Current topic of vascular function in hypertension.

Vascular function assessment is useful for the evaluation of atherosclerosis severity, which may provide additional information for cardiovascular risk stratification. In addition, vascular function assessment is helpful for a better understanding of pathophysiological associations between vascular dysfunction and cardiometabolic disorders. In 2020 and 2021, although coronavirus disease 2019 (COVID-19) was still a worldwide challenge for health care systems, many excellent articles regarding vascular function were published in Hypertension Research and other major cardiovascular and hypertension journals. In this review, we summarize new findings on vascular function and discuss the association between vascular function and COVID-19, the importance of lifestyle modifications for the maintenance of vascular function, and the usefulness of vascular function tests for cardiovascular risk assessment. We hope this review will be helpful for the management of cardiovascular risk factors, including hypertension and cardiovascular diseases, in clinical practice.

Study protocol of a randomized controlled clinical trial investigating the effects of omega-3 supplementation on endothelial function, vascular structure, and metabolic parameters in adolescents with type 1 diabetes.

BACKGROUND: Type 1 diabetes is a main health burden with several related comorbidities. It has been shown that endothelial function, vascular structure, and metabolic parameters are considerably disrupted in patients with type 1 diabetes. Omega-3 as an adjuvant therapy may exert profitable effects on type 1 diabetes and its complications by improving inflammation, oxidative stress, immune responses, and metabolic status. Because no randomized clinical trial has examined the effects of omega-3 consumption in children and adolescents with type 1 diabetes; the present study aims to close this gap. METHODS: This investigation is a randomized clinical trial, in which sixty adolescents with type 1 diabetes will be randomly assigned to receive either omega-3 (600 mg/day) or placebo capsules for 12 weeks. Evaluation of anthropometric parameters, flow-mediated dilation (FMD) as an endothelial function marker, carotid intima-media thickness (CIMT) as a vascular structure marker, proteinuria, biochemical factors including glycemic and lipid profile, blood urea nitrogen (BUN), creatinine, high-sensitivity C-reactive protein (hs-CRP), and erythrocyte sedimentation rate (ESR), as well as blood pressure will be done at the baseline and end of the trial. Also, dietary intake and physical activity will be assessed throughout the study. Statistical analysis will be performed using the SPSS software (Version 24), and P < 0.05 will be considered statistically meaningful. DISCUSSION: It is hypothesized that omega-3 supplementation may be beneficial for the management of type 1 diabetes and its complications by reducing inflammation and oxidative stress and also modulating immune responses and glucose and lipid metabolism through various mechanisms. The present study aims to investigate any effect of omega-3 on patients with type 1 diabetes. ETHICAL ASPECTS: This trial received approval from Medical Ethics Committee of Iran University of Medical Sciences, Tehran, Iran (IR.IUMS.REC.1400.070). TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20210419051010N1 . Registered on 29 April 2021.

The effect of ozone short-term exposure on flow-mediated dilation: Using data before and after COVID-19 lockdown in Shanghai.

BACKGROUND: Short-term ambient ozone exposure has been shown to have an adverse impact on endothelial function, contributing to major cardiovascular diseases and premature death. However, only limited studies have focused on the impact of short-term ozone exposure on Flow-mediated Dilation (FMD), and their results have been inconsistent. The current study aims to explore the relationship between short-term ambient ozone exposure and FMD. In addition, the study aims to investigate how lockdown measures for COVID-19 may influence ozone concentration in the atmosphere. METHODS: Participants were recruited from a hospital in Shanghai from December 2020 to August 2022. Individuals' ozone exposure was determined using residential addresses. A distributed lag nonlinear model was adopted to assess the exposure-response relationship between short-term ozone exposure and FMD. A comparison was made between ambient ozone concentration and FMD data collected before and after Shanghai's lockdown in 2022. RESULTS: When ozone concentration was between 150 and 200 µg/m3, there was a significant reduction in FMD with a 2-day lag. Elderly individuals (age ≥ 65), females, non-drinkers, and non-smokers were found to be more susceptible to high concentrations of ozone exposure. The lockdown did elevate ambient ozone concentration compared to the same period previously. INTERPRETATION: This study proposes that an ambient ozone concentration of 150-200 µg/m3 is harmful to endothelial function, and that a reduction in human activity during lockdown increased the concentration, which in turn reduced FMD. However, the underlying mechanism requires further research.

Uphill versus downhill high-intensity training effectiveness in preserving vascular function and exercise performance in runners who reduce their regular endurance training.

Purpose: The COVID-19 restrictions have limited outdoor physical activities. High-intensity training (HIT) may be a valid indoor alternative. We tested whether an indoor HIT is effective in maintaining vascular function and exercise performance in runners who reduce their usual endurance training, and whether a downhill HIT is as effective as an uphill one for such purposes. Methods: Sixteen runners performed the same 6-week HIT either uphill (UP, eight runners) or downhill (DOWN, eight runners). Eight runners continuing their usual endurance training acted as a control group (CON). The following data were collected before vs after our HIT: vascular conductance during rapid leg vasodilation to assess vasodilation capacity; V̇O2max through running incremental test to exhaustion; 2000 m running time; neuromuscular indexes related to lower-limb muscle strength. Results: Both uphill and downhill HIT failed in maintaining the pre-HIT leg vasodilation capacity compared to CON, which was, however, blunted more after uphill than downhill HIT. V̇O2max and 2000 m time were similar after downhill HIT compared to CON, and augmented after uphill HIT compared to CON and DOWN. Indexes of lower-limb muscle strength were similar before vs after HIT and among groups. Conclusion: Our HIT was ineffective in maintaining the pre-HIT leg vasodilation capacity compared to runners continuing their usual low-intensity endurance training, but did not lead to reductions in V̇O2max, 2000 m time performance, and indexes related to lower-limb muscle strength. Our data show an appealing potential for preserving exercise performance with low cardiorespiratory effort via downhill running.

Plasma bioactive adrenomedullin on intensive care unit admission is associated with acute respiratory distress syndrome: an observational study.

BACKGROUND: Bioactive adrenomedullin (bio-ADM) is a vasoactive peptide with a key role in reducing vascular hyperpermeability and improving endothelial stability during infection, but it also has vasodilatory properties. Bioactive ADM has not been studied in conjunction with acute respiratory distress syndrome (ARDS), but it has recently been shown to correlate with outcomes after severe COVID-19. Therefore, this study investigated the association between circulating bio-ADM on intensive care unit (ICU) admission and ARDS. The secondary aim was the association between bio-ADM and ARDS mortality. METHODS: We analysed bio-ADM levels and assessed the presence of ARDS in adult patients admitted to two general intensive care units in southern Sweden. Medical records were manually screened for the ARDS Berlin criteria. The association between bio-ADM levels and ARDS and mortality in ARDS patients was analysed using logistic regression and receiver-operating characteristics analysis. The primary outcome was an ARDS diagnosis within 72 h of ICU admission, and the secondary outcome was 30-day mortality. RESULTS: Out of 1224 admissions, 11% (n = 132) developed ARDS within 72 h. We found that elevated admission bio-ADM level was associated with ARDS independently of sepsis status and of organ dysfunction as measured by the Sequential organ failure assessment (SOFA) score. Both lower levels (< 38 pg/L) and high (> 90 pg/L) levels of bio-ADM were independently (of the Simplified acute physiology score, SAPS-3) predictive of mortality. Patients with indirect mechanisms of lung injury had higher bio-ADM levels than those with a direct mechanism of injury, and bio-ADM increased with increasing ARDS severity. CONCLUSIONS: High levels of bio-ADM on admission are associated with ARDS, and bio-ADM levels significantly differ depending on the injury mechanism. In contrast, both high and low levels of bio-ADM are associated with mortality, possibly due to the dual action of bio-ADM in stabilising the endothelial barrier and causing vasodilation. These findings could lead to improved diagnostic accuracy of ARDS and potentially lead to new therapeutic strategies.

Endothelial dysfunction in acute and long standing COVID-19: A prospective cohort study.

BACKGROUND: Coronavirus disease-19 (COVID-19) is implicated by active endotheliitis, and cardiovascular morbidity. The long-COVID-19 syndrome implications in atherosclerosis have not been elucidated yet. We assessed the immediate, intermediate, and long-term effects of COVID-19 on endothelial function. METHODS: In this prospective cohort study, patients hospitalized for COVID-19 at the medical ward or Intensive Care Unit (ICU) were enrolled and followed up to 6 months post-hospital discharge. Medical history and laboratory examinations were performed while the endothelial function was assessed by brachial artery flow-mediated dilation (FMD). Comparison with propensity score-matched cohort (control group) was performed at the acute (upon hospital admission) and follow-up (1 and 6 months) stages. RESULTS: Seventy-three patients diagnosed with COVID-19 (37% admitted in ICU) were recruited. FMD was significantly (p < 0.001) impaired in the COVID-19 group (1.65 ± 2.31%) compared to the control (6.51 ± 2.91%). ICU-treated subjects presented significantly impaired (p = 0.001) FMD (0.48 ± 1.01%) compared to those treated in the medical ward (2.33 ± 2.57%). During hospitalization, FMD was inversely associated with Interleukin-6 and Troponin I (p < 0.05 for all). Although, a significant improvement in FMD was noted during the follow-up (acute: 1.75 ± 2.19% vs. 1 month: 4.23 ± 2.02%, vs. 6 months: 5.24 ± 1.62%; p = 0.001), FMD remained impaired compared to control (6.48 ± 3.08%) at 1 month (p < 0.001) and 6 months (p = 0.01) post-hospital discharge. CONCLUSION: COVID-19 patients develop a notable endothelial dysfunction, which is progressively improved over a 6-month follow-up but remains impaired compared to healthy controls subjects. Whether chronic dysregulation of endothelial function following COVID-19 could be accompanied by a residual risk for cardiovascular and thrombotic events merits further research.

Analytical performance evaluation of bioactive adrenomedullin on point-of-care platform

For matrix comparison, EDTA whole blood samples (freshly collected and stored at 2-8 °C until the testing) from ten healthy donors were spiked with synthetic bio-ADM to achieve two bio-ADM levels per donor spanning the measuring range. The analytical performance evaluation was mainly conducted using frozen and contrived plasma samples and to validate bio-ADM measurements with IB10 sphingotest SP ® sp bio-ADM SP ® sp . Keywords: acute care;bioactive adrenomedullin;critical care biomarker;endothelial function;Nexus IB10;point-of-care platform EN acute care bioactive adrenomedullin critical care biomarker endothelial function Nexus IB10 point-of-care platform e13 e16 4 11/28/22 20230101 NES 230101 To the Editor, Biologically active adrenomedullin (bio-ADM) is a peptide hormone that regulates the endothelial barrier function [[1]], [[2]], [[3]]. [Extracted from the article]

Biological Assessment of the NO-Dependent Endothelial Function.

Nitric oxide (NO) is implicated in numerous physiological processes, including vascular homeostasis. Reduced NO bioavailability is a hallmark of endothelial dysfunction, a prequel to many cardiovascular diseases. Biomarkers of an early NO-dependent endothelial dysfunction obtained from routine venous blood sampling would be of great interest but are currently lacking. The direct measurement of circulating NO remains a challenge due by its high reactivity and short half-life. The current techniques measure stable products from the NO signaling pathway or metabolic end products of NO that do not accurately represent its bioavailability and, therefore, endothelial function per se. In this review, we will concentrate on an original technique of low temperature electron paramagnetic resonance spectroscopy capable to directly measure the 5-α-coordinated heme nitrosyl-hemoglobin in the T (tense) state (5-α-nitrosyl-hemoglobin or HbNO) obtained from fresh venous human erythrocytes. In humans, HbNO reflects the bioavailability of NO formed in the vasculature from vascular endothelial NOS or exogenous NO donors with minor contribution from erythrocyte NOS. The HbNO signal is directly correlated with the vascular endothelial function and inversely correlated with vascular oxidative stress. Pilot studies support the validity of HbNO measurements both for the detection of endothelial dysfunction in asymptomatic subjects and for the monitoring of such dysfunction in patients with known cardiovascular disease. The impact of therapies or the severity of diseases such as COVID-19 infection involving the endothelium could also be monitored and their incumbent risk of complications better predicted through serial measurements of HbNO.

Hypoxic pulmonary vascular response can screen subclinical lifestyle disease in healthy population.

OBJECTIVE: Subclinical life style disease can cause endothelial dysfunction associated with perfusion abnormalities and reduced vascular compliance. Subclinical elevated beta type natriuretic peptide (BNP) has been associated with altered fluid shift from extra to intracellular space during acute hypoxia. Therefore we measured vascular response and BNP levels during acute hypoxia to study endothelial functions among healthy individuals. METHODS: Individuals were exposed to acute normobaric hypoxia of FiO2 = 0.15 for one hour in supine position and their pulmonary and systemic vascular response to hypoxia was compared. Individuals were divided into two groups based on either no response (Group 1) or rise in systolic pulmonary artery pressure to hypoxia (Group 2) and their BNP levels were compared. RESULTS: BNP was raised after hypoxia exposure in group 2 only from 18.52 ± 7 to 21.56 ± 10.82 picogram/ml, p < 0.05. Group 2 also showed an increase in mean arterial pressure and no fall in total body water in response to acute hypoxia indicating decreased endothelial function compared to Group 1. CONCLUSION: Rise in pulmonary artery pressure and BNP level in response to acute normobaric hypoxia indicates reduced endothelial function and can be used to screen subclinical lifestyle disease among healthy population.

Vaccination Against SARS-CoV-2 Protects from COVID-19-induced Endothelial Dysfunction.

BACKGROUND: Coronavirus Disease-19 (COVID-19) is implicated in endotheliitis, which adversely affects cardiovascular events. The impact of vaccination with COVID-19 on the clinical outcome of patients is documented. OBJECTIVE: To evaluate the impact of vaccination with COVID-19 on the severe acute respiratory syndrome, coronavirus-2 (SARS-CoV-2) infection-related endothelial impairment. METHODS: We enrolled 45 patients hospitalized for COVID-19 (either vaccinated or not against SARS-CoV-2). Clinical and laboratory data were collected, and brachial artery flow-mediated dilation (FMD) was evaluated. Subjects without COVID-19 were used as the control group. RESULTS: There was no difference in age (64.7 ± 7.5 years vs. 61.2 ± 11.1 years vs. 62.4 ± 9.5, p = 0.28), male sex (49% vs. 60% vs. 52%, p = 0.71), control subjects, vaccinated, and unvaccinated subjects with COVID-19, respectively. Of the patients with COVID-19, 44% were vaccinated against SARS-CoV-2. Unvaccinated COVID-19 patients had significantly impaired FMD compared to vaccinated COVID-19 patients and Control subjects (2.05 ± 2.41 % vs. 7.24 ± 2.52% vs. 7.36 ± 2.94 %, p <0.001). Importantly, post hoc tests revealed that unvaccinated COVID-19 patients had significantly impaired FMD from both Vaccinated COVID-19 subjects (p <0.001) and from Control subjects (p <0.001). There was no difference in FMD between the control group and the vaccinated COVID-19 group (p = 0.99). CONCLUSION: Hospitalized patients with COVID-19 present endothelial dysfunction in the acute phase of the disease. Endothelial function in unvaccinated patients with COVID-19 is impaired compared to control subjects as well compared to vaccinated patients with COVID-19. Vaccinated hospitalized subjects with COVID-19 do not show endothelial dysfunction, strengthening the protective role of vaccination against SARS-CoV-2.

Post COVID-19 syndrome with impairment of flow-mediated epicardial vasodilation and flow reserve.

AIMS: The aim of this study is to evaluate whether post-acute sequelae of COVID-19 cardiovascular syndrome (PASC-CVS) is associated with alterations in coronary circulatory function. MATERIALS AND METHODS: In individuals with PASC-CVS but without known cardiovascular risk factors (n = 23) and in healthy controls (CON, n = 23), myocardial blood flow (MBF) was assessed with 13 N-ammonia and PET/CT in mL/g/min during regadenoson-stimulated hyperemia, at rest, and the global myocardial flow reserve (MFR) was calculated. MBF was also measured in the mid and mid-distal myocardium of the left ventricle (LV). The Δ longitudinal MBF gradient (hyperemia minus rest) as a reflection of an impairment of flow-mediated epicardial vasodilation, was calculated. RESULTS: Resting MBF was significantly higher in PASC-CVS than in CON (1.29 ± 0.27 vs. 1.08 ± 0.20 ml/g/min, p ≤ .024), while hyperemic MBFs did not differ significantly among groups (2.46 ± 0.53 and 2.40 ± 0.34 ml/g/min, p = .621). The MFR was significantly less in PASC-CVS than in CON (1.97 ± 0.54 vs. 2.27 ± 0.43, p ≤ .031). In addition, there was a Δ longitudinal MBF gradient in PASC-CVS, not observed in CON (-0.17 ± 0.18 vs. 0.04 ± 0.11 ml/g/min, p < .0001). CONCLUSIONS: Post-acute sequelae of COVID-19 cardiovascular syndrome may be associated with an impairment of flow-mediated epicardial vasodilation, while reductions in coronary vasodilator capacity appear predominantly related to increases in resting flow in women deserving further investigations.

VASCOVID: Hybrid diffuse optical platform combined with a pulse-oximeter and an automatized inflatable tourniquet for the assessment of metabolism and endothelial health in the intensive care

VASCOVID project is developing and testing a hybrid diffuse optical monitor for evaluating endothelial function and metabolism in intensive care including COVID-19. © 2022 The Authors.

The Role of Microparticles in Polycystic Ovarian Syndrome. An Updated Review

Microparticles (MPs) are vesicles of less than 1 mu m in diameter (submicron vesicles) shed from plasma membranes to cell activation, injury, and apoptosis response. They consisted of membrane proteins and cytosolic material from the cell they originated. These vesicles are vital mediators of pathological and physiological cellular processes. Polycystic ovary syndrome (PCOS) is a regular endocrine, menstrual and metabolic condition that affects 10-15% of females in their reproductive period. Numerous researches have described the association between low-grade chronic inflammation and PCOS;however, the relation is not well understood. Chronic lowgrade inflammation is reflected as a risk factor for cardiovascular disease, atherosclerosis, and endothelial dysfunction, and it is linked to abdominal obesity and insulin resistance (IR). MPs may be useful biomarkers for the early detection of cardiovascular disease and thrombosis in PCOS patients. In March 2020, the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) became pandemic, wreaking havoc on healthcare systems worldwide and the global economy. Obesity, diabetes, and cardiovascular disease have all been linked to COVID-19 increased risk of infection. PCOS patients have recently been identified as an underserved and potentially high-risk demographic for COVID-19 problems. This article tried to review and present recent studies that explored the role of microparticles in polycystic ovarian syndrome.

Impact of breakthrough COVID-19 cases during the omicron wave on vascular health and cardiac autonomic function in young adults.

We and others have previously shown that COVID-19 results in vascular and autonomic impairments in young adults. However, the newest variant of COVID-19 (Omicron) appears to have less severe complications. Therefore, we investigated whether recent breakthrough infection with COVID-19 during the Omicron wave impacts cardiovascular health in young adults. We hypothesized that measures of vascular health and indices of cardiac autonomic function would be impaired in those who had the Omicron variant of COVID-19 when compared with controls who never had COVID-19. We studied 23 vaccinated adults who had COVID-19 after December 25, 2021 (Omicron; age, 23 ± 3 yr; 14 females) within 6 wk of diagnosis compared with 13 vaccinated adults who never had COVID-19 (age, 26 ± 4 yr; 7 females). Macro- and microvascular function were assessed using flow-mediated dilation (FMD) and reactive hyperemia, respectively. Arterial stiffness was determined as carotid-femoral pulse wave velocity (cfPWV) and augmentation index (AIx). Heart rate (HR) variability and cardiac baroreflex sensitivity (BRS) were assessed as indices of cardiac autonomic function. FMD was not different between control (5.9 ± 2.8%) and Omicron (6.1 ± 2.3%; P = 0.544). Similarly, reactive hyperemia (P = 0.884) and arterial stiffness were not different between groups (e.g., cfPWV; control, 5.9 ± 0.6 m/s and Omicron, 5.7 ± 0.8 m/s; P = 0.367). Finally, measures of HR variability and cardiac BRS were not different between groups (all, P > 0.05). Collectively, these data suggest preserved vascular health and cardiac autonomic function in young, otherwise healthy adults who had breakthrough cases of COVID-19 during the Omicron wave.NEW & NOTEWORTHY We show for the first time that breakthrough cases of COVID-19 during the Omicron wave does not impact vascular health and cardiac autonomic function in young adults. These are promising results considering earlier research showing impaired vascular and autonomic function following previous variants of COVID-19. Collectively, these data demonstrate that the recent Omicron variant is not detrimental to cardiovascular health in young, otherwise healthy, vaccinated adults.

A biological rationale for the disparate effects of omega-3 fatty acids on cardiovascular disease outcomes.

The omega-3 fatty acids (n3-FAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) rapidly incorporate into cell membranes where they modulate signal transduction pathways, lipid raft formation, and cholesterol distribution. Membrane n3-FAs also form specialized pro-resolving mediators and other intracellular oxylipins that modulate inflammatory pathways, including T-cell differentiation and gene expression. Cardiovascular (CV) trials have shown that EPA, administered as icosapent ethyl (IPE), reduces composite CV events, along with plaque volume, in statin-treated, high-risk patients. Mixed EPA/DHA regimens have not shown these benefits, perhaps as the result of differences in formulation, dosage, or potential counter-regulatory actions of DHA. Indeed, EPA and DHA have distinct, tissue-specific effects on membrane structural organization and cell function. This review summarizes: (1) results of clinical outcome and imaging trials using n3-FA formulations; (2) membrane interactions of n3-FAs; (3) effects of n3-FAs on membrane oxidative stress and cholesterol crystalline domain formation during hyperglycemia; (4) n3-FA effects on endothelial function; (5) role of n3-FA-generated metabolites in inflammation; and (6) ongoing and future clinical investigations exploring treatment targets for n3-FAs, including COVID-19.

Persistent Endothelial Dysfunction in Coronavirus Disease-2019 Survivors Late After Recovery.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can result in an endothelial dysfunction in acute phase. However, information on the late vascular consequences of COVID-19 is limited. METHODS: Brachial artery flow-mediated dilation (FMD) examination were performed, and inflammatory biomarkers were assessed in 86 survivors of COVID-19 for 327 days (IQR 318-337 days) after recovery. Comparisons were made with 28 age-matched and sex-matched healthy controls and 30 risk factor-matched patients. RESULTS: Brachial artery FMD was significantly lower in the survivors of COVID-19 than in the healthy controls and risk factor-matched controls [median (IQR) 7.7 (5.1-10.7)% for healthy controls, 6.9 (5.5-9.4)% for risk factor-matched controls, and 3.5(2.2-4.6)% for COVID-19, respectively, p < 0.001]. The FMD was lower in 25 patients with elevated tumor necrosis factor (TNF)-α [2.7(1.2-3.9)] than in 61 patients without elevated TNF-α [3.8(2.6-5.3), p = 0.012]. Furthermore, FMD was inversely correlated with serum concentration of TNF-α (r = -0.237, p = 0.007). CONCLUSION: Survivors of COVID-19 have a reduced brachial artery FMD, which is inversely correlated with increased serum concentration of TNF-α. Prospective studies on the association of endothelial dysfunction with long-term cardiovascular outcomes, especially the early onset of atherosclerosis, are warranted in survivors of COVID-19.

Endothelial Dysfunction in COVID-19: A Unifying Mechanism and a Potential Therapeutic Target.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) generated a worldwide emergency, until the declaration of the pandemic in March 2020. SARS-CoV-2 could be responsible for coronavirus disease 2019 (COVID-19), which goes from a flu-like illness to a potentially fatal condition that needs intensive care. Furthermore, the persistence of functional disability and long-term cardiovascular sequelae in COVID-19 survivors suggests that convalescent patients may suffer from post-acute COVID-19 syndrome, requiring long-term care and personalized rehabilitation. However, the pathophysiology of acute and post-acute manifestations of COVID-19 is still under study, as a better comprehension of these mechanisms would ensure more effective personalized therapies. To date, mounting evidence suggests a crucial endothelial contribution to the clinical manifestations of COVID-19, as endothelial cells appear to be a direct or indirect preferential target of the virus. Thus, the dysregulation of many of the homeostatic pathways of the endothelium has emerged as a hallmark of severity in COVID-19. The aim of this review is to summarize the pathophysiology of endothelial dysfunction in COVID-19, with a focus on personalized pharmacological and rehabilitation strategies targeting endothelial dysfunction as an attractive therapeutic option in this clinical setting.

Cardiopulmonary Exercise Performance and Endothelial Function in Convalescent COVID-19 Patients.

BACKGROUND: Endothelial dysfunction has been proposed as the common pathogenic background of most manifestations of coronavirus disease 2019 (COVID-19). Among these, some authors also reported an impaired exercise response during cardiopulmonary exercise testing (CPET). We aimed to explore the potential association between endothelial dysfunction and the reduced CPET performance in COVID-19 survivors. METHODS: 36 consecutive COVID-19 survivors underwent symptom-limited incremental CPET and assessment of endothelium-dependent flow-mediate dilation (FMD) according to standardized protocols. RESULTS: A significantly higher FMD was documented in patients with a preserved, as compared to those with a reduced, exercise capacity (4.11% ± 2.08 vs. 2.54% ± 1.85, p = 0.048), confirmed in a multivariate analysis (ß = 0.899, p = 0.038). In the overall study population, FMD values showed a significant Pearson's correlation with two primary CPET parameters, namely ventilation/carbon dioxide production (VE/VCO2) slope (r = -0.371, p = 0.026) and end-tidal carbon dioxide tension (PETCO2) at peak (r = 0.439, p = 0.007). In multiple linear regressions, FMD was the only independent predictor of VE/VCO2 slope (ß = -1.308, p = 0.029) and peak PETCO2 values (ß = 0.779, p = 0.021). Accordingly, when stratifying our study population based on their ventilatory efficiency, patients with a ventilatory class III-IV (VE/VCO2 slope ≥ 36) exhibited significantly lower FMD values as compared to those with a ventilatory class I-II. CONCLUSIONS: The alteration of endothelial barrier properties in systemic and pulmonary circulation may represent a key pathogenic mechanism of the reduced CPET performance in COVID-19 survivors. Personalized pharmacological and rehabilitation strategies targeting endothelial function may represent an attractive therapeutic option.

Endothelial cells and blood vessels are major targets for COVID-19-induced tissue injury and spreading to various organs.

The coronavirus disease 2019 (COVID-19) infected so far over 250 million people and caused the death of over 5 million worldwide. Aging, diabetes, and cardiovascular diseases, conditions with preexisting impaired endothelial functions predispose to COVID-19. While respiratory epithelium is the main route of virus entry, the endothelial cells (ECs) lining pulmonary blood vessels are also an integral part of lung injury in COVID-19 patients. COVID-19 not only affects the lungs and respiratory system but also gastrointestinal (GI) tract, liver, pancreas, kidneys, heart, brain, and skin. Blood vessels are likely conduits for the virus dissemination to these distant organs. Importantly, ECs are also critical for vascular regeneration during injury/lesions healing and restoration of vascular network. The World Journal of Gastroenterology has published in last two years over 67 outstanding papers on COVID-19 infection with a focus on the GI tract, liver, pancreas, etc., however, the role of the endothelial and vascular components as major targets for COVID-19-induced tissue injury, spreading to various organs, and injury healing have not been sufficiently emphasized. In the present article, we focus on these subjects and on current treatments including the most recent oral drugs molnupiravir and paxlovid that show a dramatic, significant efficacy in controlling severe COVID-19 infection.

Long COVID 19 Syndrome: Is It Related to Microcirculation and Endothelial Dysfunction? Insights From TUN-EndCOV Study.

The COVID-19 disease is a multisystem disease due in part to the vascular endothelium injury. Lasting effects and long-term sequelae could persist after the infection and may be due to persistent endothelial dysfunction. Our study focused on the evaluation of endothelial quality index (EQI) by finger thermal monitoring with E4 diagnosis Polymath in a large cohort of long COVID-19 patients to determine whether long-covid 19 symptoms are associated with endothelial dysfunction. This is a cross-sectional multicenter observational study with prospective recruitment of patients. A total of 798 patients were included in this study. A total of 618 patients (77.4%) had long COVID-19 symptoms. The mean EQI was 2.02 ± 0.99 IC95% [1.95-2.08]. A total of 397 (49.7%) patients had impaired EQI. Fatigue, chest pain, and neuro-cognitive difficulties were significantly associated with endothelium dysfunction with an EQI <2 after adjustment for age, sex, diabetes, hypertension, dyslipidemia, coronary heart disease, and the severity of acute COVID-19 infection. In multivariate analysis, endothelial dysfunction (EQI <2), female gender, and severe clinical status at acute COVID-19 infection with a need for oxygen supplementation were independent risk factors of long COVID-19 syndrome. Long COVID-19 symptoms, specifically non-respiratory symptoms, are due to persistent endothelial dysfunction. These findings allow for better care of patients with long COVID-19 symptoms.