Search Results (151)

Background/Objectives: Gut-derived tryptophan (Trp) metabolites play important roles in metabolic and cardiovascular regulation. Although animal studies suggest their protective effects against metabolic dysfunction, data in adolescents, particularly those with obesity, remain limited. The objective of this study was to evaluate associations between circulating gut-derived Trp metabolites and markers of cardiometabolic, vascular, and platelet health in adolescents with obesity. Methods: Data were analyzed from 28 adolescents (ages 13–18; mean BMI = 36 ± 6.4 kg/m²). Fasting blood was collected to assess lipid profiles using a clinical analyzer and insulin resistance using the homeostatic model assessment for insulin resistance (HOMA-IR). Gut-derived Trp metabolites were measured by UPLC–mass spectrometry, peak oxygen uptake (VO_{2 peak}) by gas exchange during an incremental cycle ergometer test, and body composition by dual-energy X-ray absorptiometry. Platelet spare respiratory capacity (SRC), endothelial function, and liver fat were measured using high-resolution respirometry, flow-mediated dilation (FMD) of the brachial artery, and magnetic resonance imaging respectively. Results: Indole-3-propionic acid was inversely associated with diastolic blood pressure (rho = −0.39, p = 0.047), total cholesterol (rho = −0.55, p = 0.002), and LDL-C (rho = −0.57, p = 0.0014), independent of sex and obesity severity. Indoxyl sulfate was positively correlated with fasting glucose (rho = 0.47, p = 0.012), and adolescents with impaired fasting glucose had 1.6-fold higher IS levels. Indole-3-acetaldehyde declined with age (rho = −0.50, p = 0.007), and Indole-3-acetic acid and indole were higher in Hispanics vs. non-Hispanics. No significant associations were observed between Trp metabolites and FMD, VO₂ peak, or SRC. Conclusions: Gut-derived Trp metabolites, particularly indole-3-propionic and indoxyl sulfate, are associated with markers of cardiometabolic risk in adolescents with obesity. These findings support their potential relevance in early-onset cardiovascular disease risk. Full article

Aging is a major non-modifiable risk factor for cardiovascular disease (CVD), in part due to its detrimental effects on vascular endothelial function. Dietary interventions, including those rich in plant-based components or following dietary patterns such as the Mediterranean Diet, have been shown to improve endothelial function in older adults, assessed via brachial artery flow-mediated dilation (FMD). However, it is well recognized that FMD responses to dietary interventions often show considerable variability among individuals. This variability presents a major challenge to translating findings into effective, population-level guidance highlighting the need for more tailored approaches for CVD risk prevention. Thus, to advance these precision nutrition approaches, research must move beyond the overall group mean effects and begin to investigate the factors driving this variability. This narrative review summarizes current evidence on nutritional interventions that improve endothelial function with aging, highlights potential contributors to individual response variability, and outlines future research directions to reduce this variability to enhance clinical relevance and advance precision nutrition for the aging population. Full article

Women have a lower age-matched cardiovascular risk than men, largely due to estrogen’s protective role in endothelial function. While exercise improves vascular health, acute vascular responses are influenced by factors such as age, fitness level, metabolic status, and exercise modality. In premenopausal women, fluctuations in estrogen levels during the menstrual cycle may further affect vascular reactivity. Here, we review current evidence on acute exercise-induced vascular responses in women, emphasizing menstrual phase influences and key biomarkers such as flow-mediated dilation (FMD), along with others including vascular conductance and pulse wave velocity (PWV). Despite limited and heterogeneous evidence, shear-induced vascular responses, (including FMD) following acute exercise, appear to be relatively stable across menstrual cycle phase, suggesting that strict phasic control may not always be necessary. However, future high-quality studies are needed to further clarify this response. In contrast, other vascular assessments that rely more heavily on neural components—such as vascular conductance and PWV—show greater estrogen sensitivity. Nonetheless, the inconsistencies between studies again underscore the need for future research with hormonal verification. Morever, adequate sample sizes, and standardized exercise protocols will improve both consistency and help develop and promote the inclusion of women in vascular research. Full article

Coronary artery disease (CAD) and peripheral artery disease (PAD) are associated with increased blood viscosity, which contributes to vascular inflammation and impaired microcirculation. Blood viscosity plays a crucial role in disease progression, influencing endothelial function and tissue perfusion. Sarpogrelate hydrochloride, a serotonin receptor antagonist, has antiplatelet and vasodilatory properties that may improve microvascular function and blood rheology. This randomized, parallel-group, open-label, single-center, phase IV clinical trial enrolled 68 patients with both CAD and PAD. The participants were randomized in a 1:1 ratio to receive either aspirin monotherapy (100 mg) or aspirin (100 mg) plus sarpogrelate (300 mg) for 12 weeks. The primary outcome was the change in blood viscosity from baseline to week 12, assessed using the scanning capillary technique. Secondary outcomes included erythrocyte deformability, flow-mediated dilation (FMD), and tissue oxygen delivery index (tODI), which collectively provide insights into microvascular function and oxygen transport efficiency. Elevated blood viscosity is a key factor in cardiovascular disease progression, yet conventional antiplatelet therapy has shown limited effects on hemorheology. Sarpogrelate, by targeting serotonin-mediated pathways, may enhance microcirculatory function and optimize vascular health. These effects could lead to better oxygen delivery and overall vascular health, thereby optimizing cardiovascular outcomes. By integrating hemorheological and vascular markers, this study aims to provide evidence on the potential benefits of combination therapy. Findings could inform optimized antiplatelet strategies to improve vascular health and reduce cardiovascular risk in patients with CAD and PAD. Full article

Background and Objectives: Maternal dyslipidaemia and low-grade inflammation are recognised drivers of in utero vascular remodelling, yet composite dynamic markers that integrate lipid–glycaemic, inflammatory and endothelial signals have not been evaluated. We investigated whether eight-week trajectories in the triglyceride–glucose index (TyG), interleukin-6 (IL-6) and flow-mediated dilation (FMD) outperform single-timepoint lipids for predicting fetal aortic remodelling. Materials and Methods: In a prospective repeated-measures study, 90 singleton pregnancies were examined at 24–26 weeks (Visit-1) and 32–34 weeks (Visit-2). At each visit, we obtained fasting lipids, TyG index, hsCRP, IL-6, oxidative-stress markers (MDA, NOx), brachial flow-mediated dilation (FMD), carotid IMT and uterine-artery Doppler, together with advanced fetal ultrasonography (abdominal-aorta IMT, ventricular strain, Tei-index, fetal pulse-wave velocity). Mothers were grouped by k-means clustering of the visit-to-visit change (Δ) in TG, TyG, hsCRP, IL-6 and FMD into three Metabolic-Inflammatory Response Phenotypes (MIRP-1/2/3). Linear mixed-effects models and extreme-gradient-boosting quantified associations and predictive performance. Results: Mean gestational TG rose from 138.6 ± 14.1 mg/dL to 166.9 ± 15.2 mg/dL, TyG by 0.21 ± 0.07 units and FMD fell by 1.86 ± 0.45%. MIRP-3 (“Metabolic + Inflammatory”; n = 31) showed the largest change (Δ) Δ-hsCRP (+0.69 mg/L) and Δ-FMD (–2.8%) and displayed a fetal IMT increase of +0.17 ± 0.05 mm versus +0.07 ± 0.03 mm in MIRP-1 (p < 0.001). Mixed-effects modelling identified Δ-TyG (β = +0.054 mm per unit), Δ-IL-6 (β = +0.009 mm) and Δ-FMD (β = –0.007 mm per %) as independent determinants of fetal IMT progression. An XGBoost model incorporating these Δ-variables predicted high fetal IMT (≥90th percentile) with AUROC 0.88, outperforming logistic regression (AUROC 0.74). Conclusions: A short-term surge in maternal TyG, IL-6 and endothelial dysfunction delineates a high-risk phenotype that doubles fetal aortic wall thickening and impairs myocardial performance. Composite dynamic indices demonstrated superior predictive value compared with individual lipid markers. Full article

Aortic stenosis (AS) is a progressive valvular heart disease characterized by fibrocalcific remodeling, inflammation, and hemodynamic disturbances. Serum biomarkers may indirectly reflect these processes. Autotaxin (ATX) and lysophosphatidic acid (LPA) have been implicated in osteogenic differentiation of valvular interstitial cells, while growth differentiation factor-15 (GDF-15) reflects cellular stress and vascular changes. Thrombomodulin (TM) indicates endothelial injury and interacts with thrombin. This study aimed to evaluate biomarkers focusing on serum ATX, LPA, GDF-15, and TM levels and flow-mediated dilatation (FMD) in patients with AS. Overall, 149 patients were included in the study: 86 consecutive patients with AS hospitalized due to qualification for invasive treatment of AS and 63 controls. The clinical characteristics, echocardiographic data, FMD, and the following biomarkers—ATX, LPA, GDF-15, and TM—were included in the analysis. AS patients presented increased serum levels of ATX, GDF-15, and TM as compared to the controls. Differences in LPA levels were not statistically significant. FMD values were significantly lower in AS patients. The biomarkers mentioned above and FMD correlated with AS severity. There were no differences in both biomarkers’ serum levels and FMD regarding the hemodynamic AS phenotype. GDF-15 serum level was a risk factor for all-cause mortality and MACCE in the 12-month follow-up. Full article

Background: Endothelial dysfunction and inflammation are associated with the progression of coronary artery disease (CAD) and the pathophysiology of acute coronary syndrome (ACS). We examined the prognostic role of endothelial function and pro-inflammatory cytokines in patients admitted with ACS. Methods: The study population consisted of 864 subjects. From 663 subjects who presented with chest pain, ACS was diagnosed in 460. We additionally recruited 201 consecutive patients with stable CAD. Endothelial function was assessed using flow-mediated dilatation (FMD). Tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) levels were measured via ELISA. Subjects with ACS were followed up for major adverse cardiovascular events (MACE), defined as cardiovascular death, cardiac arrest, myocardial infarction, stroke, nonfatal stroke, other arterial thrombotic events, and hospitalization due to cardiovascular conditions. Results: There was a stepwise impairment in FMD, logTNF-α, and logIL-6 in patients with chest pain of non-epicardial CAD etiology compared to patients with stable CAD and those with ACS (p < 0.001 for all). Moreover, patients who presented with chest pain had increased odds of ACS in accordance with the increasing levels of TNF-α, IL-6, and impaired FMD (p < 0.05 for all). Interestingly, from all these markers, in patients with ACS, we found that only TNF-α levels above 5.19 pg/mL had a 2.5-times-increased risk of MACE compared to patients with TNF-α levels below 5.19 pg/mL, independently of other confounders. Conclusions: In the current study, we found that patients who presented with ACS had impaired endothelial function and increased levels of IL-6 and TNF-α. Full article

Background: Oxidative stress, inflammation, and endothelial dysfunction are important processes in the progression of atherosclerosis and the occurrence of acute coronary syndromes (ACSs). Omega-3 polyunsaturated fatty acids (Omega-3 PUFAs) are present in marine organisms and have the capacity to reduce all these processes and, at the same time, the progression of atherosclerosis and the emergence of ACSs. Aim: To evaluate the role of Omega-3 PUFAs therapy on parameters of oxidative stress, inflammatory syndrome, endothelial dysfunction, and long-term prognosis in acute coronary syndromes. Methods: One thousand one hundred forty patients were admitted to Clinic County Emergency Hospital Brasov with ACS and were enrolled in a prospective study. The study was divided into four groups related to the type of ACS and treatment with Omega-3 PUFAs added to the optimal medical therapy (OMT). The effect of Omega-3 PUFAs therapy associated with the OMT was determined by measuring the dynamics of the following parameters: (a) oxidative stress—total antioxidant status (TAS), oxidated low density lipoprotein cholesterol antibodies (Ab anti-ox-LDL), IgG anti-Myeloperoxidase antibodies (IgG type Ab anti-MPO); (b) inflammatory syndrome—C-reactive protein and fibrinogen; (c) endothelial dysfunction—flow mediated dilation (FMD) and von Willebrand factor (vWf) activity, from baseline to 6 months of follow-up. Clinical events followed at 5 years were cardiovascular and sudden death, Non-ST and ST segment elevation ACS, in stent thrombosis and restenosis, stroke, readmission in hospital for ACS and for heart failure. Results: In ACS groups, treatment with Omega-3 PUFAs added to the OMT significantly decreased the parameters of oxidative stress, inflammatory syndrome, and endothelial dysfunction at 6 months of follow-up. Regarding the clinical events, a significant reduction in the risk of cardiovascular and sudden death and a decreased incidence of Non-ST and ST segment elevation ACS, in-stent restenosis, readmission for ACS and heart failure, was observed in Omega-3 PUFA-treated groups in comparison to control groups. Conclusions: In acute coronary syndromes, therapy with Omega-3 PUFAs added to the OMT resulted in a significant decrease of parameters of oxidative stress, inflammation, and endothelial dysfunction at 6 months and also a significant improvement in the long-term prognosis. Full article

Increasing long-term observations suggest that coronavirus disease 2019 (COVID-19) vasculopathy may persist even 1.5 years after the acute phase, potentially accelerating the development of atherosclerotic cardiovascular diseases. This study systematically reviewed the variability of brachial flow-mediated dilation (FMD) and carotid-femoral pulse wave velocity (cfPWV) from the acute phase of COVID-19 through 16 months of follow-up (F/U). Databases including PubMed, Web of Science, MEDLINE, and Embase were screened for a meta-analysis without language or date restrictions (PROSPERO reference CRD42025642888, last search conducted on 1 February 2025). The quality of the included studies was assessed using the Newcastle–Ottawa Quality Scale. We considered all studies (interventional pre-post studies, prospective observational studies, prospective randomized, and non-randomized trials) that assessed FMD or cfPWV in adults (aged ≥ 18 years) with or after laboratory-confirmed COVID-19 compared with non-COVID-19 controls or that assessed changes in these parameters during the F/U. Twenty-one studies reported differences in FMD, and 18 studies examined cfPWV between COVID-19 patients and control groups during various stages: acute/subacute COVID-19 (≤30 days from disease onset), early (>30–90 days), mid-term (>90–180 days), late (>180–270 days), and very late (>270 days) post-COVID-19 recovery. Six studies assessed variability in FMD, while nine did so for cfPWV during the F/U. Data from 14 FMD studies (627 cases and 694 controls) and 15 cfPWV studies (578 cases and 703 controls) were included in our meta-analysis. FMD showed a significant decrease compared to controls during the acute/subacute phase (standardized mean difference [SMD]= −2.02, p < 0.001), with partial improvements noted from the acute/subacute phase to early recovery (SMD = 0.95, p < 0.001) and from early to mid-term recovery (SMD = 0.92, p = 0.006). Normalization compared to controls was observed in late recovery (SMD = 0.12, p = 0.69). In contrast, cfPWV values, which were higher than controls in the acute/subacute phase (SMD = 1.27, p < 0.001), remained elevated throughout the F/U, with no significant changes except for a decrease from mid-term to very late recovery (SMD= −0.39, p < 0.001). In the very late recovery, cfPWV values remained higher than those of controls (SMD = 0.45, p = 0.010). In the manuscript, we discuss how various factors, including the severity of acute COVID-19, the persistence of long-term COVID-19 syndrome, and the patient’s initial vascular age, depending on metrics age and cardiovascular risk factors, influenced the time and degree of FMD and cfPWV improvement. Full article

Most studies analyzing data from patients who experienced at least one episode of acute COVID-19 infection have attributed the cascade of immediate and late complications to disruption of the inflammatory system and neutrophil activity in particular. Among the various functions of neutrophils is the release of pro-inflammatory mediators, including interleukin-6 (IL-6). Oxidative stress induced by pro-inflammatory mediators secreted by neutrophils leads to vascular endothelial dysfunction. Neutrophil counts and the neutrophil-to-lymphocyte ratio (NLR) are directly associated with COVID-19 patient survival, with higher values correlating with increased mortality. To assess endothelial dysfunction secondary to COVID-19 infection, we conducted a retrospective study involving two patient cohorts, each comprising 99 participants: one group with a history of COVID-19 infection and another without. The study aimed to demonstrate the presence of endothelial dysfunction in patients with moderate COVID-19 infection using flow-mediated dilatation (FMD) of the brachial artery and to evaluate its correlation with key inflammatory markers (erythrocyte sedimentation rate—ESR, fibrinogen, NLR, IL-6). FMD values were significantly reduced (p < 0.0001) in post-COVID-19 patients compared to those without prior infection. ESR (p < 0.0001), fibrinogen (p < 0.0001), C-reactive protein (CRP) (p < 0.0001), leukocyte count (p < 0.0001), and granulocyte count (p < 0.0001) were inversely correlated with FMD values. Among post-COVID-19 patients, all analyzed parameters demonstrated a statistically significant impact on FMD, with ESR showing the strongest effect, accounting for nearly 63% of the dependency. ANOVA testing confirmed an inverse association between NLR quartiles and FMD, as well as between IL-6 levels and FMD. In conclusion, this study highlights the presence of endothelial dysfunction in post-COVID-19 patients, as assessed by FMD, and demonstrates statistically significant inverse correlations between FMD values, IL-6 levels, and the neutrophil-to-lymphocyte ratio. Full article

Vascular endothelial function plays an important role in the pathogenesis of atherosclerosis. The reduction in low-density lipoprotein cholesterol (LDL-C) is a key therapy for preventing coronary artery disease (CAD), but the role of omega-3 fatty acids as residual risk factors of CAD remains controversial. We studied the correlation between serum omega-3 fatty acid levels and endothelial function in patients with CAD receiving statin therapy and examined the effect of eicosapentaenoic acid (EPA) therapy on endothelial function. Methods: A total of 150 consecutive patients with CAD receiving statin therapy (LDL-C levels < 100 mg/dL) were enrolled. Serum omega-3 fatty acid levels were measured, and endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery. Subsequently, 65 patients with impaired FMD (<6%) and low EPA/arachidonic acid (AA) (<0.3) were administered EPA, and FMD was reassessed after 3 months. Results: A multivariate linear regression analysis demonstrated that serum docosahexaenoic acid (DHA) and EPA plus DHA levels were independent determinants of %FMD (β = 0.214 and 0.163, p < 0.05, respectively). The EPA therapy significantly improved %FMD (from 3.7 ± 1.0% to 4.1 ± 1.0%, p < 0.05) in patients with low EPA/AA, and especially in patients with low EPA/AA and high triglyceride levels (from 3.4 ± 1.0% to 4.0 ± 1.1%, p < 0.01). Conclusions: Serum omega-3 fatty acid levels were associated with endothelial dysfunction in patients with CAD receiving statin therapy. EPA therapy improves endothelial function in patients with low EPA/AA, especially those with low EPA/AA and high triglycerides. Full article

Background and Objectives: Endothelial dysfunction (ED) and oxidative stress play major contributions in the initiation and progression of atherosclerosis. Diabetes is a pathological state associated with endothelial damage and enhanced oxidative stress. This study evaluated endothelial dysfunction and oxidative stress in patients with severe coronary artery disease (CAD) undergoing coronary artery bypass graft (CABG) surgery, comparing those with and without type 2 diabetes mellitus (T2DM). Materials and Methods: We included 84 patients with severe coronary artery disease (33 of whom had type 2 diabetes mellitus) who underwent clinical assessments, ultrasound, and coronaryangiography. The SYNTAXI score was calculated from the coronaryangiogram. Blood samples were collected to measure plasma serotonin (5-HT; SER) levels, as well as levels of superoxide dismutase 1(SOD-1) and lectin-like oxidized low-density lipoprotein receptor-1(LOX-1) to assess oxidative stress. Brachial flow-mediated dilation (FMD) was used as a surrogate for endothelial dysfunction (ED),along with serum concentrations of 5-HT. Results: The coronary atherosclerotic burden, assessed using the SYNTAX I score, was more severe in patients with CAD and associated T2DM compared to those with CAD without T2DM (30.5 (17–54) vs. 29 (17–48); p = 0.05). The SYNTAX score was found to be positively correlated with T2DM (p = 0.029; r = 0.238).ED measured by FMD was associated with T2DM (p = 0.042; r = −0.223), with lower FMD measurements in T2DM patients when compared with individuals without this pathology (2.43% (0.95–5.67) vs. 3.46% (1.02–6.75); p = 0.079). Also, in the studied population, T2DM was correlated with serum 5-HT levels (764.78 ± 201 ng/mL vs. 561.06 ± 224 ng/mL; p < 0.001; r = 0.423), with higher plasma circulating levels of 5-HT in patients with T2DM. No statistically significant differences for oxidative stress markers (SOD-1 and LOX-1) were obtained when comparing T2DM and non-T2DM patients with severe CAD. Conclusions: ED (as assessed by brachial FMD and serum 5-HT) is more severe in in diabetic patients with severe CAD scheduled for CABG surgery, while oxidative stress (as evaluated through serum SOD-1 and LOX-1 concentrations) was not influenced by the presence of T2DM in this specific population. The most important finding of the present study is that circulating 5-HT levels are markedly influenced by T2DM. 5-HT receptor-targeted therapy might be of interest in patients undergoing CABG, but further studies are needed to confirm this hypothesis. Full article

Background/Objectives: A pilot study was conducted to investigate the effect of four weeks of creatine monohydrate (CrM) on vascular endothelial function in older adults. Methods: In a double-blind, randomized crossover trial, twelve sedentary, healthy older adults were allocated to either the CrM or placebo (PL) group for four weeks, at a dose of 4 × 5 g/day for 5 days, followed by 1 × 5 g/day for 23 days. Macrovascular function (flow-mediated dilation [FMD%], normalized FMD%, brachial-ankle pulse wave velocity [baPWV], pulse wave analysis [PWA]), microvascular function (microvascular reperfusion rate [% StO₂/sec]), and biomarkers of vascular function (tetrahydrobiopterin [BH₄], malondialdehyde [MDA], oxidized low-density lipoprotein [oxLDL], glucose, lipids) were assessed pre- and post-supplementation with a four-week washout period. Results: CrM significantly increased FMD% (pre-CrM, 7.68 ± 2.25%; post-CrM, 8.9 ± 1.99%; p < 0.005), and normalized FMD% (pre-CrM, 2.57 × 10⁻⁴ ± 1.03 × 10⁻⁴%/AUC_SR; post-CrM, 3.42 × 10⁻⁴ ± 1.69 × 10⁻⁴%/AUC_SR; p < 0.05), compared to PL. Microvascular reperfusion rates increased following CrM (pre-CrM, 2.29 ± 1.42%/sec; post-CrM, 3.71 ± 1.44%/sec; p < 0.05), with no change following PL. A significant reduction in fasting glucose (pre-CrM, 103.64 ± 6.28; post-CrM, 99 ± 4.9 mg/dL; p < 0.05) and triglycerides (pre-CrM, 99.82 ± 35.35; post-CrM, 83.82 ± 37.65 mg/dL; p < 0.05) was observed following CrM. No significant differences were observed for any other outcome. Conclusions: These pilot data indicate that four weeks of CrM supplementation resulted in favorable effects on several indices of vascular function in older adults. Full article

Background: There is compelling evidence of an inverse association between potassium intake and blood pressure (BP). A potential mechanism for this effect may be dietary potassium-mediated augmentation of endothelium-dependent relaxation. To date, studies have investigated potassium intake supplementation over several weeks in healthy volunteers with variable results on vascular function. There is no assessment of the acute vascular effects of potassium supplementation achieved by the ingestion of potassium-rich food in a hypertensive population. Objective: The purpose of this study was to investigate the effect of a high potassium meal on postprandial endothelial function as measured by flow-mediated dilatation (FMD). Methods: We performed an investigator-blinded randomized crossover trial in 33 treated hypertensive individuals. Participants consumed both a high (~2400 mg) and low (~543 mg) K⁺ meal, separated by a one-week washout period. The primary endpoint was endothelial function as assessed by FMD pre-meal and postprandially at 60 and 120 min. Meals were compared at each time point using the Hills–Armitage approach. Results: 33 individuals were included in the study (48% male, mean age 68). In the fasting state (Baseline), and at 60 min postprandial, radial artery FMD was not significantly different between the participants after consumption of either meal (baseline: high K⁺ 4.2 ± 2% versus Low K⁺ 2.6 ± 3%, p = 0.93; 60 min: high K⁺ 3.8 ± 4% versus Low K⁺ 4.1 ± 3%, p = 0.69). However, at 120 min, FMD tended to be higher in participants after the high K⁺ meal (5.2 ± 4.1%) than after the low K⁺ meal (3.9 ± 4.1%) (p = 0.07). There were no differences in participants’ radial artery diameter and blood flow between meals. Conclusions: This study does not support our hypothesis that a single high K⁺ meal improves vascular function in individuals with treated hypertension. This does not contradict the clinical evidence relating greater K⁺ intake with lower BP, but suggests that mechanistic investigations of increased K⁺ intake through diet alone and its impact on endothelial function as a mediator to reducing BP are complex and not simply due to single nutrient-mediated improvement in vascular function. Full article

Endothelial dysfunction (ED) is the in the background of multiple metabolic diseases and a key process in liver disease progression and cirrhosis decompensation. ED affects liver sinusoidal endothelial cells (LSECs) in response to different damaging agents, causing their progressive dedifferentiation, unavoidably associated with an increase in intrahepatic resistance that leads to portal hypertension and hyperdynamic circulation with increased cardiac output and low peripheral artery resistance. These changes are driven by a continuous interplay between different hepatic cell types, invariably leading to increased reactive oxygen species (ROS) formation, increased release of pro-inflammatory cytokines and chemokines, and reduced nitric oxide (NO) bioavailability, with a subsequent loss of proper vascular tone regulation and fibrosis development. ED evaluation is often accomplished by serum markers and the flow-mediated dilation (FMD) measurement of the brachial artery to assess its NO-dependent response to shear stress, which usually decreases in ED. In the context of liver cirrhosis, the ED assessment could help understand the complex hemodynamic changes occurring in the early and late stages of the disease. However, the instauration of a hyperdynamic state and the different NO bioavailability in intrahepatic and systemic circulation—often defined as the NO paradox—must be considered confounding factors during FMD analysis. The primary purpose of this review is to describe the main features of ED and highlight the key findings of the dynamic and intriguing relationship between ED and liver disease. We will also focus on the significance of FMD evaluation in this setting, pointing out its key role as a therapeutic target in the never-ending battle against liver cirrhosis progression. Full article