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The prevalent use of electronic cigarettes (e-cigarettes) has increased exponentially in recent years, especially in youth who are attracted to flavored e-cigarettes. Indeed, e-cigarette or vaping product use-associated lung injury (EVALI) cases started to emerge in the United States in August 2019, resulting in 2807 hospitalized cases and 68 deaths as of 18 February 2020. In the present study, we investigated, for the first time, whether flavored and nicotine containing e-cigarettes induce endothelial dysfunction to result in impaired angiogenesis and wound healing particularly under diabetic condition. Nicotine containing e-cigarettes with various contents of nicotine (0, 1.2%, 2.4%), and flavored e-cigarettes of classic tobacco, mint, menthol, and vanilla or fruit from BLU (nicotine 2.4%) or JUUL (nicotine 3%), were used to treat endothelial cells in vitro and streptozotocin-induced diabetic mice in vivo. Endothelial cell superoxide production, determined by dihydroethidium (DHE) fluorescent imaging and electron spin resonance (ESR), was markedly increased by exposure to e-cigarette extract (e-CSE) in a nicotine-content dependent manner, while nitric oxide (NO) bioavailability detected by DAF-FM fluorescent imaging was substantially decreased. All of the different flavored e-cigarettes examined also showed significant effects in increasing superoxide production while diminishing NO bioavailability. Endothelial cell apoptosis evaluated by caspase 3 activity was markedly increased by exposure to e-CSE prepared from flavored and nicotine containing e-cigarettes. Endothelial monolayer wound assays revealed that nicotine-containing and flavored e-cigarettes induced impaired angiogenic wound repair of endothelial cell monolayers. Furthermore, vascular endothelial growth factor (VEGF) stimulated wound healing in diabetic mice was impaired by exposure to e-CSEs prepared from nicotine-containing and flavored e-cigarettes. Taken together, our data demonstrate for the first time that flavored and nicotine-containing e-cigarettes induce endothelial dysfunction through excessive ROS production, resulting in decreased NO bioavailability, increased endothelial cell apoptosis, and impairment in angiogenesis and wound healing, especially under diabetic condition. These responses of endothelial dysfunction likely underlie harmful effects of e-cigarettes in endothelial-rich organs, such as heart and lungs. These data also indicate that rigorous regulation on e-cigarette use should be enforced in diabetic and/or surgical patients to avoid severe consequences from impaired angiogenesis/wound healing. [ABSTRACT FROM AUTHOR]

Over two-thirds of individuals aged 65 and older are obese or overweight in the United States. Epidemiological data show an association between the degree of adiposity and cognitive dysfunction in the elderly. In this review, the pathophysiological roles of microvascular mechanisms, including impaired endothelial function and neurovascular coupling responses, microvascular rarefaction, and blood-brain barrier disruption in the genesis of cognitive impairment in geriatric obesity are considered. The potential contribution of adipose-derived factors and fundamental cellular and molecular mechanisms of senescence to exacerbated obesity-induced cerebromicrovascular impairment and cognitive decline in aging are discussed. [ABSTRACT FROM AUTHOR]

Rationale: Sepsis is a syndrome of life-threatening organ dysfunction caused by a dysregulated host immune response to infection. Social risk factors including location and poverty are associated with sepsis-related disparities. Understanding the social and biological phenotypes linked with the incidence of sepsis is warranted to identify the most at-risk populations. We aim to examine how factors in disadvantage influence health disparities related to sepsis., Methods: A scoping review was performed for English-language articles published in the United States from 1990 to 2022 on PubMed, Web of Science, and Scopus. Of the 2064 articles found, 139 met eligibility criteria and were included for review., Results: There is consistency across the literature of disproportionately higher rates of sepsis incidence, mortality, readmissions, and associated complications, in neighborhoods with socioeconomic disadvantage and significant poverty. Chronic arterial hypertension and diabetes mellitus also occur more frequently in the same geographic distribution as sepsis, suggesting a potential shared pathophysiology., Conclusions: The distribution of chronic arterial hypertension, diabetes mellitus, social risk factors associated with socioeconomic disadvantage, and sepsis incidence, are clustered in specific geographical areas and linked by endothelial dysfunction. Such population factors can be utilized to create equitable interventions aimed at mitigating sepsis incidence and sepsis-related disparities., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to report., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: The American Heart Association updated the original recommendations for cardiovascular health (CVH) promotion, defining the Life's Essential 8 (L8)., Aim: the aim of this cross-sectional study was to compare vascular function, central hemodynamics and autonomic modulation in obese individuals with low and moderate CVH-L8., Methods: Both sexes, aged 40-70 years and Body Mass Index ≥ 30 and < 40 kg/m 2 , were submitted to anthropometric and biochemical evaluation, assessment of heart rate variability, endothelial function by flow-mediated dilatation (FMD) and central parameters by oscillometry. The CVH-L8 score was determined using the eight metrics defined in the new classification., Results: Patients (n = 82) were divided according to CVH-L8 classification: moderate group (score CVH-L8 ≥ 50 ≤ 79 points, n = 47) and low group (score CVH-L8 ≤ 49 points, n = 35). Peripheral (119 ± 10 vs 125 ± 15 mmHg, p = 0.048) and central (111 ± 10 vs 118 ± 15 mmHg; p = 0.016) systolic blood pressures and pulse wave velocity (PWV) adequacy (- 0.08 ± 0.34 vs 0.15 ± 0.42 m/s, p = 0.008) were significantly higher in low CVH-L8 group. Brachial FMD (9.24 ± 5.41 vs 6.79 ± 4.74%, p = 0.043) were lower in this same group. Only in the low CVH-L8 group low frequency/high frequency (LF/HF) ratio was significantly correlated with PWV (r = 0.338, p = 0.047) and atherogenic index of plasma with Framingham risk score (r = 0.446, p = 0.008), even after adjustment for age and sex., Conclusion: In this sample of obese individuals, low CVH-L8 was associated with higher peripheral and central blood pressures, and evidence of early vascular aging with arterial stiffness and endothelial dysfunction., (© 2022. Italian Society of Hypertension.)

Purpose of Review: Pregnancy loss (PL) has been acknowledged by the American Heart Association as a risk factor for cardiovascular diseases (CVD) later in life. This review aims to sum up recent findings (< ~ 5 years), concerning the link between PL and CVD., Recent Findings: The association between PL and risk of CVD increased with increasing number of PLs and is inversely correlated to maternal age, indicating that the association concerns euploid PLs. Likely mechanisms leading to PL and an increased risk of CVD include endothelial dysfunction, a pro-inflammatory state, antiphospholipid syndrome, autoimmunity, and genetic predisposition. PL as an independent risk factor for CVD constitutes an obvious gateway for a more targeted approach to future research, prevention, and treatment. Future research should clarify the following questions to which the answers are still unknown: whether PL is (a) directly causing the increased risk of CVD or (b) sharing pathophysiological mechanisms also leading to CVD., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The article presents a study to assess the effect of long-term modified Herbst mandibular advancement splint (MAS) treatment on obstructive sleep apnea (OSA), oxidative stress markers, and on endothelial function (EF) in the U.S. The study was conducted to 16 subjects, consisting of 11 men and 5 women, wherein 12 of whom were said to have completed an evaluation for a year. Results show that the Herbst MAS's efficacy justified the performance of larger randomized controlled trials.

Background and Aims: Recent evidence links trimethylamine oxide (TMAO) to endothelial dysfunction, an early indicator of cardiovascular disease. We aimed to determine whether short-term consumption of a diet patterned after the 2010 Dietary Guidelines for Americans (DGA) would affect endothelial function, plasma TMAO concentrations, and cardiovascular disease risk, differently than a typical American Diet (TAD)., Methods and Results: An 8-wk controlled feeding trial was conducted in overweight/obese women pre-screened for insulin resistance and/or dyslipidemia. Women were randomized to a DGA or TAD group (n = 22/group). At wk0 (pre-intervention) and wk8 (post-intervention) vascular age was calculated; endothelial function (reactive hyperemia index (RHI)) and augmentation index (AI@75) were measured using EndoPAT, and plasma TMAO was measured by LC-MS/MS. Vascular age was reduced in DGA at wk8 compared to wk0 but TAD wk8 was not different from wk0 (DGA wk0: 54.2 ± 4.0 vs. wk8: 50.5 ± 3.1 (p = 0.05), vs. TAD wk8: 47.7 ± 2.3). Plasma TMAO concentrations, RHI, and AI@75 were not different between groups or weeks., Conclusion: Consumption of a diet based on the 2010 Dietary Guidelines for Americans for 8 weeks did not improve endothelial function or reduce plasma TMAO. CLINICALTRIALS.GOV: NCT02298725., Competing Interests: Declaration of competing interest BJB had funding from the National Cattlemen's Beef Association. Work on TMAO and related analyses presented here was, however, not supported by National Cattleman's Beef Association. SHA is founder and principal of XenoMed LLC, and has consulted with Abitech Ltd.; neither activity has involved work that is related to TMAO, its related molecules, or associations of these metabolites with cardiovascular function. The other authors declare no conflict of interests. The USDA is an equal opportunity employer., (Published by Elsevier B.V.)

Diabetes mellitus (DM) is a complex metabolic disease affecting one-third of the United States population. It is characterized by hyperglycemia, where the hormone insulin is either not produced sufficiently or where there is a resistance to insulin. Patients with Type 1 DM (T1DM), in which the insulin-producing beta cells are destroyed by autoimmune mechanisms, have a significantly increased risk of developing life-threatening cardiovascular complications, even when exogenous insulin is administered. In fact, due to various factors such as limited blood glucose measurements and timing of insulin administration, only 37% of T1DM adults achieve normoglycemia. Furthermore, T1DM patients do not produce C-peptide, a cleavage product from insulin processing. C-peptide has potential therapeutic effects in vitro and in vivo on many complications of T1DM, such as peripheral neuropathy, atherosclerosis, and inflammation. Thus, delivery of C-peptide in conjunction with insulin through a pump, pancreatic islet transplantation, or genetically engineered Sertoli cells (an immune privileged cell type) may ameliorate many of the cardiovascular and vascular complications afflicting T1DM patients. [ABSTRACT FROM AUTHOR]

In the United States, latest projections indicate the number of adults 65 years of age and older is expected to double by 2050. Given that increased oxidative stress is a hallmark of aging, it is understandable that waning nitric oxide and chronic degenerative disease arise in tandem. To this end, translational evidence-based strategies are needed to mitigate the impending toll on personal and public health. Dietary nitrate supplementation, particularly in the form of beetroot juice, is an active area of inquiry that has gained considerable attention in recent years. Compelling evidence has revealed beetroot juice can elicit potent physiological responses that may offer associated health benefits for multiple clinical disorders including hypertension, dementia, and sarcopenia. Even in the absence of overt disease, age-related impairments in cardiovascular and skeletal muscle function may uniquely benefit from beetroot juice supplementation as evidence has shown blood pressure lowering effects and improved muscle function/contractility - presumably from increased nitric oxide bioavailability. This, in turn, presents a practical opportunity for susceptible populations to support ease of movement and exercise tolerance, both of which may promote free-living physical activity. A theoretical rationale details the potential health effects of dietary nitrate supplementation, wherein a working framework hypothesizes beetroot juice consumption prior to structured exercise training may offer synergistic benefits to aid healthy aging and independent-living among older adults. [ABSTRACT FROM AUTHOR]

• A high-salt diet induces hypertension, which eventually leads to cardiovascular remodeling. • High-salt induced hypertensive mice have obvious oxidative stress and endothelial dysfunction. • As a prescription that has been used in clinical practice for many years,Xin-Ji-Er-Kanghas the function of antioxidant and balance endothelin system. • XJEK mitigates cardiac remodeling in high-salt-induced hypertensive mice. Xin-Ji-Er-Kang (XJEK) is a Chinese herbal formula that has beenreported to exert effective protection against cardiovascular diseases, such as hypertension and myocarditis. The aim of the present study was to investigate the effect of XJEK on high-salt-induced hypertensive mice and its possible mechanism. The model of hypertension was established through a high-salt diet. Sixty male Kunming mice were randomized into six groups, namely the Control, Model, Low-dose XJEK, Middle-dose XJEK, High-dose XJEK and Fosinopril groups (n= 10 per group). Different steady interventions were given to each group: 0.9% Sodium chloride was added to the diet of the Control group and 8% sodium chloride to the diet of the other five groups from the very beginning. An additional 4, 8 and 12 g/kg/day XJEK were intragastrically administered to the Low-dose, Middle-dose and High-dose XJEK groups, respectively, and 2 mg/kg/day fosinopril to the fosinopril group, from the start of week 5. Systolic blood pressure (SBP) was measured weekly from weeks 1 to 8 using the tail-cuff method. At the end of week 8, left ventricular (LV) systolic pressure, LV end-diastolic pressure and rate of rise of LV pressure were examined using a TransonicScisense catheter (Transonic Systems Inc,Ithaca, NY,USA). Endothelium-dependent relaxations induced by acetylcholine were observed in an isolated thoracic aorta ring. Serum and heartsweresampled for the measurement of the following indexes:Serum nitric oxide (NO), superoxide dismutase (SOD) activity and malondialdehyde (MDA) content (determined by colorimetricanalysis); serum angiotensin II(Ang II), endothelin-1, endothelial NO synthase (eNOS), asymmetric dimethylarginine (ADMA), tetrahydrobiopterin (BH 4) concentration and l -arginine (determined by enzyme-linked immunosorbent assay); heart to body weight (HW/BW) ratio; myocardial morphological change (determined by HE and VG staining); myocardial eNOS expression (determined by immunofluorescence), and myocardial endothelin receptor A (ET A) expression (determined by western blotting). Results:Statistical data showed that the HW/BW ratio was significantly decreased in the drug treatment group. XJEK treatment could improve the heart systolic and diastolic function and ameliorate hemodynamic parameters and vascular remodeling indexes. Colorimetric results showed that, compared with the model group, XJEK increased serum SOD, NOlevels, and decreased those of serum MDA and Ang II. XJEK reverted changes in cardiac pathology, decreased the myocardial cross-sectional area, collagen volume fraction and perivascular collagen area and improved endothelial dysfunction (ED) by promoting eNOS activity, enhancing NO bioavailability, increasing the expression of BH 4 and decreasing ET A content. In addition, treatment with XJEK decreased ADMA content in the myocardium. Conclusion:In conclusion, XJEK mitigates cardiac remodeling in high-salt-induced hypertensive mice. The potential mechanism involves improved oxidative stress and endothelial dysfunction, independently of ameliorating BP. [ABSTRACT FROM AUTHOR]

Background: The incidence of traumatic brain injuries (TBIs) is on the rise in the USA. Concussions, or mild TBIs without skull fracture, account for about 75% of all TBIs. Mild TBIs (mTBIs) lead to memory and cognitive deficits, headaches, intraocular pressure rises, axonal degeneration, neuroinflammation, and an array of cerebrovascular dysfunctions, including increased vascular permeability and decreased cerebral blood flow. It has been recently reported that besides vascular dysfunction in the cerebral circulation, mTBI may also cause a significant impairment of endothelial function in the systemic circulation, at least within mesenteric microvessels. In this study, we investigated whether mTBI affects endothelial function in aortas and determined the contribution of transient receptor potential canonical (TRPC) channels to modulating mTBI-associated endothelial dysfunction.Methods: We used a model of closed-head mTBI in C57BL/6, 129S, 129S-C57BL/6-F2 mice, and 129S-TRPC1 and 129S-C57BL/6-TRPC6 knockout mice to determine the effect of mTBI on endothelial function in mouse aortas employing ex vivo isometric tension measurements. Aortic tissue was also analyzed using immunofluorescence and qRT-PCR for TRPC6 expression following mTBI.Results: We show that in various strains of mice, mTBI induces a pronounced and long-lasting endothelial dysfunction in the aorta. Ablation of TRPC6 protects mice from mTBI-associated aortic endothelial dysfunction, while TRPC1 ablation does not impact brain injury-induced endothelial impairment in the aorta. Consistent with a role of TRPC6 activation following mTBI, we observed improved endothelial function in wild type control mice subjected to mTBI following 7-day in vivo treatment with larixyl acetate, an inhibitor of TRPC6 channels. Conversely, in vitro treatment with the pro-inflammatory endotoxin lipopolysaccharide, which activates endothelial TRPC6 in a Toll-like receptor type 4 (TLR4)-dependent manner, worsened aortic endothelial dysfunction in wild type mice. Lipopolysaccharide treatment in vitro failed to elicit endothelial dysfunction in TRPC6 knockout mice. No change in endothelial TRPC6 expression was observed 7 days following TBI.Conclusions: These data suggest that TRPC6 activation may be critical for inducing endothelial dysfunction following closed-head mTBI and that pharmacological inhibition of the channel may be a feasible therapeutic strategy for preventing mTBI-associated systemic endothelial dysfunction. [ABSTRACT FROM AUTHOR]

Rationale: Impaired lung function is a potent independent predictor of coronary artery disease (CAD) in individuals without human immunodeficiency virus (HIV) infection; however, the relationship between lung function and CAD in HIV remains undefined. Objectives: To examine the relationship between lung function, CAD, mortality, and circulating biomarkers in HIV. Methods: Spirometry, diffusing capacity of the lung for carbon monoxide (Dl CO ), emphysema, coronary artery calcium, mortality, cause of death, and biomarkers were examined in HIV-infected and uninfected individuals enrolled in a cohort study at the University of Pittsburgh. Results were then validated in the Multicenter AIDS Cohort Study (MACS) cohort. Results: We examined data on 234 participants in the Pittsburgh cohort. The mean ± standard deviation age was 49.5 ± 10.2 years old, 82.1% were male, and 67.5% were ever smokers. Among the 177 of 234 individuals with HIV infection, lower Dl CO (not forced expiratory volume in 1 second or emphysema) was independently associated with greater coronary artery calcium (odds ratio, 1.43 per 10% lower Dl CO ; 95% confidence interval, 1.14-1.81). HIV-infected individuals with both reduced Dl CO and coronary artery calcium had a much higher mortality than those with either low Dl CO or coronary calcium alone or with neither condition. Endothelin-1, a circulating biomarker of endothelial dysfunction, was associated with both lower Dl CO and greater coronary artery calcium in those with HIV infection. Results were reproducible in 144 individuals enrolled in the MACS cohort; intercellular adhesion molecule 1 was the biomarker of endothelial dysfunction assessed in the MACS cohort. Conclusions: Impaired Dl CO and CAD were associated with each other and with higher mortality in individuals with HIV infection.

Background: African Americans have been reported to have a higher prevalence of Alzheimer's disease (AD) than Caucasians, but etiology-specific AD biomarkers have not been systematically analyzed in older African Americans. Coexisting cerebrovascular disease may also contribute to this increased prevalence. We hypothesized that cerebrospinal fluid (CSF) biomarkers of amyloid, neurodegeneration, and endothelial dysfunction would differ between older African Americans and Caucasians with normal cognition and cognitive impairment associated with AD., Methods: We prospectively recruited 135 older Americans to undergo detailed clinical, neuropsychological, genetic, magnetic resonance imaging (MRI), and CSF analysis from 2013 to 2015 at Emory University (Atlanta, GA, USA). We compared levels of CSF markers for β-amyloid (Aβ42, Aβ40), total and phosphorylated tau (t-tau and p-tau 181 , respectively), endothelial dysfunction (soluble vascular cell adhesion molecule 1, soluble intercellular adhesion molecule 1), α-synuclein, and neurodegeneration (neurofilament light chain [NfL]), as well as MRI markers, for hippocampal atrophy and cerebrovascular disease (white matter hyperintensity [WMH] volume)., Results: Sixty-five older African Americans (average age, 69.1 years) and 70 older Caucasians (average age, 70.8 years) were included. After adjusting for demographic variables, AD risk alleles, and cognitive function, older African Americans had lower CSF levels of p-tau 181 (difference of 7.4 pg/ml; 95% CI, 3.7-11.2 pg/ml; p < 0.001), t-tau (difference of 23.6 pg/ml; 95% CI, 9.5-37.7; p = 0.001), and Aβ40 (difference of 1.35 ng/ml; 95% CI, 0.29-2.42 ng/ml; p = 0.013) despite similar levels of Aβ42, NfL, WMH volume, and hippocampal volume. Cognitively impaired African Americans also had lower CSF t-tau/Aβ42 (difference of 0.255 per 1-SD change in composite cognition; 95% CI, 0.100-0.409; p = 0.001) and p-tau 181 /Aβ42 (difference of 0.076 per 1-SD change in composite cognition; 95% CI, 0.031-0.122; p = 0.001). These could not be explained by measured biomarkers of non-AD processes, but African Americans may be more susceptible than Caucasians to the cognitive effects of WMH., Conclusions: Despite comparable levels of CSF Aβ42 and Aβ42/Aβ40, cognitive impairment in African Americans is associated with smaller changes in CSF tau markers but greater impact from similar WMH burden than Caucasians. Race-associated differences in CSF tau markers and ratios may lead to underdiagnosis of AD in African Americans., Trial Registration: ClinicalTrials.gov, NCT02089555 . Retrospectively registered on 14 March 2014.