple signaling pathways, but further experiments are needed to clarify the relationship between endocan and androgens. A low-testosterone state inhibits the AKT/eNOS/NO signaling pathway by increasing the expression of endocan in the rat penile corpus cavernosum and impairing erectile function in rats. Decreasing the expression of endocan in the penile corpus cavernosum can improve erectile function in rats with low testosterone levels.

Effects of Anthocyanins on Cognition and Vascular Function: A Systematic Review.

Good vascular function is crucial for cerebral blood flow and cognitive performance. Diets high in anthocyanins have been shown to improve vascular function and are associated with improvements in cognition. This systematic review investigates randomized controlled trials examining the impact of anthocyanin intake on both cognition and vascular function. Of the 1486 studies identified through searching Ovid Medline and AMED, PsychInfo, Web of Science, and Scopus, 20 studies are selected which measured cognitive and vascular function. Overall, positive effects on verbal and working memory are observed, which are supported by studies using functional magnetic resonance imagingto demonstrate increased blood flow in brain regions related to these cognitive domains. However, effects of anthocyanins on blood pressure and markers of endothelial function are inconsistent. This systematic review provides evidence for a positive effect of anthocyanins on cognition and insight into the relevance of endothelial function. Anthocyanins are widely available and can be easily consumed in a range of different fruits, vegetables, and other products. Further studies should establish the optimal daily intake of anthocyanins for cardiovascular and cognitive health.

Effect of omega-3 fatty acid supplementation on markers of inflammation and endothelial function in patients with chronic heart disease: A systematic review and meta-analysis.

Chronic heart disease (CHD) is still a major global cause of morbidity and mortality, necessitating effective therapeutic interventions to mitigate its progression. Omega-3 fatty acids (FAs) have garnered attention for their potential anti-inflammatory and endothelial-protective properties in CHD management. The present study aims to assess the efficacy of Omega-3 FA supplementation on markers of inflammation and endothelial function in patients with CHD. To achieve this, we used the relevant keywords to search international databases (Web of Science, PubMed, Embase, and Scopus) and extract publications evaluating the effectiveness of omega-3 FA supplementation on inflammation markers and endothelial function in patients with CHD. STATA (version 15) and the random and fixed-effects models were used to evaluate the collected data. Thirteen clinical trial studies met inclusion criteria, with a total sample size of 853 individuals (406 cases and 447 controls). The cases had a mean age of 58 ± 10.3 years. The pooled results indicated that omega-3 Omega-3 FA supplementation significantly reduced the level of circulating IL-6 (SMD = -0.47, 95% CI -1.29 to 0.35, %, p < 0.001), hs-CRP (SMD = -0.21, 95% CI -0.70 to 0.28, p = 0.01), and TNF-α (SMD = -0.56, 95% CI -1.14 to 0.01, p < 0.001) in patients with CHD. Also, findings revealed that a daily supplement of omega-3 significantly increased FMD by 0.34% (95% CI: 0.14-0.54%, p < 0.001) as compared with placebo by a fixed-effect model in patients with CHD. These findings underscore the potential therapeutic utility of omega-3 fatty acid supplementation in modulating inflammation and endothelial dysfunction in patients with CHD.

The effects of HIV-1-proteins and antiretroviral therapy on aortic endothelial cells (AECs). A mechanistic in vitro approach

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Research Foundation Introduction Endothelial dysfunction (ED) is an early precursor of cardiovascular disease characterized by decreased nitric oxide (NO) and increased oxidative stress, creating a pro-inflammatory environment. Increased ED and cardiovascular risk have been observed in HIV-1 infection and antiretroviral therapy (ART). Purpose The United Nations AIDS update indicates that in 2015 17.0 million people worldwide were living with HIV and receiving antiretroviral therapy. Considering the extent of this global pandemic and its comorbidity with CVD, zooming in on HIV’s intersection with antiretroviral therapy and cardiovascular health is of paramount importance. Yet, many of the mechanisms involved are still poorly understood. This knowledge can ultimately assist with the careful selection of antiretroviral-agents in patients with underlying cardiovascular risk factors. Objectives Establishing a simulated model of in vitro HIV-1-infection in aortic endothelial cells and determining the effects of non/nucleoside reverse transcriptase inhibitors (NRTI/NNRTIs) and protease inhibitors (PIs) on markers of endothelial function and the expression/activation of vascular signalling proteins. Methods A simulated HIV-1-model was established by adding recombinant HIV-1 proteins to growth medium in a single cocktail containing Tat, Gp160 and Nef. ART1 (NRTI/NNRTIs) were administered as a single cocktail to growth medium, containing efavirenz (EFV), emtricitabine (FTC) and tenofovir (TDF). ART2 (PIs) were administered as a single cocktail to growth medium, containing lopinavir (LPV) and ritonavir (RTV). All the aforementioned treatments were subject to dose-response investigations and treatment lasted 24 hours. Cell viability, NO-production and oxidative stress were measured using fluorescent probes. Selected dosages from above studies were further used and important vascular signalling proteins in HIV-1 exposed AECs were investigated by western blotting. Results HIV-1 (100ng/ml, 24h) resulted in ↓NO-levels (DAF-fluorescence intensity: 100±1.25% vs. 76.00±3.67%; p&amp;lt;0.05) with no oxidative stress. HIV-1+PI treatment lowered NO levels (DAF-fluorescence: 100±0.72% vs. 94.47±1.91%; p&amp;lt;0.05). HIV-1+ NRTI/NNRTI treatment had no effects. HIV-1+PI treatment ↓IκBα expression (inhibitory signalling protein in pro-inflammatory NF-κB pathway) (1.0 ± 0.15 vs 0.37 ± 0.03; p&amp;lt;0.05) and ↓eNOS expression (1.0 ± 0.21 vs. 0.28 ± 0.04; p&amp;lt;0.05). The same was observed for PKB/Akt (1.0 ± 0.03 vs. 0.68 ± 0.02; p&amp;lt;0.05). No effects on cell viability and oxidative stress were observed. Conclusion Exposure of AECs to combined HIV-1-protein and PI treatment lowered NO-production, which may be linked to underlying PKB/Akt and eNOS downregulation. HIV-1+PI treatment was associated with increased pro-inflammatory NF-κB signalling. Overall, our results suggest that a dysfunctional state was induced in AECs exposed to HIV-1 proteins and PI treatment.

The Relationship of Mitral Annular Calcification and Aortic Valve Sclerosis to Endothelial Dysfunction.

Calcific aortic valve disease (CAVD) and mitral annular calcification (MAC) are associated with various cardiovascular diseases and may influence systemic vascular pathologies. However, their relationship with endothelial dysfunction and carotid intima-media thickness (CIMT) remains poorly elucidated. This research aims to explore the associations between MAC, aortic valve sclerosis (AVS), and markers of vascular dysfunction, specifically CIMT and endothelial function. This prospective observational study included 200 patients undergoing routine echocardiographic evaluation at the National Heart Institute between May 2022 and April 2023. Patients were stratified into four groups namely isolated MAC (38 patients), isolated AVS (72 patients), combined MAC and AVS (50 patients), and a control group without MAC or AVS (40 patients). All participants underwent comprehensive cardiovascular evaluation, including transthoracic echocardiography (TTE) and carotid duplex ultrasonography. Endothelial function was determined by measuring reactive hyperemia-induced alterations in brachial artery diameter. The mean age of participants was 60.6±8.4 years, with a predominance of male subjects (64%). No significant differences were noted in baseline demographic and clinical characteristics across the groups. Patients with isolated AVS, isolated MAC, and both conditions demonstrated increased CIMT compared to controls, with significant differences noted in the combined MAC and AVS group compared to controls (p-value=0.031). Endothelial dysfunction was observed in 14.8% of the AVS group and 21.1% in the combined group, but no significant differences existed when compared to controls. The study also revealed that patients with AVS are more likely to exhibit increased CIMT (p-value=0.008). Both MAC and AVS are connected to increased CIMT, suggesting a link with systemic atherosclerotic processes. Although the existence of endothelial dysfunction was not significantly higher in patients with valvular calcifications, the findings support the need for further research into the cardiovascular implications of CAVD and MAC.

Assessing Stress Induced by Fluid Shifts and Reduced Cerebral Clearance during Robotic-Assisted Laparoscopic Radical Prostatectomy under Trendelenburg Positioning (UroTreND Study).

In addition to general anesthesia and mechanical ventilation, robotic-assisted laparoscopic radical prostatectomy (RALP) necessitates maintaining a capnoperitoneum and placing the patient in a pronounced downward tilt (Trendelenburg position). While the effects of the resulting fluid shift on the cardiovascular system seem to be modest and well tolerated, the effects on the brain and the blood-brain barrier have not been thoroughly investigated. Previous studies indicated that select patients showed an increase in the optic nerve sheath diameter (ONSD), detected by ultrasound during RALP, which suggests an elevation in intracranial pressure. We hypothesize that the intraoperative fluid shift results in endothelial dysfunction and reduced cerebral clearance, potentially leading to transient neuronal damage. This prospective, monocentric, non-randomized, controlled clinical trial will compare RALP to conventional open radical prostatectomy (control group) in a total of 50 subjects. The primary endpoint will be the perioperative concentration of neurofilament light chain (NfL) in blood using single-molecule array (SiMoA) as a measure for neuronal damage. As secondary endpoints, various other markers for endothelial function, inflammation, and neuronal damage as well as the ONSD will be assessed. Perioperative stress will be evaluated by questionnaires and stress hormone levels in saliva samples. Furthermore, the subjects will participate in functional tests to evaluate neurocognitive function. Each subject will be followed up until discharge. Conclusion: This trial aims to expand current knowledge as well as to develop strategies for improved monitoring and higher safety of patients undergoing RALP. The trial was registered with the German Clinical Trials Register DRKS00031041 on 11 January 2023.

Soluble urokinase plasminogen activator receptor (suPAR) in children with obesity or type 1 diabetes as a marker of endothelial dysfunction: a cross-sectional study.

Pediatric obesity and type 1 diabetes mellitus (T1DM) represent two common chronic diseases associated with chronic inflammation, endothelial dysfunction and long-term complications. The aim of the present study was to assess the possible diagnostic and prognostic value of soluble urokinase plasminogen activator receptor (suPAR), a marker of inflammation and impaired endothelial function, in children with the diseases.In this cross-sectional study, children and adolescents with T1DM (N = 41) or obesity (N = 37), aged < 18 years old, and without proteinuria were included, together with children of similar age and without evident morbidity that served as controls (N = 42). Serum samples were obtained during standard outpatient follow up and the urokinase-type plasminogen activator receptor (suPAR) concentrations were measured using a commercially available sandwich ELISA kit (DUP00, R&D systems). Clinical and biochemical indices that were also assessed include body mass index (BMI) z-score, Tanner stages, glycosylated haemoglobin (HbA1c), fasting lipid profile and serum creatinine. Mean serum suPAR levels were significantly higher in patients with obesity compared to patients with T1DM and controls, while children with T1DM had similar suPAR levels to controls. Also, serum suPAR levels showed a negative correlation with age (Spearman rho -0.359, p < 0.001) and serum creatinine levels (Spearman rho -0.334, p = 0.005), and a positive correlation with BMI z-score (Spearman rho 0.354, p = 0.009) in the whole cohort. Conclusion: Serum suPAR may be a useful predictive marker of inflammation or endothelial dysfunction for children with obesity and T1DM, as well as a promising therapeutic target. Further studies are needed in order to clarify whether the reported differences in suPAR levels could reflect a greater impairment of the inflammation status and endothelial function in children with obesity compared to children with T1DM. What is Known: • Paediatric obesity and type 1 diabetes are characterised by chronic inflammation and metabolic dysregulation. • Urokinase plasminogen activator receptor (uPAR) has been proposed as a useful biomarker for chronic inflammation and cardiovascular risk in adults. What is New: • Serum suPAR levels were increased in children and adolescents with obesity compared to those with T1DM and healthy controls; thus, obesity may affect the inflammatory status and endothelial function to a higher degree than T1DM during childhood. • Serum suPAR may serve as a diagnostic and predictive marker of inflammation and endothelial dysfunction for children and adolescents with obesity and T1DM.

Association between Ambient Particulate Air Pollution and Soluble Biomarkers of Endothelial Function: A Meta-Analysis.

The burden of cardiovascular diseases caused by ambient particulate air pollution is universal. An increasing number of studies have investigated the potential effects of exposure to particulate air pollution on endothelial function, which is one of the important mechanisms for the onset and development of cardiovascular disease. However, no previous study has conducted a summary analysis of the potential effects of particulate air pollution on endothelial function. To summarize the evidence for the potential effects of short-term exposure to ambient particulate air pollution on endothelial function based on existing studies. A systematic literature search on the relationship between ambient particulate air pollution and biomarkers of endothelial function including endothelin-1 (ET-1), E-selectin, intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) was conducted in PubMed, Scopus, EMBASE, and Web of Science up to 20 May 2023. Subsequently, a meta-analysis was conducted using a random effects model. A total of 18 studies were included in this meta-analysis. A 10 μg/m3 increase in short-term exposure to ambient PM2.5 was associated with a 1.55% (95% CI: 0.89%, 2.22%) increase in ICAM-1 and a 1.97% (95% CI: 0.86%, 3.08%) increase in VCAM-1. The associations of ET-1 (0.22%, 95% CI: -4.94%, 5.65%) and E-selectin (3.21%, 95% CI: -0.90% 7.49%) with short-term exposure to ambient PM2.5 were statistically insignificant. Short-term exposure to ambient PM2.5 pollution may significantly increase the levels of typical markers of endothelial function, including ICAM-1 and VCAM-1, suggesting potential endothelial dysfunction following ambient air pollution exposure.

Effect of walnut consumption on markers of endothelial function in adults: A systematic review and meta-analysis of randomized controlled trials.

Findings on the effect of walnut consumption on endothelial function are conflicting. Therefore, the present systematic review and meta-analysis summarized available trials in this regard. A systematic search was performed in online databases including PubMed-Medline, Scopus, and ISI Web of Science up to October 2023. Articles that reported the effect of walnut intake on flow-mediated dilation (FMD), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and stimulus-adjusted response measure (SARM) were included. Random effects models for a weighted mean difference (WMD) or standardized mean difference (SMD) were used to test for the overall effect. Six eligible trials were analyzed (250 participants). Walnut intake significantly increased FMD (WMD: 0.94%, 95% CI: 0.12 to 1.75; p = 0.02). However, meta-analysis could not show any beneficial effect of walnut intake on ICAM-1 (SMD: -0.23, 95% CI: -0.68 to 0.22; p = 0.31), VCAM-1 (SMD: -0.02, 95% CI: -1.38 to 1.34; p = 0.97), and SARM (WMD: 0.01%, 95% CI: -0.01 to 0.04; p = 0.28). In conclusion, the present meta-analysis suggests that walnuts may reduce cardiovascular disease risk by improving FMD. However, further studies should be performed on adults to determine the effect of walnut intake on endothelial function.

Effect of Yoga-Based Cardiac Rehabilitation Program on Endothelial Function, Oxidative Stress, and Inflammatory Markers in Acute Myocardial Infarction: A Randomized Controlled Trial.

The aim of this study was to evaluate the effects of yoga-based cardiac rehabilitation (Yoga-CaRe) on the endothelial system, oxidative stress, and inflammatory markers in patients with acute myocardial infarction (MI). A sub-study was conducted in two clinical sites of the Yoga-CaRe trial (a multicenter randomized controlled trial). Participants with acute MI were randomized and allocated to either the Yoga-CaRe program (13 sessions with encouragement to home practice) or enhanced standard care (three educational sessions). Endothelial function, oxidative stress, and inflammatory biomarkers were assessed using biomarkers such as asymmetric dimethylarginine (ADMA), endothelial nitric oxide synthase (eNOS), endothelin-1 (ET-1), E-selectin, P-selectin, vascular cell adhesion molecule (VCAM), intercellular cell-adhesion molecule-1, total nitric oxide concentration (NOx), oxidized low-density lipoprotein (Oxd-LDL), superoxide dismutase, total antioxidant capacity (TAOC), tumor necrosis factor-alpha (TNFα), and C-reactive protein (CRP) at baseline and 12 weeks. Laboratory and statistical analysis were done by staff blinded to group allocation. Eighty-two patients (of the 110 patients recruited) completed the study. The mean age was 53.1 ± 10.6 and 51.9 ± 10.7 years in enhanced standard care and Yoga-CaRe group, respectively. At 12 weeks, Yoga-CaRe significantly reduced ADMA, ET-1, and ICMA-1 than the enhanced standard care group. Although E-selectin and VCAM at 12 weeks were reduced in both groups, enhanced standard care had a significantly higher reduction than the Yoga-CaRe group. Among markers of oxidative stress, TAOC increased in the Yoga-CaRe group. We found no difference in eNOS, NOx, P-selectin, TNFα, CRP, and Oxd-LDL between the two groups. Yoga-CaRe improved the endothelial function (through a reduction in ET-1 and modulating adhesion molecules) and enhanced antioxidant capacity.

Associations between Aging and Vitamin D Status with Whole-Body Nitric Oxide Production and Markers of Endothelial Function

BackgroundAging and vitamin D deficiency have been associated with reduced nitric oxide (NO) synthesis and impaired endothelial function (EF) but the evidence in humans remains weak. ObjectivesTwo independent cross-sectional studies were designed to evaluate the association between age, sex, and plasma vitamin D concentrations with physiological and biochemical biomarkers of NO synthesis and EF in young and older healthy participants (Study 1) and in overweight and obese postmenopausal females (Study 2). MethodsIn Study 1, 40 young (20–49 y) and older (50–75 y) males and females (10 participants per age and sex group) were included. Resting blood pressure and ear-to-finger peripheral pulse wave velocity (PWV) were measured. A stable-isotopic method was used to determine whole-body NO production. Plasma 25-hydroxyvitamin D (25(OH)D), nitrate, nitrite, and asymmetric dimethylarginine (ADMA) concentrations were determined. In Study 2, 80 older overweight and obese females (age 61.2 ± 6.2 y, body mass index 29.5 ± 4.4 kg/m2) were recruited. Postocclusion reactive hyperemia (PORH) and peripheral PWV were measured. Plasma concentrations of 25(OH)D, nitrate, cyclic guanosine monophosphate, 3-nitrotyrosine (3-NT), endothelin-1, vascular endothelial growth factor, and ADMA were determined. ResultsIn Study 1, whole-body NO production was significantly greater in young compared with older participants (0.61 ± 0.30 μmol·h−1·kg−1 compared with 0.39 ± 0.10 μmol·h−1·kg−1, P = 0.01) but there was no evidence of a sex difference (P = 0.81). Plasma 25(OH)D concentration was not associated with PWV (r = 0.18, P = 0.28) or whole-body NO production (r = −0.20, P = 0.22). Plasma ADMA concentration was associated positively with age (r = 0.35, P = 0.03) and negatively with whole-body NO production (r = −0.33, P = 0.04). In Study 2, age was associated with lower PORH (r = −0.28, P = 0.02) and greater ADMA concentrations (r = 0.22, P = 0.04). Plasma 25(OH)D concentration was inversely associated with 3-NT concentrations (r = −0.31, P = 0.004). ConclusionsOlder age was associated with lower whole-body NO production. Plasma vitamin D concentrations were not associated with NO production or markers of EF but showed a weak, significant correlation with oxidative stress in postmenopausal overweight females.

High School and Beyond: Cohort Data for Studying the Effects of Education on Midlife Cognition

AbstractBackgroundThe objective of our presentation is to describe the utility of data from the High School and Beyond (HSB) cohort for studying the impact of early life circumstances and experiences—especially related to education—on risk of midlife cognitive impairment. HSB is a cohort study of a large (n∼25,500), diverse, nationally‐representative probability sample of American high school students in 1980. Participants were surveyed in 1980, 1982, 1984, 1986, 1992, and 2014/2015 with high rates of response; teachers and school administrators were also surveyed, and transcripts provide information about secondary and postsecondary course taking. HSB data from 1980 through 1992 include detailed information about educational contexts, opportunities, and outcomes as well as about family circumstances, labor force activities, and other early life factors.MethodA 2021/2022 follow‐up survey with surviving cohort members featured lengthy interviews; a home health visit that included blood and saliva collection and anthropometric measures; and linkages to administrative records (e.g., mortality records, prescription records). Interviews included immediate and delayed recall tasks; a phonemic fluency task; a semantic fluency task; working memory tasks; self‐reported memory complaints; and detailed information about health conditions.ResultOf the ∼24,330 surviving HSB panelists, ∼13,900 completed surveys in 2021/2022. Of the ∼13,900 sample members completing surveys, ∼4,880 completed a home health visit; an additional ∼1,560 mailed back saliva kits. HSB ultimately received ∼4,430 blood samples by the time fieldwork concluded in late 2022. Blood collected in 2022 is being used to construct (1) measures that define the main pathological features of ADRD (e.g., Aβ42, Aβ40, p‐tau 181, total tau, NFL, and gFAP); (2) measures that reflect cognition‐relevant pathologies (e.g., hemoglobin A1c, inflammatory markers, markers of endothelial function, markers of blood‐brain barrier disfunction, and blood lead levels); and (3) measures of biological aging (e.g., the GrimAge clock, DunedinPACE pace of aging, the Hannum clock).ConclusionHSB is now an extraordinary resource for studying—using a large, diverse national sample—the effects of educational contexts, opportunities, and outcomes on midlife cognitive functioning and biological markers of ADRD risk.

Improvement of endothelial function parameters during cardiac rehabilitation predicts cardiovascular death and heart failure hospitalization in patients with HFpEF: 3 years follow up

Abstract Purpose To evaluate the effects of cardiac rehabilitation on Dipeptidyl peptidase 4 (DPP4), circulating Insulin-like growth factor binding protein 1 (IGF BP1) levels and circulating blood marker of endothelial function, nitric oxide (NOx) and to assess their prognostic significance on composite endpoint cardiovascular death (CVD) and heart failure (HF) hospitalization. Methods 88 patients (pts) (62,3±5,7 years) with HFpEF who were admitted at residential rehabilitation center were enrolled in the study. All pts underwent a supervised 3 weeks exercise training. At baseline and after 3 weeks values of DPP4, IGF BP1 and NOx were determined and exercise test was performed. Clinical long-term follow-up (3 years) was performed. All medical therapy was documented, and for this analysis, we focused on CVD death and HF hospitalization. Results After follow-up period, 34 (38,6%) patients experienced composite endpoint (CE group: 11 CVD and 23 HF hospitalization), while 54 (61,4%) pts did not report any deterioration in health status (non-CE group). Baseline values of DPP4, IGF BP1 and NOx did not differ between the examined groups. After 3 weeks of exercise training DPP4 decreased significantly in both group (CE group, from 782,14±124,76 to 642,17±110,53 μg/L, p&amp;lt;0,001; non-CE group, from 774,12±98,65 to 554,71±88,12 μg/L, p&amp;lt;0,001); also IGF BP1 (CE group, from 904,77±115,34 to 689,14±96,55 ng/mL, p&amp;lt;0,001; non-CE group from 898,17±108,55 to 558,18±88,62 ng/mL, p&amp;lt;0,001); and NOx increased (CE group, from 35,4±6,5 to 41,4±5,2 µmol/L, p&amp;lt;0,001; non-CE group, from 36,1±5,2 to 47,2±4,7 µmol/L, p&amp;lt;0,001). All second values od DPP4, IGF BP1 and NOx differ significantly between the examined groups (p&amp;lt;0,001 for all). Exercise capacity (METs) has increased significantly in both groups, but second value in CE group was significantly lower than in non-CE group (P&amp;lt;0.001). A positive correlation was found between IGF BP1 decrease and NOx increase (r=0.554, P&amp;lt;0.01), between IGF BP1 decrease and DPP 4 decrease (r=0.685, P&amp;lt;0.01), between IGF BP1 decrease and METs increase (r=0.653, P&amp;lt;0.01), between DPP4 decrease and NOx increase (r=0.775, P&amp;lt;0.001), between DPP 4 decrease and METs increase (r=0.708, P&amp;lt;0.01), and between METs increase and NOx increase (r=0.746, P&amp;lt;0.001). After adjusment for age and gender, univaried COX-regression analyses showed that NOx increase (OR 0.832, CI 0.462-0.994, p&amp;lt;0.01), DPP4 decrease (OR 0.718, CI 0.614–0.926, p=0.01), IGF BP1 decrease (OR 0.952, CI 0.889–0.999, p=0.002) and METS increase (OR 0.921, CI 0.774-0.977, p=0.014) significantly predict composite endpoint (CV death and HF hospitalization). Conclusion Residential CV rehabilitation, in patients with HFpEF, improved endothelial function. Pts with higher increase of NOx and METs, and greater reduction in DPP4 and IGF BP1 after 3 weeks of specialized cardiac rehabilitation, during 3 years follow up, were at lower risk of CV death and HF hospitalization.

Abstract 18949: Bariatric Surgery is Associated With Improved Coronary Microvascular Function and Cardiorespiratory Fitness in Patients With Ischemia and Non-Obstructive Coronary Arteries (INOCA)

Introduction - Severe obesity is associated with cardiometabolic disease and coronary microvascular dysfunction, as reflected by impaired coronary flow reserve (CFR). Bariatric surgery promotes sustained weight loss and lower incidence of diabetic microvascular complications, but its effect on the coronary microcirculation is unclear. In this ongoing pilot study, we aimed to investigate the impact of bariatric surgery on CFR, endothelial function, and cardiorespiratory fitness in patients with severe obesity and INOCA. Methods - Consecutive patients (N=19) with severe obesity (BMI≥35 kg/m 2 ), exertional dyspnea and planned bariatric surgery were enrolled. Patients underwent cardiac stress positron emission tomography (PET), peripheral arterial tonometry (PAT), echocardiogram and cardiopulmonary exercise testing (CPET) at baseline and after a median of 6.2 months post-surgery (N=9 completed to date). CFR was quantified as stress/rest myocardial blood flow (MBF) from PET. Reactive hyperemia index (RHI), a marker of endothelial function, was calculated as the ratio between PAT signal post and pre-occlusion in the corresponding arm. Results - Median age was 50 (Q1-Q3 42-54) years and 63% were female. At baseline, median BMI was 43 (40-54), LVEF was 0.62, and %LV visual ischemia was 0. Higher BMI inversely correlated with CFR (r= -0.53, p=0.02). As compared to baseline, patients post-surgery (78% sleeve gastrectomy, 22% gastric bypass) had significantly decreased BMI (45.2 vs. 34.3, p=0.008) and improved stress MBF [1.8 (1.3-2.2) vs. 2.4 (1.8-2.8), p&lt;0.02], CFR [2.3 (1.9-2.6) vs. 3.1 (2.4-3.6), p&lt;0.02] and peripheral endothelial function [RHI 1.5 (1.4-1.8) vs. 2.4 (1.8-2.8) vs. p=0.04]. These changes were accompanied on CPET by significantly higher exercise workload [112 (84.2-146) vs. 124.5 (90.5-149) W, p=0.046] and relative peak VO 2 [12.5 (11.9-14) vs. 15.2 (12.6-17) mL/kg/min, p=0.028]. Higher stress MBF directly correlated with relative peak VO 2 (r=0.53, p=0.04). Conclusion - In this pilot clinical study, bariatric surgery was associated with significant improvements in coronary microvascular function, peripheral endothelial function, and cardiorespiratory fitness in symptomatic patients with severe obesity after six months.

Effect of purified Shilajit (Asphaltum punjabianum) on oxidative stress, arterial stiffness and endothelial function in elderly with hypertension: A randomised controlled study

Objectives: Growing evidence showed involvement of vascular oxidative stress in the development of endothelial dysfunction, arterial stiffness and hypertension. Many clinical trials of antioxidants have proven unsuccessful in prevention of atherosclerosis and cardiovascular events. There is a need of new therapies that reduce age- and hypertension associated arterial stiffness in elderly individuals. We aimed to determine if shilajit (Asphaltum punjabianum), a natural phytocomplex which is immunomodulator, anti-inflammatory, antioxidant and antiaging, can reduce oxidative stress and improve arterial function in the elderly with hypertension. Materials and Methods: A parallel arm, open-label randomised controlled study was conducted on 60 elderly patients with hypertension. Study-group participants received shilajit (500 mg-twice/day for 30 days) with antihypertensives while control-group participants received only antihypertensive therapy. Oxidative stress, arterial stiffness and endothelial function markers were assessed at baseline and after 30 days of treatment. Results: Between-group analysis showed a significant decrease in oxidative stress markers: Malondialdehyde (P &lt; 0.001) and oxidised-low-density lipoproteins (P = 0.015); and increase in total antioxidant capacity (P = 0.002), superoxide dismutase (P &lt; 0.001) and reduced glutathione (P &lt; 0.001) with complementary therapy of shilajit. There was no change in the markers of arterial stiffness and endothelial function. Conclusion: These findings suggest that shilajit may be of value as a natural antioxidant to reduce oxidative stress in elderly hypertension patients.

Early Human Pathophysiological Responses to Exertional Hypobaric Decompression Stress.

INTRODUCTION: Consistent blood biomarkers of hypobaric (altitude) decompression stress remain elusive. Recent laboratory investigation of decompression sickness risk at 25,000 ft (7620 m) enabled evaluation of early pathophysiological responses to exertional decompression stress.METHODS: In this study, 15 healthy men, aged 20-50 yr, undertook 2 consecutive (same-day) ascents to 25,000 ft (7620 m) for 60 and 90 min, breathing 100% oxygen, each following 1 h of prior denitrogenation. Venous blood was sampled at baseline (T0), immediately after the second ascent (T8), and next morning (T24). Analyses encompassed whole blood hematology, endothelial microparticles, and soluble markers of cytokine response, endothelial function, inflammation, coagulopathy, oxidative stress, and brain insult, plus cortisol and creatine kinase.RESULTS: Acute hematological effects on neutrophils (mean 72% increase), eosinophils (40% decrease), monocytes (37% increase), and platelets (7% increase) normalized by T24. Consistent elevation (mean five-fold) of the cytokine interleukin-6 (IL-6) at T8 was proinflammatory and associated with venous gas emboli (microbubble) load. Levels of C-reactive protein and complement peptide C5a were persistently elevated at T24, the former by 100% over baseline. Additionally, glial fibrillary acidic protein, a sensitive marker of traumatic brain injury, increased by a mean 10% at T24.CONCLUSIONS: This complex composite environmental stress, comprising the triad of hyperoxia, decompression, and moderate exertion at altitude, provoked pathophysiological changes consistent with an IL-6 cytokine-mediated inflammatory response. Multiple persistent biomarker disturbances at T24 imply incomplete recovery the day after exposure. The elevation of glial fibrillary acidic protein similarly implies incomplete resolution following recent neurological insult.Connolly DM, Madden LA, Edwards VC, D'Oyly TJ, Harridge SDR, Smith TG, Lee VM. Early human pathophysiological responses to exertional hypobaric decompression stress. Aerosp Med Hum Perform. 2023; 94(10):738-749.

The Role of Endothelinergic and Nitroxidergic Reactions in Predicting the Functional Outcome in Patients with Ischemic Stroke of Different Severity

The aim of this study was to assess the value of nitric oxide (NO) and endothelin-1 (ET-1) serum concentrations as potential biomarkers for predicting the functional outcome in patients with acute ischemic stroke. Material and methods. A total of 37 patients diagnosed with ischemic stroke and admitted to a multidisciplinary vascular center were included in the study. The patients were divided into two groups based on the severity of neurological deficits as determined by the National Institutes of Health Stroke Scale (NIHSS): Group 1 consisted of 20 patients with NIHSS scores 15, and Group 2 consisted of 17 patients with NIHSS scores 15. The functional outcome was assessed using the NIHSS absolute values and the degree of disability measured by the Modified Rankin Scale (mRS) by comparing the values before and after baseline treatment. Lab evaluation included quantitative assessment of stable NO and ET-1 metabolites in patient’s serum at admission and on day 10 of hospital stay. The SPSS Statistics V23.0 for Windows software package, Python programming language, and Pandas and SciPy libraries were used for statistical data processing. Results. Group 1 patients demonstrated a statistically significant decrease in NIHSS (P=0.0013) and mRS (P0.0001) scores, which was indicative of a favorable functional outcome. Group 2 patients showed some recovery of only neurological deficit measured by NIHSS scale (P=0.0012), changes in degree of disability by mRS were statistically insignificant. On Day10 of hospital stay, both groups showed a clinically significant increase in ET-1 content, and slight change in NO concentration. NIHSS score demonstrated a significant negative correlation with baseline ET-1 concentrations: R=–0.82, P=0.00023 — in Group 1; R=–0.55, P=0.00075 — in Group 2. Modified RS scores showed negative correlation with NO (R=–0.50, P=0.00044) and ET-1 (R=–1.0, P=0.0074) concentrations in Group 1, and positive correlation with NO (R=0.55, P=0.0023) and ET-1 (R=0.33, P=0.04) concentrations in Group 2. Conclusion. Monitoring of NO and ET-1 serum concentrations provides valuable insights for personalized assessment of the anticipated functional outcome in patients with cerebral ischemia. Further research and the development of prognostic mathematical models are needed to validate the use of endothelial function markers as predictive indicators of patients' recovery potential during the acute phase of ischemic stroke.

The Effect of Folic Acid Supplementation on Endothelial Function and Arterial Stiffness Markers in Adults: A Systematic Review and Meta-Analysis.

Folic acid might improve endothelial function, but the results are inconclusive. This systematic review evaluated the effect of folic acid supplementation on endothelial parameters and arterial stiffness in adults. The study protocol was registered with the PROSPERO database (CRD42021290195). The PubMed, Web of Sciences, Cochrane and Scopus databases were searched to identify English-language randomised controlled trials of the effect of folate supplementation on arterial stiffness and endothelial function markers in adults. There were significant differences between the effect of folic acid and placebo on flow-mediated dilation (random-effects model, standardized mean differences (SMD): 0.888, 95% confidence interval (CI): 0.447, 1.329, p < 0.001) and monocyte chemotactic protein 1 (random-effects model, SMD: -1.364, 95% CI: -2.164, -0.563, p < 0.001), but there was no significant difference in the central pulse wave velocity (fixed-effects model, SMD: -0.069, 95% CI: -0.264, 0.125, p = 0.485) and peripheral pulse wave velocity (fixed-effects model, SMD: -0.093, 95% CI: -0.263, 0.077, p = 0.284). In conclusion, folic acid might have a favourable effect on endothelial function but may not affect arterial stiffness. Further studies are needed to confirm these results.

The Association between 4-Tertiary-Octylphenol, Apoptotic Microparticles, and Carotid Intima-Media Thickness in a Young Taiwanese Population.

As one of the most common alkylphenols, 4-tertiary-octylphenol (4-tOP) is commonly used in many consumer products. Our previous epidemiological study revealed a negative correlation between serum 4-tOP levels and carotid intima-media thickness (CIMT), which serves as a biomarker of arteriosclerosis. We aimed to explore the role of apoptotic microparticles, markers of vascular endothelial cell function, in the 4-tOP and CIMT connection. To investigate this, we enrolled 886 Taiwanese adolescents and young adults (aged 12-30 years) and examined the relationships among serum 4-tOP levels, apoptotic microparticles (CD31+/CD42a-, CD31+/CD42a+), and CIMT. Our results showed negative associations among serum 4-tOP levels, both apoptotic microparticles, and CIMT in multiple linear regression analysis. The odds ratios for CIMT (≥75th percentile) and the natural logarithm of 4-tOP were highest when both CD31+/CD42a- and CD31+/CD42a+ were greater than the 50th percentile. Conversely, the odds ratios were lowest when both CD31+/CD42a- and CD31+/CD42a+ were less than the 50th percentile. In the structural equation model, we demonstrated that serum 4-tOP levels were negatively correlated with CIMT and indirectly and negatively correlated with CIMT through both apoptotic microparticles. In conclusion, our study reported the inverse association between 4-tOP apoptotic microparticles and CIMT in a young Taiwanese population. Further experimental studies are needed to clarify these associations.

Circulating Soluble EPCR Levels Are Reduced in Patients with Ischemic Peripheral Artery Disease and Associated with Markers of Endothelial and Vascular Function.

(1) Background: Endothelial dysfunction initiates cardiovascular pathologies, including peripheral artery disease (PAD). The pathophysiology of impaired new vessel formation in the presence of angiogenic stimuli, such as ischemia and inflammation, is unknown. We have recently shown in mice that reduced endothelial protein C receptor (EPCR) expression results in defective angiogenesis following experimental hindlimb ischemia. (2) Purpose: To determine soluble (s)EPCR levels in the plasma of patients with PAD and to compare them with the protein C activity and biomarkers of endothelial function, inflammation, and angiogenesis. (3) Methods and Results: Clinical tests of vascular function and immunoassays of plasma from patients with PAD stage II were compared to age- and sex-matched individuals with and without cardiovascular risk factors or PAD stage III/IV patients. sEPCR levels were significantly lower in PAD stage II patients compared to subjects with risk factors, but no PAD, and further decreased in PAD stage III/IV patients. Plasma protein C activity or levels of ADAM17, a mediator of EPCR shedding, did not differ. Significant associations between sEPCR and the ankle-brachial index (p = 0.0359), age (p = 0.0488), body mass index (p = 0.0110), and plasma sE-selectin levels (p = 0.0327) were observed. High-sensitive CRP levels and white blood cell counts were significantly elevated in PAD patients and associated with serum glucose levels, but not sEPCR. In contrast, plasma TNFα or IL1β levels did not differ. Circulating levels of VEGF were significantly elevated in PAD stage II patients (p = 0.0198), but not associated with molecular (sE-selectin) or functional (ankle-brachial index) markers of vascular health. (4) Conclusions: Our findings suggest that circulating sEPCR levels may be useful as biomarkers of endothelial dysfunction, including angiogenesis, in persons older than 35 years and that progressive loss of endothelial protein C receptors might be involved in the development and progression of PAD.