Systemic Endothelial Function Research Articles

Impaired systemic microvascular function in patients with resistant arterial hypertension and microalbuminuria: an observational study

Abstract Background Systemic arterial hypertension (SAH) is one of the most prevalent diseases worldwide and is known to be associated with alterations of microvascular function. It is well known that microalbuminuria (MAU) is considered an early marker of renal and cardiac injury in SAH and is an independent risk factor for cardiovascular events in this population. Additionally, it is associated with altered endothelial function, which occurs from the early stages and can be considered an early marker. In some cases, SAH presents as resistant arterial hypertension (RAH), resulting in a worse prognosis compared to individuals with non-resistant hypertension. Moreover, MAU is associated with higher mortality, independent of glomerular filtration rate. Endothelial dysfunction is also a risk marker found in different conditions and can add to MAU in patients with RAH. Purpose To investigate systemic microvascular function in patients with RAH, with or without MAU. Methods 64 patients with RAH, of both genders (50% men), were evaluated, with 32 having MAU and 32 without MAU (defined as a urinary albumin/creatinine ratio between 30 and 300 mg/g in a routine urine sample). Microvascular function assessment was performed using a laser speckle system, allowing analysis of cutaneous microvascular flow. Flow measurements were expressed in arbitrary perfusion units (APU) divided by the mean arterial pressure to obtain cutaneous vascular conductance (CVC). A post-occlusive reactive hyperemia (PORH) test was performed, with brachial artery occlusion using a sphygmomanometer 50 mmHg above systolic pressure for 3 minutes; cutaneous flow was measured after release of the occlusion. Results Patients with or without MAU did not differ in terms of age, frequency of diabetes, and chronic kidney disease. The peak CVC values during PORH were 0.64 ± 0.15 and 0.55 ± 0.15 APU/mmHg in RH and RH + MAU patients, respectively (P=0.03). The delta values (peak – baseline) during PORH were 0.31 ± 0.11 and 0.25 ± 0.09 APU/mmHg in RH and RH + MAU patients, respectively (P=0.04)(Figure 1). Conclusions PORH-induced vasodilation was found to be reduced in patients with RAH and MAU compared to patients without MAU. This finding shows alteration of endothelium-dependent vasodilation mechanisms in these patients, indicating reduced systemic microvascular endothelial function. Endothelial dysfunction may be associated with glomerular permeability changes, contributing to MAU and further increasing the risk for these patients. This suggests the need for more intensive therapeutic interventions and better risk stratification for these patients, as endothelial dysfunction can be found in the early stages of the disease.Figure 1

Reduced systemic microvascular function in patients with resistant hypertension and microalbuminuria: an observational study.

Resistant hypertension (RH) may be associated with microalbuminuria (MAU), a marker of cardiovascular risk and target organ damage, and both may be related to microvascular damage. Laser speckle contrast imaging (LSCI) is an innovative approach for noninvasively evaluating systemic microvascular endothelial function useful in the context of RH with or without MAU. Microalbuminuria was defined as a urine albumin-to-creatinine ratio between 30 and 300 mg/g. Microvascular reactivity was evaluated using LSCI to perform noninvasive measurements of cutaneous microvascular perfusion changes. Pharmacological (acetylcholine [ACh], or sodium nitroprusside [SNP]) and physiological (postocclusive reactive hyperemia [PORH]) stimuli were used to evaluate vasodilatory responses. Thirty-two patients with RH and a normal urine albumin-to-creatinine ratio (RH group) and 32 patients with RH and microalbuminuria (RH + MAU) were evaluated. Compared with patients without MAU, patients with RH + MAU showed reduced endothelial-dependent systemic microvascular reactivity, as demonstrated by an attenuation of microvascular vasodilation induced by PORH. On the other hand, ACh-induced vasodilation did not differ between groups. The results also revealed reduced endothelial-independent (SNP-induced) microvascular reactivity in hypertensive patients with MAU compared with patients without MAU. In this study, there was evidence of endothelial dysfunction associated with impaired microvascular smooth muscle function in patients with RH + MAU. This may suggest that patients with RH need more intensive therapeutic strategies for the control of blood pressure to avoid further vascular damage and the resulting consequences.The study was registered at ClinicalTrials.gov ( https://register.clinicaltrials.gov ) under protocol # NCT05464849, initial release 12/07/2022.

Diagnostic accuracy of serum biomarkers to identify giant cell arteritis in patients with polymyalgia rheumatica

IntroductionPolymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are frequently overlapping conditions. Unlike in GCA, vascular inflammation is absent in PMR. Therefore, serum biomarkers reflecting vascular remodelling could be used...

Aortic Valve Stenosis Causes Accumulation of Extracellular Hemoglobin and Systemic Endothelial Dysfunction.

Whether aortic valve stenosis (AS) can adversely affect systemic endothelial function independently of standard modifiable cardiovascular risk factors is unknown. We therefore investigated endothelial and cardiac function in an experimental model of AS mice devoid of standard modifiable cardiovascular risk factors and human cohorts with AS scheduled for transcatheter aortic valve replacement. Endothelial function was determined by flow-mediated dilation using ultrasound. Extracellular hemoglobin (eHb) concentrations and nitric oxide (NO) consumption were determined in blood plasma of mice and humans by ELISA and chemiluminescence. This was complemented by measurements of aortic blood flow using 4-dimensional flow acquisition by magnetic resonance imaging and computational fluid dynamics simulations. The effects of plasma and red blood cell (RBC) suspensions on vascular function were determined in transfer experiments in a murine vasorelaxation bioassay system. In mice, the induction of AS caused systemic endothelial dysfunction. In the presence of normal systolic left ventricular function and mild hypertrophy, the increase in the transvalvular gradient was associated with elevated eryptosis, increased eHb, and increased plasma NO consumption; eHb sequestration by haptoglobin restored endothelial function. Because the aortic valve orifice area in patients with AS decreased, postvalvular mechanical stress in the central ascending aorta increased. This was associated with elevated eHb, circulating RBC-derived microvesicles, eryptotic cells, lower haptoglobin levels without clinically relevant anemia, and consecutive endothelial dysfunction. Transfer experiments demonstrated that reduction of eHb by treatment with haptoglobin or elimination of fluid dynamic stress by transcatheter aortic valve replacement restored endothelial function. In patients with AS and subclinical RBC fragmentation, the remaining circulating RBCs before and after transcatheter aortic valve replacement exhibited intact membrane function, deformability, and resistance to osmotic and hypoxic stress. AS increases postvalvular swirling blood flow in the central ascending aorta, triggering RBC fragmentation with the accumulation of hemoglobin in the plasma. This increases NO consumption in blood, thereby limiting vascular NO bioavailability. Thus, AS itself promotes systemic endothelial dysfunction independent of other established risk factors. Transcatheter aortic valve replacement is capable of limiting NO scavenging and rescuing endothelial function by realigning postvalvular blood flow to near physiological patterns. URL: https://www.clinicaltrials.gov; Unique identifiers: NCT05603520 and NCT01805739.

Enhanced External Counterpulsation for Management of Postacute Sequelae of SARS-CoV-2 Associated Microvascular Angina and Fatigue: An Interventional Pilot Study.

Postacute sequelae of SARS-CoV-2 infection (PASC) are a novel clinical syndrome characterized in part by endothelial dysfunction. Enhanced external counterpulsation (EECP) produces pulsatile shear stress, which has been associated with improvements in systemic endothelial function. To explore the effects of EECP on symptom burden, physical capacity, mental health, and health-related quality of life (HRQoL) in patients with PASC-associated angina and microvascular dysfunction (MVD). An interventional pilot study was performed, including 10 patients (male = 5, mean age 50.3 years) recruited from a tertiary specialized PASC clinic. Patients with angina and MVD, defined as index of microcirculatory resistance (IMR) ≥25 and/or diagnosed through stress perfusion cardiac magnetic resonance imaging, were included. Patients underwent one modified EECP course (15 one-hour sessions over five weeks). Symptom burden, six-minute walk test, and validated generic self-reported instruments for measuring psychological distress and HRQoL were assessed before and one month after treatment. At baseline, most commonly reported PASC symptoms were angina (100%), fatigue (80%), and dyspnea (80%). Other symptoms included palpitations (50%), concentration impairment (50%), muscle pain (30%), and brain fog (30%). Mean IMR was 63.6. After EECP, 6MWD increased (mean 29.5 m, median 21 m) and angina and fatigue improved. Mean depression scores showed reduced symptoms (-0.8). Mean HRQoL scores improved in seven out of eight subscales (+0.2 to 10.5). Patients with PASC-associated angina and evidence of MVD experienced subjective and objective benefits from EECP. The treatment was well-tolerated. These findings warrant controlled studies in a larger cohort.

Combined pathogenetic therapy of erectile dysfunction

Introduction. Erectile dysfunction (ED) is a common condition that reduces the quality of life of numerous men. Therefore, optimising treatment protocols is always a challenge.Objective. To evaluate the efficacy of "Edelim®" for pathogenetic therapy for erectile dysfunction.Materials and methods. The study included 67 men (40 – 65 years old) with ED. The patients were divided into two treatment groups: the main group received tadalafil 5 mg PO o.d. + “Edelim®”, the control group received tadalafil 5 mg PO o.d. only. As effectiveness criteria anthropometric studies were used, IIEF-5 scale, metabolic profile blood tests, and systemic endothelial function was assessed.Results. Over 12 months of therapy, the IIEF-5 score increased by 28.2% in the main group and by 10.3% in the control group. After 12 months in the main group total cholesterol, LDL, triglycerides decreased by 14.8%, 10.7% and 13.9% respectively. The reactive hyperaemia index after 3, 6 and 12 months increased by 6.6%, 10.9% and 22.0%, respectively. In the control group these indices did not change significantly. The main group showed a stable decrease in body mass and waist circumference by an average of 2.6% and 3.8% respectively after 12 months. In the control group, body mass did not change significantly.Conclusion. Some patients require combination therapy to address metabolic risk factors and disorders, despite the high efficacy of PDE-5 inhibitors in improving erection quality. “Edelim®” is the first product created specifically for long-term combined pathogenetic therapy of ED with metabolic disorders.

Vascular Risks, Aging, and Late-Onset Dementia: Overlapping Etiologies Point to 'Scavenger Receptor'-Mediated Therapeutics

Early changes in systemic vascular stiffness and endothelial function can contribute to altered cerebrovascular hemodynamics and impaired cognitive function; additionally, these vascular changes point to potential targets for prevention and treatment strategies in people with mild cognitive impairment. Although the pathogenic mechanisms underlying these vascular changes are heterogeneous and complex, one common feature is the development of cerebral blood flow (CBF) dysregulation, resulting in chronic cerebral hypoperfusion (CCH) and subsequently an insufficient blood supply to the brain. However, the incorporation of drugs, or other bioactive molecules, into specifically a "high density lipoprotein-like" ("HDL-like") lipid nanocarrier can result in the production of a multitasking "combination therapeutic" – capable of targeting cell-surface scavenger receptors (mainly SR-BI). Such targeting behavior of this proposed (biomimetic-nanocarrier) therapeutic vehicle can facilitate the nanocarrier's enhanced endocytosis into various target cells which, in turn, increases the likelihood that this multitasking "combination therapeutic" provides some enhanced efficacy at different stages of dementia.

Systemic Inflammation, Endothelial Function, and Risk of Periodontitis in Overweight/Obese Adults.

The network interaction between systemic inflammatory mediators, endothelial cell adhesion function, and adiponectin as mediators of the association between metabolic diseases and periodontitis has not been evaluated. The objective of this study is to assess whether the interaction of baseline serum levels of TNF-α, hs-CRP, ICAM-1, VCAM-1, and adiponectin leads to periodontitis. Five hundred and ninety-seven overweight/obese (overweight: BMI 25 to <30 kg/m2; obese: >30 kg/m2) adults, aged 40-65 years, with complete 3-year follow-up data were included. Generalized structural equation models with negative binomial regression were used to estimate the regression coefficient (β) for the outcome number of teeth with probing pocket depth (PPD) ≥ 4 mm and bleeding on probing (BOP) at 3-year follow-up for a 1 standard deviation unit increase (Δ = +1SD) in each biomarker. After adjusting for multiple covariates, baseline ICAM-1 and VCAM-1 had significant direct effects on increased log-transformed number of teeth with PPD ≥ 4 mm and BOP (β: 0.16; 95% CI: 0.02-0.30; β: 0.15; 95% CI: 0.02-0.30, respectively). Baseline hs-CRP showed a significant indirect effect via ICAM-1 on the log-transformed number of teeth with PPD ≥ 4 mm and BOP (β: 4.84; 95% CI: 0.27-9.42). Thus, elevated serum ICAM-1 and VCAM-1 have a significant direct effect and increased hs-CRP has a significant indirect effect on the predicted level of periodontitis at the 3-year follow-up among overweight/obese Hispanic adults.

A prospective study on varicose veins surgery impact on systemic endothelial function evaluated by arterial brachial flow mediated dilation.

Chronic venous disease (CVD) is a prevalent pathology, and endothelial dysfunction is recognized as a core of its physiopathology. Flow-mediated dilation (FMD) is one of the most widely used tests for evaluating endothelial function. The aim of this study is to evaluate the influence of varicose vein (VV) surgery on FMD. A prospective study with patients with superficial CVD and saphenous incompetence on Doppler ultrasonography that were proposed for VV surgery. The FMD test was performed before and 6months after the procedure. The operator performing the post-operative evaluation was blinded to the pre-operative result. A total of 42 patients were included in the analysis. The median pre-operative percent change of FMD was 4.20% (±1.30) and the post-operative was 4.56% (±1.25) (p = 0.819). Our findings do not corroborate the presence of an overall endothelial dysfunction prone to modulation by surgery. Nevertheless, further studies are needed to confirm our findings.

Interrelation between the parameters of endogenous vascular regulation, oxidative stress and the markers of inflammatory response in COVID-19 patients while on extracorporeal membrane oxygenation

Introduction. Extracorporeal membrane oxygenation has found wide application in clinical practice during the COVID-19 pandemic. Oxidative stress, endothelial dysfunction, and systemic inflammatory response syndrome play an important role in the pathogenesis of COVID-19. Our research was designed to study correlations in-between those factors and the impact of extracorporeal membrane oxygenation on them.Aim. The study of systemic inflammatory response and endothelial function in patients with COVID-19 during extracorporeal membrane oxygenation.Material and methods. In the course of a prospective study, we examined 100 COVID-19 patients aged 26 to 75 years, median 55 years [47;60], who were treated at the N.V. Sklifosovsky Research Institute for Emergency Medicine, using extracorporeal membrane oxygenation. As a control group (normal), 25 practically healthy people whose median age was 32 years [25;39] were examined. The function of the vascular endothelium was assessed by the content of nitric oxide stable metabolites in the blood serum and the level of angiotensin-converting enzyme. Next, the ratio of nitric oxide metabolite to angiotensin-converting enzyme level was calculated, reflecting the imbalance between endotheliumdependent vasodilation and vasoconstriction. To assess the severity of oxidative stress in blood serum, malondialdehyde was determined as a marker of lipid peroxidation. The state of the antioxidant system was assessed in terms of total antioxidant status of blood serum. The presence of an imbalance in the system of lipid peroxidation and the antioxidant system total antioxidant status was judged by the oxidative stress coefficient, i.e. the ratio of malondialdehyde to the total antioxidant activity.Results. The analysis showed the presence and progression of endothelial dysfunction, impaired vascular regulation, activation of free radical processes, the presence of an imbalance in the prooxidant/antioxidant system, as well as the progression of the inflammatory process with a decrease in the level of markers of the COVID-19 severity.Conclusion. Further studies of the correlation between endothelial damage and the severity of the systemic inflammatory response syndrome may be of fundamental importance for explaining the pathophysiological mechanisms of COVID-19 course and developing new treatments for such patients.

Effect of Carotid Body Denervation on Systemic Endothelial Function in a Diabetic Animal Model.

Endothelial dysfunction is an essential intermediary for development of cardiovascular diseases associated with diabetes and hypertension (HT). The carotid body (CB) dysfunction contributes to dysmetabolic states, and the resection of carotid sinus nerve (CSN) prevents and reverts dysmetabolism and HT. Herein, we investigated if CSN denervation ameliorates systemic endothelial dysfunction in an animal model of type 2 diabetes mellitus (T2DM).We used Wistar male rats submitted to HFHSu diet during 25weeks and the correspondent age-matched controls fed with a standard diet. CSN resection was performed in half of the groups after 14weeks of diet. In vivo insulin sensitivity, glucose tolerance and blood pressure, ex vivo aortic artery contraction and relaxation and nitric oxide (NO) levels in plasma and aorta, aorta nitric oxide synthase (NOS) isoforms, and PGF2αR levels were evaluated.We demonstrated that, alongside to dysmetabolism and HT reversion, CSN resection restores endothelial function in the aorta and decreases the NO levels in plasma and aorta at the same time that restores normal levels of iNOS in aorta without changing eNOS or PGF2αR levels.These results suggest that the modulation of CB activity can be important for the treatment of HT and endothelial dysfunction related with T2DM.

Long-term assessment of systemic microcirculatory function and plasma cytokines after coronavirus disease 2019 (COVID-19)

Systemic microvascular dysfunction has been shown to be present in COVID-19, and serum cytokines are known to be involved in the regulation of vascular function. We sought to evaluate systemic microvascular endothelial function, with laser doppler perfusion monitoring (LDPM), and plasma levels of cytokines after acute COVID-19. Individuals admitted to a Cardiology hospital with acute COVID-19 and followed for 12–15 months after recovery underwent noninvasive evaluation of systemic endothelium-dependent microvascular reactivity by cutaneous LDPM with local thermal hyperemia (LTH). A multiplex biometric immunoassay panel was used to assess 48 serum cytokines and chemokines. Twenty patients and 14 control volunteers were enrolled. The areas under the curves of vasodilation induced by LTH were significantly increased after recovery (P=0.009) and were not different from values obtained in healthy volunteers (P = 0.85). The peak microvascular flow during LTH did also significantly increase (P = 0.02), and was not different form values obtained in healthy volunteers (P = 0.55). Several cytokines displayed significantly reduced serum concentrations after recovery from COVID-19. In conclusion, endothelium-dependent systemic microvascular reactivity improved after recovery from COVID-19 in patients with cardiovascular diseases, in parallel with a reduction in the levels of several serum cytokines and chemokines involved in the regulation of vascular function and inflammation.

Abstract 14718: Using Renal-Specific Cyclo-Oxygenase-2-Deficient Mice to Understand the Pro-Thrombotic Effects of Non-Steroidal Anti-Inflammatory Drugs

Introduction: Non-steroidal anti-inflammatory drugs (NSAIDs) work by inhibiting the enzyme cyclooxygenase (COX)2 but their use increases thrombotic risk. We have shown that COX2 inhibition increases plasma methylarginines ADMA and LNMMA in mice and man. Methylarginines are controlled in the kidney but circulate causing inhibition of anti-thrombotic vascular NO by competing with L-arginine for the active site of eNOS. However, the causative links between renal COX2 (which is expressed predominately in fibroblasts), methylarginines and thrombosis remain unproven. Hypothesis: Here we hypothesised that deletion of COX2 from fibroblasts would result in a renal-specific COX2-deficiency and be sufficient to increase methylarginine levels and drive vascular NO dysfunction and a pro-thrombotic phenotype. Methods: Fibroblast COX2-deficient mice were generated from Fsp1-Cre and Ptgs2 flox strains. COX2 levels were measured by RT-qPCR, methylarginines by LC/MS/MS, vascular NO function as acetylcholine-induced dilation by myography and thrombosis in vivo after FeCl 3 -carotid injury. Results: Fibroblast COX2-deficient mice showed reduced COX2 expression in the renal medulla (Fig A) but not renal cortex, aorta, lung, colon, thymus or brain. This was associated with increased plasma ADMA and LNMMA levels (Fig B) and reduced NO-dependent dilatation of carotid arteries (Fig C). Fibroblast COX2-deficiency accelerated thrombosis after carotid artery injury which could be reversed by pre-treating animals with L-arginine (50mg/kg; 5 days) which displaces methylarginines from eNOS (Fig D). Conclusions: These data provide the first direct demonstration that renal COX2 regulates methylarginine levels to control systemic endothelial and thrombotic function. As such, they indicate that inhibition of renal COX2 contributes to the thrombotic risk seen in patients taking NSAIDs and suggest L-arginine supplementation as a potential rescue therapy to mitigate this.

Systemic Endothelial Function, Plasma Xanthine Oxidoreductase Activity, and Blood Pressure Variability in Patients with Stable Coronary Artery Disease.

Background and Objectives: Although previous studies showed that an activity of xanthine oxidoreductase (XOR), a rate-limiting enzyme in purine metabolism, beyond the serum uric acid level, was associated with the development of coronary artery disease (CAD), the underlying mechanisms are unclear. Because endothelial dysfunction and a greater blood pressure (BP) variability may play a role, we investigated the relations among the endothelial function, XOR, and BP variability. Materials and Methods: This was a post-hoc study using pooled data of patients with a stable CAD from two prospective investigations, in which the systemic endothelial function was assessed with the reactive hyperemia index (RHI) and the XOR activity was measured. The BP variability was evaluated using BP measurements during the three- and four-day hospitalization. Results: A total of 106 patients with a stable CAD undergoing a percutaneous coronary intervention were included. Of the 106 patients, 46 (43.4%) had a systemic endothelial dysfunction (RHI < 1.67). The multivariable analysis identified a higher body mass index (BMI), female gender, and diabetes as factors associated with an endothelial dysfunction. A higher BMI was also related to an elevated XOR activity, in addition to current smoking. No significant correlation was observed between the RHI and XOR activity. Similarly, the in-hospital BP variability was associated with neither the endothelial function nor XOR. Conclusions: Among patients with a stable CAD, several factors were identified as being associated with a systemic endothelial dysfunction or an elevated XOR activity. However, no direct relations between the endothelial function, XOR, and BP variability were found.

Correlation between endothelial dysfunction and occurrence of no-reflow in patients undergoing post-thrombolysis early invasive percutaneous intervention for ST-elevation myocardial infarction

BackgroundEndothelial dysfunction and no-reflow share microcirculatory obstruction as a common pathophysiological mechanism. This study evaluated the relationship between systemic peripheral endothelial dysfunction assessed by flow-mediated dilatation (FMD) of the brachial artery and no-reflow in patients with ST-segment elevation myocardial infarction (STEMI) who received successful fibrinolysis.ResultsThis study included 150 patients managed by the percutaneous coronary intervention (PCI) after successful fibrinolysis. Patients were divided according to coronary angiographic success into normal flow versus no-reflow groups. According to FMD measured through brachial artery ultrasound, patients were divided based on their endothelial function into endothelial dysfunction versus normal endothelial function. No-reflow occurred in 44 patients (29.3%). No-reflow patients had longer pain to door time (6.52 ± 1.82 vs 5.19 ± 1.85 h), more Killip class II (36.4% vs 16%, p = 0.006), and lower FMD (7.26 ± 1.92 vs 8.23 ± 2.76%, p = 0.036). Also, they showed more endothelial dysfunction; however, this difference was statistically nonsignificant (97.7% vs 87.7%, p = 0.055). One hundred and thirty-six patients (90.7%) had endothelial dysfunction. They were older (57.51 ± 5.92 vs 50.86 ± 4.55 years, p value ≤ 0.001), more smokers (41.2% vs 14.3%, p = 0.04). Patients with normal endothelial function had a more myocardial blush grade (MBG) 3 (78.6% vs 26.5%, p value = 0.001) in comparison with more MBG 2 in those with endothelial dysfunction (41.9% vs 14.3%, p value = 0.001). Endothelial dysfunction patients had nonsignificant more no-reflow (31.6% vs 7.1%, p-value: 0.06). There was a significant weak positive correlation between thrombolysis in myocardial infarction (TIMI) flow and FMD (r = 0.174, p = 0.033) and a significant moderate positive correlation between MBG and FMD (r = 0.366, p < 0.001). Patients with TIMI I flow had significantly lower FMD compared with patients with TIMI II and TIMI III flow post-PCI. FMD ≤ 6% could predict post-procedural TIMI I flow.ConclusionsIn STEMI patients who underwent PCI within 24 h after successful fibrinolysis, those who had no-reflow showed worse peripheral systemic endothelial function as they had lower brachial artery FMD. Also, FMD showed a significant positive correlation with the post-procedural angiographic flow (TIMI flow and MBG). FMD ≤ 6% could predict TIMI I flow.

Determination of Lipoxygenase, CYP450, and Non-Enzymatic Metabolites of Arachidonic Acid in Essential Hypertension and Type 2 Diabetes.

Type 2 diabetes (T2D) and hypertension (HTN) are common risk factors of cardiovascular diseases (CVD) characterized by chronic low-grade systemic inflammation and impaired endothelial function. This study aimed to assess whether levels of non-enzymatic, lipoxygenase (LOX)- and cytochrome P450 (CYP)-derived arachidonic acid (ARA) metabolites, which are known regulators of vascular homeostasis, are affected by HTN and T2D. For this objective, 17 plasma level derivatives of ARA were quantitated by chromatography coupled with mass spectrometry in 44 patients (12 healthy, 8 HTN, 7 T2D, and 17 HTN + T2D). Effects of hyperglycemic and hyperinsulinemic clamps on ARA metabolite levels were assessed in seven healthy subjects. No significant differences in the plasma levels of ARA metabolites were observed for T2D patients compared with healthy volunteers. HTN was associated with an alteration of ARA metabolite correlation patterns with increased 20-, 19-, 15-, and 8-hydroxyeicosatrienoic acid (HETE). A decrease of 20-HETE was also observed during both hyperglycemic and hyperinsulinemic clamps. Additional experiments are needed to assess whether the modulation of HETE metabolites in HTN may be of interest. Furthermore, although not affected by T2D, it remains to investigate whether the decrease of 20-HETE observed during clamps may be related to the regulation of glucose tolerance and insulin signaling.

Endothelial NO synthase 786T/T polymorphism increases hemorrhagic transformation after endovascular thrombectomy

Background and purposeThis study examined whether the 786 NOS3 polymorphism is associated with the risk of hemorrhagic transformation (HT) in stroke patients with anterior large vessel occlusion (ALVO) treated using endovascular thrombectomy (EVT). MethodsWe performed an observational cohort study that included 118 patients with ALVO who underwent EVT. HT was assessed in follow-up CT and MRI. HT and non-HT patients were compared in terms of the 786 NOS3 polymorphism, flow mediated dilation (FMD) values within 3 days after the stroke, and collateral status based on three grading scales. Demographics, vascular risk factors, additional radiological data including ASPECT score, thrombus length and infarct size, and EVT procedure and outcome variables were also included. ResultsRadiological HT occurred in 55 (46.6%) patients and the 786T/T NOS3 polymorphism was associated with HT (unadjusted OR of 2.33, 95%CI: 1.05–5.20, adjusted OR of 3.14, 95%CI: 1.16–8.54). Collateral status and systemic endothelial function assessed by FMD were not mediators of this relationship as no differences were seen in the median FMD percentage values or collateral status between NOS3 genotypes. ConclusionsOur results suggest that genetic variations affecting the NO pathway, such as the 786 NOS3 polymorphism, may contribute to individual variability in the occurrence of HT and these results support involvement of this pathway in the pathogenesis of ischemia-reperfusion injury after EVT.

ENDOTHELIAL COMPLICATIONS IN HYPERTENSIVE PATIENTS WITH OBESITY OR NORMAL BODY WEIGHT AFTER COVID-19

Objective: To study the contribution of a COVID-19 to endothelial dysfunction in hypertensive patients with obesity or normal body weight. Design and method: 59 hypertensive patients, male and female, aged 20–50 years (40.2 ± 6.7 years), with blood pressure (BP) under control, without diabetes, non-smokers were included in the study. All of them were divided into three groups: I (n = 13) - patients with obesity (body mass index (BMI) &gt; 30 kg/m2) and 1 month after COVID-19; II (n = 11) - patients with normal body weight (BMI &lt; 25 kg/m2) and 1 month after COVID-19; III (n = 25) - patients with obesity (BMI &gt; 30 kg/m2) without COVID-19. Patients of Ith and IIIth groups were comparable in BMI and BP levels. LDL-cholesterol and triglycerides levels, office systolic BP and diastolic BP, flow-mediated dilation (FMD) study to assessed endothelial function, were performed in all groups. Calculation was done with software STATISTICA 6.0. Results: Post-COVID-19 patients with obesity had significantly higher levels LDL-cholesterol and triglycerides, systolic BP and diastolic BP then in post-COVID-19 patients with normal body weight: 3.5 ± 0.7 mmol/l vs 3.02 ± 0.62 mmol/l (p &lt; 0.05), 3.5 ± 2.9 mmol/l vs 1.10 ± 0.3 mmol/l (p &lt; 0.05), 141 ± 9.6 mmHg vs 123 ± 10.3 mmHg (p &lt; 0.05), 89.5 ± 10.01 mmHg vs 76 ± 8.8 mmHg (p &lt; 0.05) respectively. FMD were significantly lower in patients with obesity and COVID-19 (3.6 ± 2.9%, p &lt; 0.05) then in patients with normal body weight and COVID-19 (8.7 ± 3.4%, p &lt; 0,05) and in patients with obesity without COVID-19 (4.2 ± 3.6%, p &lt; 0.05). Conclusions: Our study highlights that chronic impairment of systemic vascular endothelial function in patients with obesity, when intensified by the detrimental effects of SARS-CoV-2 over the endothelium, may explain their worse outcomes in COVID-19. However, obesity itself is one of important factors contributing to deterioration of endothelial function.

Cerebrovascular function and its association with systemic artery function and stiffness in older adults with and without mild cognitive impairment

PurposeOur aim was to compare cerebrovascular and systemic vascular function between older adults with and without mild cognitive impairment (MCI), and to determine which measures of vascular function best predict the presence of MCI.MethodsIn 41 adults with MCI and 33 adults without MCI (control) we compared middle cerebral artery velocity (MCAv) and cerebrovascular pulsatility index (PI) at rest, cerebrovascular reactivity to CO2, and responsiveness to changes in blood pressure (%∆MCAv/%∆MAP). Systemic vascular function was assessed by flow-mediated dilation (FMD) and stiffness by pulse wave velocity (PWV).ResultsCerebrovascular PI was higher in MCI compared with control (mean ± SD: 1.17 ± 0.27 vs. 1.04 ± 0.21), and MCI exhibited a lower %∆MCAv/%∆MAP (1.26 ± 0.44 vs. 1.50 ± 0.55%). Absolute (p = 0.76) and relative cerebrovascular reactivity to CO2 (p = 0.34) was similar between MCI and control. When age was included as a covariate the significant difference in cerebral PI between groups was lost. PWV was higher (13.2 ± 2.2 vs. 11.3 ± 2.5 m s−1) and FMD% (4.41 ± 1.70 vs. 5.43 ± 2.15%) was lower in MCI compared with control. FMD% was positively associated with PI across the cohort. Logistic regression analysis indicated that FMD and PWV significantly discriminated between MCI and controls, independent of age, whereas the inclusion of cerebrovascular measures did not improve the predictive accuracy of the model.ConclusionThese findings raise the possibility that early changes in systemic vascular stiffness and endothelial function may contribute to altered cerebrovascular haemodynamics and impaired cognitive function, and present potential targets for prevention and treatment strategies in people with MCI.

Curcumin Enhances Fed-State Muscle Microvascular Perfusion but Not Leg Glucose Uptake in Older Adults.

Therapeutic interventions aimed at enhancing blood flow may combat the postprandial vascular and metabolic dysfunction that manifests with chronological ageing. We compared the effects of acute curcumin (1000 mg) coupled with an oral nutritional supplement (ONS, 7.5 g protein, 24 g carbohydrate and 6 g fat) versus a placebo and ONS (control) on cerebral and leg macrovascular blood flow, leg muscle microvascular blood flow, brachial artery endothelial function, and leg insulin and glucose responses in healthy older adults (n = 12, 50% male, 73 ± 1 year). Curcumin enhanced m. tibialis anterior microvascular blood volume (MBV) at 180 and 240 min following the ONS (baseline: 1.0 vs. 180 min: 1.08 ± 0.02, p = 0.01 vs. 240 min: 1.08 ± 0.03, p = 0.01), and MBV was significantly higher compared with the control at both time points (p < 0.05). MBV increased from baseline in the m. vastus lateralis at 240 min after the ONS in both groups (p < 0.05), and there were no significant differences between groups. Following the ONS, leg blood flow and leg vascular conductance increased, and leg vascular resistance decreased similarly in both conditions (p < 0.05). Brachial artery flow-mediated dilation and middle cerebral artery blood flow were unchanged in both conditions (p > 0.05). Similarly, the curcumin and control groups demonstrated comparable increases in glucose uptake and insulin in response to the ONS. Thus, acute curcumin supplementation enhanced ONS-induced increases in m. tibialis anterior MBV without potentiating m. vastus lateralis MBV, muscle glucose uptake, or systemic endothelial or macrovascular function in healthy older adults.