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Introduction: Endothelial function is significantly impaired in patients with SLE compared to healthy controls. Elevated activation of the mammalian target of rapamycin complex 1 (mTORC1) is reported in humans and mice with SLE. However, it is unclear if elevated mTORC1 in SLE contributes to impaired mitophagy and endothelial dysfunction. Therefore, we tested the hypothesis that inhibiting mTORC1 with rapamycin would increase mitophagy and attenuate endothelial dysfunction and inflammatory responses in SLE. Methods: Nine-week-old female lupus-prone (MRL/lpr) and healthy control (MRL/MpJ) mice were randomly assigned into rapamycin treatment (lpr_Rapamycin and MpJ_Rapamycin) or control (lpr_Control and MpJ_Control) groups. Rapamycin was injected i.p. 3 days per week for 8 weeks. After 8 weeks, endothelium-dependent vasorelaxation to acetylcholine (ACh) and endothelium-independent vasorelaxation to sodium nitroprusside (SNP) were measured in thoracic aortas using a wire myograph. Results: MTORC1 activity was increased in aorta from lpr mice as demonstrated by increased phosphorylation of s6rp and p70s6k and significantly inhibited by rapamycin (s6rp, p < 0.0001, p70s6k, p = 0.04, respectively). Maximal responses to Ach were significantly impaired in lpr_Control (51.7% ± 6.6%) compared to MpJ_Control (86.7% ± 3.6%) (p < 0.0001). Rapamycin prevented endothelial dysfunction in the thoracic aorta from lupus mice (lpr_Rapamycin) (79.6% ± 4.2%) compared to lpr_Control (p = 0.002). Maximal responses to SNP were not different across groups. Phosphorylation of endothelial nitric oxide synthase also was 42% lower in lpr_Control than MpJ_Control and 46% higher in lpr_Rapamycin than lpr_Control. The inflammatory marker, vascular cell adhesion protein 1 (Vcam 1), was elevated in aorta from lupus mice compared with healthy mice (p = 0.001), and significantly reduced with Rapamycin treatment (p = 0.0021). Mitophagy markers were higher in lupus mice and reduced by rapamycin treatment, suggesting altered mitophagy in lpr mice. Conclusion: Collectively, these results demonstrate the beneficial effects of inhibiting mTORC1 on endothelial function in SLE mice and suggest inflammation and altered mitophagy contribute to endothelial dysfunction in SLE.

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The regulation of vascular tone by perivascular tissues is a complex interplay of various paracrine factors. Here, we investigate the anti-contractile effect of skeletal muscle surrounding the femoral and carotid arteries and its underlying mechanisms. Using male and female Wistar rats, we demonstrated that serotonin, phenylephrine, and U-46619 induced a concentration-dependent vasoconstrictor response in femoral artery rings. Interestingly, this response was diminished in the presence of surrounding femoral skeletal muscle, irrespective of sex. No anti-contractile effect was observed when the carotid artery was exposed to its surrounding skeletal muscle. The observed effect in the femoral artery persisted even in the absence of endothelium and when the muscle was detached from the artery. Furthermore, the skeletal muscle surrounding the femoral artery was able to promote an anti-contractile effect in three other vascular beds (basilar, mesenteric, and carotid arteries). Using inhibitors of lactate dehydrogenase and the 1/4 monocarboxylate transporter, we confirmed the involvement of lactate, as both inhibitors were able to abolish the anti-contractile effect. However, lactate did not directly promote vasodilation; rather, it exerted its effect by activating 5' AMP-activated protein kinase (AMPK) and neuronal nitric oxide synthase (NOS1) in the skeletal muscle. Accordingly, Nω-propyl L-arginine, a specific inhibitor of NOS1, prevented the anti-contractile effect, as well as lactate-induced phosphorylation of NOS1 at the stimulatory serine site (1417) in primary skeletal muscle cells. Phosphorylation of NOS1 was reduced in the presence of Bay-3827, a selective AMPK inhibitor. In conclusion, femoral artery-associated skeletal muscle is a potent paracrine and endocrine organ that influences vascular tone in both sexes. Mechanistically, the anti-contractile effect involves muscle fiber type and/or its anatomical location but not the type of artery or its related vascular endothelium. Finally, the femoral artery anti-contractile effect is mediated by the lactate-AMPK-phospho-NOS1Ser1417-NO signaling axis.

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Objective.Peripheral Artery Disease (PAD) is a progressive cardiovascular condition affecting 8-10 million adults in the United States. PAD elevates the risk of cardiovascular events, but up to 50% of people with PAD are asymptomatic and undiagnosed. In this study, we tested the ability of a device, REFLO (Rapid Electromagnetic FLOw), to identify low blood flow using electromagnetic radiation and dynamic thermography toward a non-invasive PAD diagnostic.Approach.During REFLO radio frequency (RF) irradiation, the rate of temperature increase is a function of the rate of energy absorption and blood flow to the irradiated tissue. For a given rate of RF energy absorption, a slow rate of temperature increase implies a large blood flow rate to the tissue. This is due to the cooling effect of the blood. Post-irradiation, a slow rate of temperature decrease is associated with a low rate of blood flow to the tissue. Here, we performed two cohorts of controlled flow experiments on human calves during baseline, occluded, and post-occluded conditions. Nonlinear regression was used to fit temperature data and obtain the rate constant, which was used as a metric for blood flow.Main results.In the pilot study, (N= 7) REFLO distinguished between baseline and post-occlusion during the irradiation phase, and between baseline and occlusion in the post-irradiation phase. In the reliability study, (N= 5 with 3 visits each), two-way ANOVA revealed that flow and subject significantly affected skin heating and cooling rates, while visit did not.Significance.Results suggest that MMW irradiation can be used to distinguish between blood flow rates in humans. Utilizing the rate of skin cooling rather than heating is more consistent for distinguishing flow. Future modifications and clinical testing will aim to improve REFLO's ability to distinguish between flow rates and evaluate its ability to accurately identify PAD.

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The evidence on the impact of fruits and vegetable types on cardiovascular risk factors remains limited. Specifically, the utilisation of biomarkers to objectively measure dietary compliance and metabolic responses is emerging. This protocol and baseline characteristics of a pilot randomised controlled, crossover, dietary intervention study aimed to examine the effects of citrus fruits, cruciferous vegetables, or common fruits and vegetables on cardiovascular risk factors. A total of 39 volunteers with untreated prehypertension was recruited and consumed a standardised, provided diet with eight daily portions of citrus fruits and cruciferous vegetables, common fruits and vegetables, or a low fruit and vegetable diet (two portions/d, control diet) in a random order for 2 weeks each, separated by a wash-out week. A targeted cohort-based recruitment strategy was utilised and resulted in 74% of participants recruited by re-contacting preselected individuals from two cohort studies with a 15% average enrolment rate. Participants had an average age of 54.4 years (±6.1 years), BMI of 27.9 kg/m2, and BP of 135/81 mmHg and were mainly male (67%). The primary outcome was office blood pressure; secondary outcomes included arterial stiffness, lipid profiles, inflammation, cognitive function, and subjective mood. Biofluids, i.e., 24 h urine, stool, and blood samples, were collected for biomarker measurements with multiple metabolomic platforms and the gut microbial composition, together with traditional dietary biomarkers.

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OBJECTIVES: The objectives of the study were first, to compare different markers of maternal vascular function in women with gestational diabetes mellitus (GDM), preeclampsia (PE), or gestational hypertension (GH) and women whose pregnancies were unaffected by these complications. Second, to assess the association between maternal vascular function and markers of placental perfusion, maternal vascular - placental axis, in these four groups of women. STUDY DESIGN: This was a prospective observational study of women attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation at King's College Hospital, London, UK. This visit included recording of maternal demographic characteristics and medical history, ultrasound examination for fetal anatomy and growth, Doppler studies of the uterine arteries and ophthalmic arteries, carotid-femoral pulse-wave velocity (PWV) measurements, estimation of augmentation index (AIx) and total peripheral resistance and measurements of serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFLT-1). Linear regression was performed for the outcomes of uterine artery pulsatility index (UtA-PI) multiples of median (MoM), PLGF MoM and sFLT-1 MoM. Ophthalmic artery peak systolic velocity (PSV) ratio, PWV , AIx and total peripheral vascular resistance were assessed as potential predictors. This analysis was carried out in all women and separately in the different groups. RESULTS: The study population of 6502 women included 614 (9.4%) with GDM, 140 (2.1%) who subsequently developed PE and 129 (2.0%) who developed GH. Women with GDM, compared to those with pregnancies unaffected by GDM, PE or GH, had increased PWV. Women with PE or GH, compared to those with unaffected pregnancies, had lower PlGF MoM and higher UtA-PI MoM, sFLT1 MoM, AIx, PWV, total peripheral resistance and ophthalmic artery PSV ratio. In unaffected pregnancies, ophthalmic artery PSV ratio was predictive of UtA-PI MoM, and ophthalmic artery PSV ratio, AIx, total peripheral resistance, and PWV were predictive of PLGF MoM and sFLT-1 MoM. In women with GDM, ophthalmic artery PSV ratio was predictive of UtA-PI MoM and ophthalmic artery PSV ratio, total peripheral resistance, and PWV were predictive of PLGF MoM, and total peripheral resistance was predictive of sFLT-1 MoM. In women with PE, ophthalmic artery PSV ratio was predictive of UtA-PI MoM, PLGF MoM and sFLT-1 MoM. In women unaffected by GDM, PE or GH, ophthalmic artery PSV ratio was predictive of UtA-PI MoM and AIx, total peripheral resistance, PWV and ophthalmic artery PSV ratio were predictive of PLGF MoM and sFLT-1 MoM. CONCLUSIONS: In the third trimester of pregnancy, women with PE, GH, and GDM present with increased arterial stiffness. In addition, those diagnosed with hypertensive complications show increased peripheral vascular resistance. Ophthalmic artery PSV ratio provides predictive information for placental perfusion and function for all pregnant women, whereas vascular indices are more informative for placental function in women with unaffected pregnancy and those with GDM, than in those with PE or GH. These data suggest that vascular assessment in women during pregnancy may not only provide information about maternal vascular health but can be used to offer information about individual risk for development of placental insufficiency. The selection of vascular index will have to be tailored according to maternal profile and pregnancy complication.

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Chronic Obstructive Pulmonary Disease (COPD) exerts a severe toll on human health and the economy, with high prevalence and mortality rates. The search for bioactive components effective in the treatment of COPD has become a focal point of research. Beetroot juice, readily accessible and cost-effective, is noted for its ability to enhance athletic performance and for its preventive and therapeutic impact on hypertension. Beetroot juice is a rich source of dietary nitrates and modulates physiological processes via the nitrate-nitrite- nitric oxide pathway, exerting multiple beneficial effects such as antihypertensive, bronchodilatory, anti-inflammatory, antioxidant, hypoglycemic, and lipid-lowering actions. This paper provides a review of the existing research on the effects of beetroot juice on COPD, summarizing its potential in enhancing exercise capacity, lowering blood pressure, improving vascular function, and ameliorating sleep quality among patients with COPD. The review serves as a reference for the prospective use of beetroot juice in the symptomatic improvement of COPD, as well as in the prevention of exacerbations and associated comorbidities.

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Hypogonadism is a risk factor for cardiovascular disease (CVD) in men related, in part, to increased oxidative stress. Elevated large artery stiffness and central pulsatile hemodynamics (e.g., pulse pressure and wave reflection magnitude) are independent risk factors for CVD. However, whether large artery stiffness and central pulsatile hemodynamics are (1) elevated in hypogonadal men independent of traditional CVD risk factors and (2) related to increased oxidative stress is unknown. Young men (N = 23; 30 ± 4 years) and middle-aged/older (MA/O) men with normal (> 400-1000 ng/dL; n = 57; 59 ± 7 years) or low testosterone (< 300 ng/dL; n = 21; 59 ± 7 years) underwent assessments of large artery stiffness (carotid ß-stiffness via ultrasonography) and central pulsatile hemodynamics (pulse wave analysis; SphygmoCor XCEL) following an infusion of saline or vitamin C to test the tonic suppression of vascular function by oxidative stress. Carotid stiffness differed by age (p < 0.001) and gonadal status within MA/O men (low testosterone vs. normal testosterone: 9.3 ± 0.7 vs. 8.0 ± 0.3U, p = 0.036). Central pulsatile hemodynamics did not differ by age or gonadal status (p > 0.119). Vitamin C did not alter carotid stiffness in any group (p > 0.171). There was a significant group × infusion interaction on aortic reflection magnitude (p = 0.015). Vitamin C treatment reduced aortic reflection magnitude in young and MA/O men with normal testosterone (both p < 0.001) but not MA/O men with low testosterone (p = 0.891). Collectively, hypogonadism may accelerate age-related large artery stiffening in MA/O men with low testosterone, independent of CVD risk factors; however, this is not related to increased reactive oxygen species sensitive to an acute vitamin C infusion.

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BACKGROUND: Historical exclusion of females in research has been, in part, due to the perceived influence of natural menstrual (NAT) and oral contraceptive pill (OCP) cycles on vascular outcomes. NAT and OCP cycle phases may influence brachial artery (BA) endothelial function, however, findings are mixed. Minimal research has examined arterial stiffness, smooth muscle and lower limb endothelial function. The purpose of this study was to investigate the influence of NAT and OCP cycles on cardiovascular outcomes and cellular regulation. METHODS: Forty-nine premenopausal females (n=17 NAT, n=17 2nd generation OCP, n=15 3rd generation OCP) participated in two randomized order visits in the low (LH: early follicular/placebo) and high (HH: mid-luteal/active) hormone cycle phases. BA and femoral artery (SFA) endothelial function [flow-mediated dilation (FMD) test], smooth muscle function (nitroglycerine-mediated dilation test) and carotid and peripheral (pulse wave velocity) arterial stiffness were assessed. Cultured female human endothelial cells were exposed to participant serum for 24h to examine endothelial nitric oxide synthase (eNOS) and estrogen receptor alpha (ERα) protein content. RESULTS: BA FMD was elevated in the HH versus LH phase, regardless of group (HH:7.7±3.5%, LH:7.0±3.3%, p=0.02); however, allometric scaling for baseline diameter resulted in no phase effect (HH:7.6±2.6%, LH:7.1±2.6%, p=0.052, d=0.35). SFA FMD, BA and SFA smooth muscle function, arterial stiffness, and eNOS and ERα protein content were unaffected. CONCLUSIONS: NAT and OCP phases examined have minimal influence on vascular outcomes and ERα-eNOS pathway, apart from a small effect on BA endothelial function partially explained by differences in baseline artery diameter.

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Background: The impact of singing on cardiovascular health has not been extensively studied. The aim of this study is to investigate the effect of singing on cardiovascular biomarkers in an aging population with coronary artery disease. Methods: Participants had three study visits separated by 2-7 days, according to a randomized, single-blind, cross-over, controlled design: (1) a 30-minute period of coached singing from an in-person music therapist, (2) a 30-minute period of singing along to an instructional video and (3) a 30-minute rest (control). Primary outcomes included macrovascular endothelial function assessed by brachial artery flow-mediated dilation and microvascular function assessed by peripheral arterial tonometry (Framingham reactive hyperemia index; fRHI). Heart rate variability was a secondary outcome. Results: Sixty-five subjects (mean age 67.7± 0.8, 40% women) completed the study. Compared to control, there was an increase in fRHI for the singing video intervention (estimate 0.54, SE 0.25, p=0.005) but not for the coaching intervention (estimate 0.11, SE 0.18, p=0.570). There was no change in macrovascular function with either intervention. The low frequency/high frequency (LF/HF) ratio increased by 2.80 (SE 1.03, p=0.008), and the LnHF power decreased by -0.90 ms2 (SE 0.29, p=0.003) with the video (during to pre-change). When assessing post- to pre- change, the coaching intervention showed a significant change of -0.62 ms2 (SE 0.29, p=0.036) in LnHF power. Conclusions: Singing along to an instructional video for 30 minutes improved microvascular, but not macrovascular, endothelial function, in older patients with CAD. HRV changes with singing are similar to that of exercise. Clinical trial registration: ClinicalTrials.gov, identifier: NCT04121741.

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BACKGROUND AND AIMS: We investigated circulating homocysteine (Hcy), a cardiovascular disease (CVD) risk factor, examining its dietary associations to provide personalized nutrition advice. This study addressed the inadequacy of current dietary interventions to ultimately address the disproportionately high incidence of CVD in Black populations. METHODS AND RESULTS: Cross-sectional analyses of 1,867 Black individuals of the PURE-SA study allowed the identification of dietary intake and cardiovascular measure interactions on three sub-categories: (1) normal blood pressure (BP), hypertension or Hcy-related hypertension (H-type), (2) low, normal or high Hcy concentrations, and (3) Hcy-related genetic combinations. Favorable body composition, but adverse dietary intake and cardiovascular determinants, were observed in higher Hcy categories. H-types, compared to regular hypertensives, had higher alcohol and lower macronutrient and micronutrient consumption. Inverse associations with carotid-radial pulse wave velocity were evident between monounsaturated fatty acid (FA) consumption and H-type hypertension as well as polyunsaturated FA and CBS883/ins68 TT carriers. Energy intake was positively associated with vascular cell adhesion molecule-1 (VCAM-1) in variant CBST883C/ins68 and CBS9276 GG carriers. VCAM-1 was also positively associated with plant protein intake in CBS9276 GG and MTR2756 AA carriers and negatively with total protein intake and CBS9276 GG carriers. Alcohol intake was positively associated with intercellular adhesion molecule-1 in MTR2756 minor allele carriers. CONCLUSION: Because Hcy gene-diet interactions are evident, personalized nutrition, by adjusting diets based on genetic profiles (e.g., CBS and MTR variations) and dietary interactions (e.g., FAs and proteins), can enhance cardiovascular outcomes by managing Hcy and related hypertension in genetically susceptible individuals.

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Our recent findings revealed that human adipose tissues (AT)-derived extracellular vesicles (adiposomes) vary in cargo among obese and lean individuals. The main objective of this study was to investigate the adiposomal lipid profiles and their correlation with cardiometabolic risk factors. AT samples were collected from obese subjects and lean controls and analyzed for their characteristics and lipid content. In addition, we measured the correlation between adiposomal lipid profiles and body composition, glucose and lipid metabolic profiles, brachial artery vasoreactivity, AT arteriolar flow-induced dilation, and circulating markers such as IL-6, C-reactive protein, and nitric oxide (NO). Compared to lean controls, adiposomes isolated from obese subjects were higher in number after normalization to AT volume. The two major lipid classes differentially expressed were lysophosphatidylcholine/phosphatidylcholine (LPC/PC) and ceramides (Cer). All lipids in the LPC/PC class were several-fold lower in adiposomes from obese subjects compared to lean controls, on top of which were PC 18:2, PC 18:1, and PC 36:3. Most ceramides were markedly upregulated in the obese group, especially Cer d37:0, Cer d18:0, and Cer d39:0. Regression analyses revealed associations between adiposomal lipid profiles and several cardiometabolic risk factors such as body mass index (BMI), fat percentage, insulin resistance, arteriolar and brachial artery vasoreactivity, NO bioavailability, and high-density lipoproteins (HDL-C). We conclude that the ability of adiposomes from obese subjects to disrupt cardiometabolic function could be partly attributed to the dysregulated lipid cargo.

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Chronic kidney disease (CKD) increases the risk of cardiovascular disease and cognitive impairment. Curcumin is a polyphenol that improves vascular and cognitive function in older adults; however, its effects on vascular and cognitive function in patients with CKD are unknown. We hypothesized that curcumin supplementation would improve vascular and cognitive function in patients with CKD. Eighty-eight adults diagnosed with stage 3b or 4 CKD (aged 66 ± 8 years, 75% male) participated in a 12-month, randomized, double-blind, placebo-controlled study to test the effects of curcumin (Longvida®, 2000 mg/day) on vascular and cognitive function. Our primary outcome was brachial artery flow-mediated dilation (FMD). Our secondary outcomes were nitroglycerin-mediated dilation, carotid-femoral pulse wave velocity (cfPWV), and cognitive function assessed via the NIH Toolbox Cognition Battery. At baseline, the mean estimated glomerular filtration rate was 34.7 ± 10.8, and the median albumin/creatinine ratio was 81.9 (9.7, 417.3). A total of 44% of participants had diabetes. Compared with placebo, 12 months of curcumin did not improve FMD (median change from baseline was -0.7 (-2.1, 1.1) and -0.1 (-1.5, 1.5) for curcumin and placebo, respectively, with p = 0.69). Similarly, there were no changes in nitroglycerin-mediated dilation, cfPWV, or cognitive outcomes. These results do not support chronic curcumin supplementation to improve vascular and cognitive function in patients with CKD.

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Maintaining endothelial cell (EC) and vascular smooth muscle cell (VSMC) integrity is an important component of human health and disease because both EC and VSMC regulate various functions, including vascular tone control, cellular adhesion, homeostasis and thrombosis regulation, proliferation, and vascular inflammation. Diverse stressors affect functions in both ECs and VSMCs and abnormalities of functions in these cells play a crucial role in cardiovascular disease initiation and progression. Toll-like receptors (TLRs) are important detectors of pathogen-associated molecular patterns derived from various microbes and viruses as well as damage-associated molecular patterns derived from damaged cells and perform innate immune responses. Among TLRs, several studies reveal that TLR3 plays a key role in initiation, development and/or protection of diseases, and an emerging body of evidence indicates that TLR3 presents components of the vasculature, including ECs and VSMCs, and plays a functional role. An agonist of TLR3, polyinosinic-polycytidylic acid [poly (I:C)], affects ECs, including cell death, inflammation, chemoattractant, adhesion, permeability, and hemostasis. Poly (I:C) also affects VSMCs including inflammation, proliferation, and modulation of vascular tone. Moreover, alterations of vascular function induced by certain molecules and/or interventions are exerted through TLR3 signaling. Hence, we present the association between TLR3 and vascular function according to the latest studies.

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BACKGROUND: As key regulators of gene expression, microRNAs affect many cardiovascular mechanisms and have been associated with several cardiovascular diseases. In this study, we aimed to investigate the relation of whole blood microRNAs with several quantitative measurements of vascular function, and explore their biological role through an integrative microRNA-gene expression analysis. METHODS: Peripheral whole blood microRNA expression was assessed through RNA-Seq in 2606 participants (45.8% men, mean age: 53.93, age range: 30 to 95 years) from the Rhineland Study, an ongoing population-based cohort study in Bonn, Germany. Weighted gene co-expression network analysis was used to cluster microRNAs with highly correlated expression levels into 14 modules. Through linear regression models, we investigated the association between each module's expression and quantitative markers of vascular health, including pulse wave velocity, total arterial compliance index, cardiac index, stroke index, systemic vascular resistance index, reactive skin hyperemia and white matter hyperintensity burden. For each module associated with at least one trait, one or more hub-microRNAs driving the association were defined. Hub-microRNAs were further characterized through mapping to putative target genes followed by gene ontology pathway analysis. RESULTS: Four modules, represented by hub-microRNAs miR-320 family, miR-378 family, miR-3605-3p, miR-6747-3p, miR-6786-3p, and miR-330-5p, were associated with total arterial compliance index. Importantly, the miR-320 family module was also associated with white matter hyperintensity burden, an effect partially mediated through arterial compliance. Furthermore, hub-microRNA miR-192-5p was related to cardiac index. Functional analysis corroborated the relevance of the identified microRNAs for vascular function by revealing, among others, enrichment for pathways involved in blood vessel morphogenesis and development, angiogenesis, telomere organization and maintenance, and insulin secretion. CONCLUSIONS: We identified several microRNAs robustly associated with cardiovascular function, especially arterial compliance and cardiac output. Moreover, our results highlight miR-320 as a regulator of cerebrovascular damage, partly through modulation of vascular function. As many of these microRNAs were involved in biological processes related to vasculature development and aging, our results contribute to the understanding of vascular physiology and provide putative targets for cardiovascular disease prevention.

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Background: As women age, especially after menopause, cardiovascular disease (CVD) prevalence rises, posing a significant global health concern. Regular exercise can mitigate CVD risks by improving blood pressure and lipid levels in postmenopausal women. Yet, the optimal exercise modality for enhancing vascular structure and function in this demographic remains uncertain. This study aims to compare five exercise forms to discern the most effective interventions for reducing cardiovascular risk in postmenopausal women. Methods: The study searched PubMed, Web of Science, Cochrane, EBSCO, and Embase databases. It conducted a network meta-analysis (NMA) of randomized controlled trials (RCTs) on five exercise interventions: continuous endurance training (CET), interval training (INT), resistance training (RT), aerobic combined with resistance training (CT), and hybrid-type training (HYB). Outcome measures included carotid artery intima-media thickness (IMT), nitric oxide (NO), augmentation index (AIx), pulse wave velocity (PWV), and flow-mediated dilatation (FMD) of the brachial artery. Eligible studies were assessed for bias using the Cochrane tool. A frequentist random-effects NMA was employed to rank exercise effects, calculating standardized mean differences (SMDs) with 95% confidence intervals (CIs). Results: The analysis of 32 studies (n = 1,427) indicates significant increases in FMD with CET, INT, RT, and HYB in postmenopausal women. Reductions in PWV were significant with CET, INT, RT, CT, and HYB. AIx decreased significantly with INT and HYB. CET, INT, and CT significantly increased NO levels. However, no significant reduction in IMT was observed. SUCRA probabilities show INT as most effective for increasing FMD, CT for reducing PWV, INT for decreasing AIx, CT for lowering IMT, and INT for increasing NO in postmenopausal women. Conclusion: The study demonstrates that CET, INT, RT, and HYB have a significant positive impact on FMD in postmenopausal women. Furthermore, all five forms of exercise significantly enhance PWV in this population. INT and HYB were found to have a significant positive effect on AIx in postmenopausal women, while CET, INT, and CT were found to significantly improve NO levels. For improving vascular function in postmenopausal women, it is recommended to prioritize INT and CT exercise modalities. On the other hand, as CET and RT were not ranked at the top of the Sucra value ranking in this study and were less effective than INT and CT as exercise interventions to improve vascular function in postmenopausal women, it is not recommended that CET and RT be considered the preferred exercise modality.

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The increasing prevalence of type 2 diabetes mellitus (T2DM) is a significant worldwide health concern caused by sedentary lifestyles and unhealthy diets. Beyond glycemic control, T2DM impacts multiple organ systems, leading to various complications. While traditionally associated with cardiovascular and microvascular complications, emerging evidence indicates significant effects on pulmonary health. Pulmonary vascular dysfunction and fibrosis, characterized by alterations in vascular tone and excessive extracellular matrix deposition, are increasingly recognized in individuals with T2DM. The onset of T2DM is often preceded by prediabetes, an intermediate hyperglycemic state that is associated with increased diabetes and cardiovascular disease risk. This review explores the relationship between T2DM, pulmonary vascular dysfunction and pulmonary fibrosis, with a focus on potential links with prediabetes. Pulmonary vascular function, including the roles of nitric oxide (NO), prostacyclin (PGI2), endothelin-1 (ET-1), thromboxane A2 (TxA2) and thrombospondin-1 (THBS1), is discussed in the context of T2DM and prediabetes. Mechanisms linking T2DM to pulmonary fibrosis, such as oxidative stress, dysregulated fibrotic signaling, and chronic inflammation, are explained. The impact of prediabetes on pulmonary health, including endothelial dysfunction, oxidative stress, and dysregulated vasoactive mediators, is highlighted. Early detection and intervention during the prediabetic stage may reduce respiratory complications associated with T2DM, emphasizing the importance of management strategies targeting blood glucose regulation and vascular health. More research that looks into the mechanisms underlying pulmonary complications in T2DM and prediabetes is needed.

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BACKGROUND: Mobility limitations (e.g., using wheelchair) have been closely linked to diminished functional independence and quality of life in older adults. The regulation of mobility is pertaining to multiple neurophysiologic and sociodemographic factors. We here aimed to characterize the relationships of these factors to the risk of restricted mobility in older adults. METHODS: In this longitudinal study, 668 older adults with intact mobility at baseline completed the baseline assessments of clinical characteristics, cognitive function, sleep quality, activities of daily living (ADL), walking performance, beat-to-beat blood pressure, and structural MRI of the brain. Then 506 of them (mean age = 70.7 ± 7.5 years) responded to the follow-up interview on the mobility limitation (as defined by if using wheelchair, cane, or walkers, or being disabled and lying on the bed) after 18 ± 3.5 months. Logistic regression analyses were performed to examine the relationships between the baseline characteristics and the follow-up mobility restriction. RESULTS: At baseline, compared to intact-mobility group (n = 475), restricted-mobility group (n = 31) were older, with lower score of ADL and the Montreal Cognitive Assessment (MoCA), greater score of Pittsburgh Sleep Quality Index (PSQI), poorer cardio- and cerebral vascular function, and slower walking speeds (ps < 0.05). The logistic regression analysis demonstrated that participants who were with history of falls, uncontrolled-hypertension, and/or greater Fazekas scale (odds ratios (ORs):1.3 ~ 13.9, 95% confidence intervals (CIs) = 1.1 ~ 328.2), walked slower, and/or with lower ADL score (ORs: 0.0026 ~ 0.9; 95%CI: 0.0001 ~ 0.99) at baseline, would have significantly greater risk of restricted mobility (p < 0.05; VIFs = 1.2 ~ 1.9). CONCLUSIONS: These findings provide novel profile of potential risk factors, including vascular characteristics, psycho-cognitive and motor performance, for the development of restricted mobility in near future in older adults, ultimately helping the design of appropriate clinical and rehabilitative programs for mobility in this population.

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The purpose of this study was to examine the effects of 6 weeks of localized, muscle-focused (quadriceps femoris) passive heat therapy (PHT) on resistance artery function, exercise haemodynamics and exercise performance relative to knee extension (KE) exercise training (EX). We randomized 34 healthy adults (ages 18-36; n = 17 female, 17 male) to receive either PHT or sham heating sessions (120 min, 3 days/week), or EX (40 min, 3 days/week) over 6 weeks. Blood flow was assessed with Doppler ultrasound of the femoral artery during both passive leg movement (PLM) and a KE graded exercise test. Muscle biopsies were taken from the vastus lateralis at baseline and after 6 weeks. Peak blood flow during PLM increased to the same extent in both the EX (∼10.5% increase, P = 0.009) and PHT groups (∼8.5% increase, P = 0.044). Peak flow during knee extension exercise increased in EX (∼19%, P = 0.005), but did not change in PHT (P = 0.523) and decreased in SHAM (∼7%, P = 0.020). Peak vascular conductance during KE increased by ∼25% in EX (P = 0.030) and PHT (P = 0.012). KE peak power increased in EX by ∼27% (P = 0.001) but did not significantly change in PHT and SHAM groups. Expression of endothelial nitric oxide synthase increased significantly in both EX (P = 0.028) and PHT (P = 0.0095), but only EX resulted in increased angiogenesis. In conclusion, 6 weeks of localized PHT improved resistance artery function at rest and during exercise to the same extent as exercise training but did not yield significant improvements in performance. KEY POINTS: Many for whom exercise would be most beneficial are either unable to exercise or have a very low exercise tolerance. In these cases, an alternative treatment to combat declines in resistance artery function is needed. We tested the hypothesis that passive heat therapy (PHT) would increase resistance artery function, improve exercise haemodynamics and enhance exercise performance compared to a sham treatment, but less than aerobic exercise training. This report shows that 6 weeks of localized PHT improved resistance artery function at rest and during exercise to the same extent as exercise training but did not improve exercise performance. Additionally, muscle biopsy analyses revealed that endothelial nitric oxide synthase expression increased in both PHT and exercise training groups, but only exercise resulted in increased angiogenesis. Our data demonstrate the efficacy of applying passive heat as an alternative treatment to improve resistance artery function for those unable to receive the benefits of regular exercise.

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Background: This study investigates the effects of a 12-week circuit exercise program on blood pressure, vascular function, and inflammatory cytokines in older obese women with sarcopenia. Methods: Twenty-eight older obese women with sarcopenia (mean age: 78.2 ± 3.7 years) were randomly divided into an exercise group (EG, n = 14) and a control group (CG, n = 14). The EG participated in a 12-week circuit exercise training regimen, conducted three times weekly, with each session lasting between 45 to 75 minutes (progressively increased over time). The CG was advised to maintain their regular daily routines throughout the intervention period. All dependent variables, including blood pressure, vascular function, and inflammation cytokines, were evaluated pre- and post-intervention. Results: Positive changes were observed in the EG in body composition (body fat mass; p < 0.001, body fat percentage; p < 0.01, free-fat mass; p < 0.01), blood pressure (heart rate; p < 0.05, rate pressure product; p < 0.01), vascular function (brachial-ankle pulse wave velocity; p < 0.05, flow-mediated dilation; p < 0.001), and inflammation cytokines (interleukin-6; p < 0.05). In the CG, there was an increase in body fat mass (p < 0.05) and body fat percentage (p < 0.05), while no changes were observed in other variables. Conclusions: The 12-week circuit exercise program significantly reduced blood pressure, improved vascular function, and decreased inflammatory cytokines in obese older women with sarcopenia. However, individual variations in response highlight the need for personalized exercise regimens.