Changes In Vascular Function Research Articles

Effects of traditional Chinese exercise on vascular function in patients with Alzheimer's disease: A protocol for systematic review and network meta-analysis of randomized controlled trials.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with an insidious onset, usually characterized by memory impairment, visual-spatial skill impairment, executive dysfunction and personality behavioral changes. Studies have confirmed that vascular dysfunction may precede AD pathological changes and can present as vascular malformations, atherosclerosis, and impaired self-regulation, and can affect oxidative stress and amyloidosis. Therefore, it is important to improve or prevent vascular dysfunction in AD patients. Regular exercise can effectively inhibit the production of reactive oxygen species during the occurrence of AD and can improve the reduction of cerebral blood flow due to AD. Previous studies have shown that exercise can achieve superior clinical results in improving vascular function in AD patients. Therefore, we hypothesize that traditional Chinese exercises (TCEs) may have a good clinical effect in improving vascular function in patients with AD. We will search "PubMed," "the Cochrane Library," "Embase," "Web of Science," "CINAHL," "ProQuest Dissertations and Theses," and "ProQuest-Health & Medical Collection," "CNKI," "SinoMed," "VIP," and "Wanfang Data" to find randomized controlled trials of the effects of TCEs on AD vascular function from the creation of the database to the present, including at least 1 indicator in carotid intima-media thickness (cIMT), middle cerebral artery mean flow velocity (MFV), blood indicators [Heme Oxidase-1 (HO-1), angiopoietin I (Ang I), vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor, matrix metalloproteinase-9 (MMP-9)], and arterial stiffness [(Ankle Brachial Index (ABI), pulse wave velocity (PWV)]. For the included literature, Excel 2019 will be used for data extraction and collection. For the indicators that can be netted for network meta-analysis, Surface Under the Cumulative Ranking for each exercise modality will be calculated with the help of Stata 16.0 and rank, where the higher the SUCRA score, the higher the ranking. For the indicators that cannot be netted, Review Manager 5.4 will be used for meta-analysis will be performed to evaluate the improvement effect of TCEs on AD patients. This meta-analysis will further determine the efficacy and safety of TCEs on vascular function in AD patients. In this study, randomized controlled trials of the effects of TCEs on vascular function in AD patients will be selected to provide evidence-based medical evidence for promoting the application of TCEs by observing the order of advantages and disadvantages of various exercise modalities through network meta-analysis.

CGMP signaling: a potential therapeutic target for neurodegeneration in glaucoma?

cGMP signaling: a potential therapeutic target for neurodegeneration in glaucoma?

S-12-2: ENHANCING MAS1:ETBR INTERACTION AS A POTENTIAL VASOPROTECTIVE STRATEGY IN STROKE-PRONE SHR

We previously demonstrated that Ang-(1–7) has anti-inflammatory effects in endothelial cells by inducing interaction between Mas1 and ETBR. Using HTS of > 20,000 druggable compounds, we identified several compounds that enhance Mas1:ETBR interaction as a novel strategy to promote vasoprotection. The objective of this study was to evaluate effects of 2 candidate compounds, termed enhancers 3 and 4 (Enh3 and Enh4), on functional responses in vascular smooth muscle cells (VSMCs) and their therapeutic potential in hypertensive (SHRSP) rats. VSMCs from normotensive (WKY) and SHRSP rats were exposed to Enh3 and Enh4(10–5 M; 5–30 mins). Expression of pro-contractile and mitogenic molecules was assessed by immunoblotting. Ca2+ influx was evaluated using fluorescence microscopy. ROCK2 activity was assessed using a colorimetric immunoassay which detected MYPT1 phosphorylation at Thr696. Male SHRSP rats (18–21weeks) were treated subcutaneously with Enh4 (10 mg/kg/day) for 7 days. Changes in blood pressure and vascular function were assessed via radiotelemetry and wire myography respectively. In WKY VSMCs, Enh3 reduced basal ERK1/2 phosphorylation (26.8 ± 5.9% vs veh,), an effect absent in SHRSP VSMCs, while Enh4 had no effect. Only in SHRSP VSMCs, Enh3, but not Enh4, reduced basal AKT phosphorylation (63.5 ± 8.9% vs veh). Enh4, but not Enh3, reduced basal MLC20 phosphorylation (54.9 ± 7.5% vs veh) in WKY but not in SHRSP VSMCs. ET-1-induced Ca2+ influx in WKY and SHRSP VSMCs was unaffected by Enh3 and Enh4. Assessment of Ca2+ -independent contractile mechanisms in VSMCs showed that ROCK2 activity is increased in SHRSP compared to WKY VSMCs (WKY: 0.27 ± 0.05; SHRSP:4.78 ± 0.34) and Enh4, but not Enh3, reduced ROCK2 activity in SHRSP VSMCs (61.5 ± 0.43% vs veh). Enh4 treatment in SHRSP rats reduced daytime systolic (SBP), diastolic (DBP) and mean arterial pressure (MAP) (SBP:4.26 ± 1.98; DBP:1.48 ± 0.92; MAP:2.07 ± 0.99 vs veh) compared to baseline. Furthermore, Enh4 treatment reduced U46619 induced contraction in SHRSP rat vessels (Emax(Mn): Veh- 13.16 ± 1.81; Enh4- 9.48 ± 1.31). Taken together, enhancing Mas1:ETBR interaction attenuates mitogenic and contractile signaling pathways in WKY and SHRSP VSMCs, and does not increase Ca2+ signaling, important in VSMC contraction. Enhancing Mas1:ETBR interaction reduces blood pressure and improves vascular function in SHRSP rats. Hence, Mas1:ETBR enhancers may be of potential therapeutic use as a new vasoprotective strategy to improve vascular function and to reduce blood pressure in hypertension.

PS-BPC02-3: EVALUATION OF VASCULAR FUNCTION FOR PREDICTION OF RENAL PROGNOSIS IN JAPANESE PATIENTS WITH LIFESTYLE-RELATED DISEASES.

Background: Since chronic kidney disease (CKD) is associated with the development of serious cardiovascular diseases such as stroke, coronary artery disease and heart failure, prevention and early diagnosis of CKD are important clinical issues. Many risk factors including diabetes, hypertension, dyslipidemia, obesity, and cigarette smoking are known to be involved in the development of CKD; however, there is no available biomarker that can predict the progression of CKD at an early stage. Although it has been reported that glomerular endothelial injury causes development of CKD, it remains unclear whether evaluation of vascular endothelial function can predict renal prognosis. Therefore, in the present study, we examined the association between vascular endothelial function and longitudinal eGFR change in patients with lifestyle-related diseases. Methods: We retrospectively evaluated 341 Japanese patients (176 males and 165 females; mean age, 63.87 ± 12.02 years) with lifestyle-related diseases in whom baseline vascular function was evaluated by flow-mediated dilation (FMD) and brachial-ankle pulse wave velocity (baPWV) and in whom 24-month longitudinal eGFR values were recorded after vascular testing at Tokushima University Hospital and Anan Medical Center, Tokushima Japan. The association between values of FMD and eGFR slope and the association between values of baPWV and eGFR slope were statistically analyzed. Statistical significance was set at p < 0.05. Results: Single regression analysis showed that value of FMD was positively associated with eGFR slope in females (p < 0.001) and non-smoking males (p = 0.033) but not in smoking males (p = 0.133). Multiple regression analysis including confounding factors demonstrated that the value of FMD remained a contributor against annual eGFR decline in females (p = 0.002) and non-smoking males (p = 0.046) but not in smoking males (p = 0.266). On the other hand, the value of baPWV had no significant association with eGFR slope regardless of sex and smoking. Conclusions: In patients with lifestyle-related diseases, FMD value can be used for prediction of renal prognosis represented by the eGFR slope in females and non-smoking males. Thus, early comprehensive intervention for improving vascular endothelial function might lead to a better renal prognosis in female and non-smoking male patients with lifestyle-related diseases.

Mechanism of Hypoxia-Mediated Smooth Muscle Cell Proliferation Leading to Vascular Remodeling.

Vascular remodeling refers to changes in the size, contraction, distribution, and flow rate of blood vessels and even changes in vascular function. Vascular remodeling can cause cardiovascular and cerebrovascular diseases. It can also lead to other systemic diseases, such as pulmonary hypertension, pulmonary atherosclerosis, chronic obstructive pulmonary disease, stroke, and ascites of broilers. Hypoxia is one of the main causes of vascular remodeling. Prolonged hypoxia or intermittent hypoxia can lead to loss of lung ventilation, causing respiratory depression, irregular respiratory rhythms, and central respiratory failure. Animals that are unable to adapt to the highland environment are also prone to sustained constriction of the small pulmonary arteries, increased resistance to pulmonary circulation, and impaired blood circulation, leading to pulmonary hypertension and right heart failure if they live in a highland environment for long periods of time. However, limited studies have been found on the relationship between hypoxia and vascular remodeling. Therefore, this review will explore the relationship between hypoxia and vascular remodeling from the aspects of endoplasmic reticulum stress, mitochondrial dysfunction, abnormal calcium channel, disordered cellular metabolism, abnormal expression of miRNA, and other factors. This will help to understand the detailed mechanism of hypoxia-mediated smooth muscle cell proliferation and vascular remodeling for the better treatment and management of diseases due to vascular remodeling.

Effect of exercise on vascular function in hypertension patients: A meta-analysis of randomized controlled trials.

The purpose of this study was to systematically evaluate the effect of exercise on vascular function in patients with pre- and hypertension. A systematic review of articles retrieved via the PubMed, Embase, EBSCO, and Web of Science databases was conducted. All the randomized controlled trials published between the establishment of the databases and October 2022 were included. Studies that evaluated the effects of exercise intervention on vascular function in patients with pre- and hypertension were selected. A total of 717 subjects were included in 12 randomized controlled trials. The meta-analysis showed that in patients with pre- and hypertension, exercise can significantly reduce systolic blood pressure (SBP) (MD = -4.89; 95% CI, -7.05 to -2.73; P < 0.00001) and diastolic blood pressure (DBP) (MD = -3.74; 95% CI, -5.18 to -2.29; P < 0.00001) and can improve endothelium-dependent flow-mediated dilatation (MD = 2.14; 95% CI, 1.71-2.61; P < 0.00001), and exercise did not reduce pulse wave velocity (PWV) (MD = 0.03, 95% CI, -0.45-0.50; P = 0.92). Regression analysis showed that changes in exercise-related vascular function were independent of subject medication status, baseline SBP, age and duration of intervention. Aerobic, resistance, and high-intensity intermittent exercise all significantly improved SBP, DBP, and FMD in pre- and hypertensive patients, however, they were not effective in reducing PWV, and this effect was independent of the subject's medication status, baseline SBP, age and duration of intervention. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022302646.

필라테스 리포머 운동이 중년기 여성들의 심박변이도와 혈관기능에 미치는 영향

The purpose of this study was to investigate changes in heart rate variability and vascular function by applying Pilates Reformer exercise to middle-aged women. The Pilates Reformer exercise was conducted 3 times a week for 50 minutes a day for a total of 8 weeks. The heart rate variability showed a significant difference in the measurement timing of BC, PSI, TP, and MSI among the heart rate variability factors of the Pilates Reformer group after exercise, and there was no significant difference between the groups. In all factors, it was found that there was an interaction effect between measurement time*groups. Vascular function showed a significant decrease in the Pilates Reformer group after exercise than before exercise, but there was no significant difference between the measurement time and the group, but it was found that there was an interaction effect between the two groups. In summary, the Pilates Reformer exercise showed positive changes in heart rate variability and vascular function in middle-aged women. These results are thought to show the effect of exercise on middle-aged women who did not have much experience with the Pilates Reformer exercise. Through continuous exercise, the positive effect of Pilates Reformer was shown by reducing the heart rate, physical stress, and mental stress, and by increasing the total autonomic nerve that reflects the physical condition. Therefore, if the duration of the exercise is increased, and the intensity, frequency, and time are taken into consideration, a more effective program can be constructed and presented.

Aquaporin-8 overexpression is involved in vascular structure and function changes in placentas of gestational diabetes mellitus patients.

To study the role and mechanism of aquaporin-8 (AQP8) in placental vascular development in gestational diabetes mellitus (GDM), hematoxylin-eosin staining and immunohistochemistry were utilized to analyze the histopathological changes in placentas in GDM patients. Transwell, CCK-8, and tube formation assays were performed to examine cell migration, proliferation, and tube formation. AQP8, vascular cell adhesion molecule 1 (VCAM-1), tumor necrosis factor alpha (TNF)-α, and vascular endothelial growth factor (VEGF)-A expression levels were investigated. Relative to the control group, the placentas in the GDM group showed morphological changes, the number of microvessels in the placental villi arterioles was significantly higher, and the area of microvessels in the arterioles of placental villi was significantly lower. The expression levels of VCAM-1, TNF-α, VEGF-A, and AQP8 in the GDM placentas and human umbilical vein endothelial cells (HUVECs) stimulated by high glucose were significantly higher than those in the control group, and AQP8 was located in placental endothelial cells. Overexpression of glucose and AQP8 inhibited tube formation, migration, and proliferation in HUVECs. High glucose levels can induce dysfunction in vascular endothelial cells and lead to pathological changes in the placental vascular structure in GDM. AQP8 overexpression in placental GDM can inhibit endothelial cell behavior, cause endothelial cell dysfunction, and further participate in the occurrence and development of GDM placental vascular lesions.

Vascular smooth muscle cell dysfunction in neurodegeneration.

Vascular smooth muscle cells (VSMCs) are the key moderators of cerebrovascular dynamics in response to the brain's oxygen and nutrient demands. Crucially, VSMCs may provide a sensitive biomarker for neurodegenerative pathologies where vasculature is compromised. An increasing body of research suggests that VSMCs have remarkable plasticity and their pathophysiology may play a key role in the complex process of neurodegeneration. Furthermore, extrinsic risk factors, including environmental conditions and traumatic events can impact vascular function through changes in VSMC morphology. VSMC dysfunction can be characterised at the molecular level both preclinically, and clinically ex vivo. However the identification of VSMC dysfunction in living individuals is important to understand changes in vascular function at the onset and progression of neurological disorders such as dementia, Alzheimer's disease, and Parkinson's disease. A promising technique to identify changes in the state of cerebral smooth muscle is cerebrovascular reactivity (CVR) which reflects the intrinsic dynamic response of blood vessels in the brain to vasoactive stimuli in order to modulate regional cerebral blood flow (CBF). In this work, we review the role of VSMCs in the most common neurodegenerative disorders and identify physiological systems that may contribute to VSMC dysfunction. The evidence collected here identifies VSMC dysfunction as a strong candidate for novel therapeutics to combat the development and progression of neurodegeneration, and highlights the need for more research on the role of VSMCs and cerebrovascular dynamics in healthy and diseased states.

Effects of tofacitinib therapy on arginine and methionine metabolites in association with vascular pathophysiology in rheumatoid arthritis: A metabolomic approach.

Rheumatoid arthritis (RA) has been associated with changes in lipid, arginine and NO metabolism with increased cardiovascular (CV) risk. The aim of this study is to evaluate the effect of tofacitinib, a Janus kinase (JAK) inhibitor, on arginine and methionine metabolism in correlation with inflammation, functional and pathological vascular changes during one-year treatment of patients with RA. Thirty RA patients with active disease were treated with either 5 mg bid or 10 mg bid tofacitinib for 12 months. We determined DAS28, CRP, IgM rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) levels. We assessed brachial artery flow-mediated vasodilation (FMD), carotid intima-media thickness (IMT) and pulse-wave velocity (PWV) by ultrasound at baseline and after 6 and 12 months. We also determined plasma L-arginine, L-citrulline, L-ornithine, inducible nitric oxide synthase (iNOS), asymmetric (ADMA) and symmetric dimethylarginine (SDMA), L-N-monomethyl-arginine (L-NMMA), cysteine, homocysteine, and methionine levels at these time points. Twenty-six patients (13 on each arm) completed the study. CRP, ESR and DAS28 decreased significantly during one-year treatment with tofacitinib. Arginine and ADMA showed a negative univariate correlation with CRP but not with FMD, PWV or IMT. Tofacitinib at 10 mg bid significantly increased L-arginine, L-ornithine, iNOS and methionine levels after 12 months. ADMA and SDMA levels did not change in our study. Methionine showed negative correlation with FMD at baseline and positive correlation with PWV after 12 months. No change was observed in FMD and PWV but a significant increase was measured in IMT at 6 and 12 months. Multivariate analysis indicated variable correlations of L-arginine, L-citrulline, ADMA, L-NMMA, homocysteine and methionine with DAS28, CRP, ESR and RF but not with anti-CCP after one-year treatment. With respect to vascular pathophysiology, only PWV and methionine correlated with each other. One-year tofacitinib treatment suppressed systemic inflammation and improved functional status in RA. FMD, PWV have not been affected by one-year tofacitinib treatment., while IMT increased further despite treatment. Increased arginine and methionine might contribute to the anti-inflammatory effects of tofacitinib. Increased arginine availability with no changing ADMA may protect FMD and PWV from deterioration. The increase of IMT in the anti-inflammatory environment cannot be explained by arginine or methionine metabolism in this study.

Abstract 12217: Effect of Repeated Binge Drinking in Mid-Life Adults on Vascular Function

Introduction: Age-related changes in vascular function, including endothelial dysfunction and arterial stiffening, contribute to the development of cardiovascular disease. “Mid-life adults”, defined as age 50-64, begin to show signs of vascular aging. One in five mid-life adults engage in binge drinking and our previous studies in young adults showed that repeated binge drinking was associated with endothelial dysfunction and arterial stiffening. However, it is unclear how binge drinking influences vascular function in aged individuals. Therefore, the purpose of this study is to investigate endothelial function and arterial stiffness in mid-life adults who binge drink regularly (binge drinkers) compared to those who did not drink alcohol (alcohol abstainers). Methods: Twelve apparently healthy mid-life men and postmenopausal women, with no smoking history were included in this study (mean±SEM, age: 57±1 years, body mass index: 26.0±0.8 kg/cm 2 , systolic blood pressure: 119±5 mmHg). Alcohol use was assessed by the Alcohol Use Disorders Identification Test (AUDIT) and dried blood spot phosphatidylethanol. Endothelial function was assessed by brachial artery response to reactive hyperemia (flow-mediated dilation, FMD) via ultrasonography. Arterial stiffness was assessed by carotid to femoral pulse wave velocity (cfPWV) via use of the cuff-based SphygmoCor Xcel. Results: Binge drinkers (n=6) had an AUDIT score≥5 (11.8±2.1) and positive phosphatidylethanol level (162±103 ng/mL), while alcohol abstainers (n=6) had an AUDIT score≤1 (0.8±0.2) and negative phosphatidylethanol level. Compared to alcohol abstainers, binge drinkers had a lower brachial artery FMD (alcohol abstainers vs. binge drinkers: 9.8±1.2% vs. 5.1±0.9%, P=0.01), but similar cfPWV (7.2±0.7 vs. 7.0±0.5 m/sec, P=0.8). Conclusions: Our results indicate that compared to mid-life adult alcohol abstainers, binge drinkers had lower endothelial function, but similar arterial stiffness. These findings suggest that repeated binge drinking may further impair endothelial function throughout the aging process.

Abstract 15569: Association of Volatile Organic Compound Levels With Pod-Based Electronic Cigarette-Induced Changes in Vascular Function of Young Adults

Introduction: Pod-based electronic (e-) cigarettes including JUUL are the most frequently used product type in young adults. Here, we evaluated the acute and chronic impact of pod-based e-cigarettes on vascular health and their relation to volatile organic compound (VOC) exposure. Methods: We performed a short-term observational study of healthy young adults (N = 106) and recruited pod-based e-cigarette users (N = 48), combustible cigarette users (N = 21), and tobacco nonusers (N = 37). Vascular function via flow-mediated dilation and blood pressure (BP) was measured before and after 10-min structured product use of the participant's own product. Urinary VOCs were measured 1 hour after product use. In human aortic endothelial cells (HAECs) in culture exposed to select VOCs, nitric oxide production was measured with DAF-2 indicator. Results: Among pod-based e-cigarette users, 64% were exclusive users including 37% who had never used combustible cigarettes. Pod-based e-cigarette users and combustible cigarette users had higher systolic BP compared to non-users (121±11 mmHg, 121±13 mmHg, 112±10 mmHg, P=0.0004). Structured pod-based e-cigarette use acutely decreased flow-mediated dilation (-3.2±2.7%), raised systolic and diastolic BP (6±8mmHg, 4±5mmHg) and heart rate (5±7bpm), similar to combustible cigarette use (-2.6±2.6%, 9±8mmHg, 6±5mmHg, 6±6bpm P=0.83, 0.3, 0.4, 0.56 vs pod-based), and to a greater extent than nonuse (0.3±4.1%, 0.7±5mmHg, 0.3±3mmHg, -3±4bpm, P=1.0x10-7, 0.002, 0.003, 2.6x10 -7 ). Differences remained in models adjusted for age, sex, and race. The effect of pod-based e-cigarette use was similar in adults who had never used combustible cigarettes. Levels of VOCs acrolein, acrylamide, acrylonitrile, and crotonaldehyde were associated with changes in vascular health measures. Exposure of HAECs in culture to acrolein and acrylamide reduced acetylcholine-stimulated nitric oxide production. Conclusions: Our findings demonstrated that pod-based e-cigarette use had acute and chronic vascular effects in healthy young adults including those who never used combustible cigarettes. Select VOC metabolites were associated with the vascular changes and altered nitric oxide production suggesting relevance to vascular health.

Abstract 13592: Gender Related Divergences in Cardiac and Vascular Function With Age

Introduction: Heart failure with preserved ejection fraction (HFpEF) is a disease of advanced aging that disproportionately affects women. Diastolic function changes with age and it is unknown if gender-related differences in progression exist. Understanding ages at which parameters of vascular and diastolic function diverge may provide insight into the differential risk of HFpEF between genders. Methods: Sedentary but healthy non-obese subjects aged 20-90 (n=178, 58% female; avg age 56 ± 13 yrs) underwent measures of pulmonary capillary wedge pressure (PCWP; right heart catheterization), blood pressure and cardiac output (acetylene rebreathe). Diastolic function was assessed by Doppler echocardiogram. A generalized linear model was used to estimate effects of age for each measured hemodynamic parameter as a function of gender. Results: Across age, women had higher systolic blood pressure (SBP) (age*gender p=0.025, age p&lt;0.001) and total peripheral resistance (TPR) (age*gender p=0.053, age p&lt;0.001). Changes in TPR were apparent at age 26 while SBP diverged at age 55. (Figure) Women had slower early diastolic recoil (e’) (age*gender p&lt;0.001) starting at age 55. While E wave velocity was lower in women, age-related decline was similar to men. E/e’ was higher in women (age*gender p=0.007) and diverged at a young age (28). PCWP declined with age similarly in both men and women. Systolic velocity (s’) declined in early middle age (42) in women (age*gender p=0.007, age p=0.002). Conclusions: Women experience greater changes in cardiac and vascular function with age than men. The age at which these parameters diverge differs, with evidence for decline in vascular function and cardiac contractility occurring at young ages in women while changes in SBP and diastolic recoil occur after age 55. Understanding lifestyle and hormonal factors that influence these differences may help elucidate HFpEF risk factors that are modifiable and serve as a target for therapy.

Acute effects of electronic cigarettes on vascular endothelial function: a systematic review and meta-analysis of randomized controlled trials.

The effects of e-cigarettes on endothelial function remained controversial. The study aimed to investigate the effects of e-cigarettes on vascular endothelial function. PubMed, Web of Science, Embase, and Cochrane Library were searched up to December 2021. We only included the studies in which the control group included vaping without nicotine and tobacco. Pairwise and network meta-analyses were conducted for flow-mediated dilation (FMD), pulse wave velocity (PWV), and heart rate corrected augmentation index (AIx75). Eight studies involving 372 participants were eligible for this review. Compared with vaping without nicotine, e-cigarettes significantly increase in PWV (mean difference = 3.09; 95% confidential interval: 1.51-4.68, P < 0.001) and AIx75 (mean difference = 2.11; 95% confidential interval: 1.02-3.21, P < 0.001) indicators, but not affect FMD (mean difference = 0.78; 95% confidential interval: -0.08 to 1.64, P = 0.075). But compared with traditional tobacco, e-cigarettes did not affect FMD (mean difference = 0.28, 95% confidential interval: -0.45 to 0.59, P = 0.084). According to surface under the cumulative ranking curve (SUCRA), the e-cigarette ranked first for FMD (SUCRA = 97%), tobacco ranked first for PWV (SUCRA = 75%), and AIx75 (SUCRA = 99%). In summary, evidence from our pooled analyses indicated that acute inhalation of e-cigarettes leads to negative changes in vascular endothelial function. E-cigarettes cannot be used as an alternative to public health strategies for tobacco control and should not be considered cardiovascular safety products. More future research should be conducted to verify our findings.

Molecular Mechanisms of Ischaemia-Reperfusion Injury and Regeneration in the Liver-Shock and Surgery-Associated Changes.

Hepatic ischemia-reperfusion injury (IRI) represents a major challenge during liver surgery, liver preservation for transplantation, and can cause hemorrhagic shock with severe hypoxemia and trauma. The reduction of blood supply with a concomitant deficit in oxygen delivery initiates various molecular mechanisms involving the innate and adaptive immune response, alterations in gene transcription, induction of cell death programs, and changes in metabolic state and vascular function. Hepatic IRI is a major cause of morbidity and mortality, and is associated with an increased risk for tumor growth and recurrence after oncologic surgery for primary and secondary hepatobiliary malignancies. Therapeutic strategies to prevent or treat hepatic IRI have been investigated in animal models but, for the most part, have failed to provide a protective effect in a clinical setting. This review focuses on the molecular mechanisms underlying hepatic IRI and regeneration, as well as its clinical implications. A better understanding of this complex and highly dynamic process may allow for the development of innovative therapeutic approaches and optimize patient outcomes.

Prenatal exposure to a low dose of BPS causes sex-dependent alterations to vascular endothelial function in adult offspring.

Background: Bisphenol S (BPS) is among the most commonly used substitutes for Bisphenol A (BPA), an endocrine disrupting chemical used as a plasticizer in the manufacture of polycarbonate plastics and epoxy resins. Bisphenols interfere with estrogen receptor (ER) signaling, which modulates vascular function through stimulation of nitric oxide (NO) production via endothelial nitric oxide synthase (eNOS). BPS can cross into the placenta and accumulates in the fetal compartment to a greater extent than BPA, potentially interfering with key developmental events. Little is known regarding the developmental impact of exposure to BPA substitutes, particularly with respect to the vasculature. Objective: To determine if prenatal BPS exposure influences vascular health in adulthood. Methods: At the time of mating, female C57BL/6 dams were administered BPS (250 nM) or vehicle control in the drinking water, and exposure continued during lactation. At 12-week of age, mesenteric arteries were excised from male and female offspring and assessed for responses to an endothelium-dependent (acetylcholine, ACh) and endothelium-independent (sodium nitroprusside, SNP) vasodilator. Endothelium-dependent dilation was measured in the presence or absence of L-NAME, an eNOS inhibitor. To further explore the role of NO and ER signaling, wire myography was used to assess ACh responses in aortic rings after acute exposure to BPS in the presence or absence of L-NAME or an ER antagonist. Results: Increased ACh dilation and increased sensitivity to Phe were observed in microvessels from BPS-exposed females, while no changes were observed in male offspring. Differences in ACh-induced dilation between control or BPS-exposed females were eliminated with L-NAME. Increased dilatory responses to ACh after acute BPS exposure were observed in aortic rings from female mice only, and differences were eliminated with inhibition of eNOS or inhibition of ER. Conclusion: Prenatal BPS exposure leads to persistent changes in endothelium-dependent vascular function in a sex-specific manner that appears to be modulated by interaction of BPS with ER signaling.

Swimming Exercise Alleviates Endothelial Mitochondrial Fragmentation via Inhibiting Dynamin-Related Protein-1 to Improve Vascular Function in Hypertension.

Regular exercise has been recommended clinically for all individuals to protect against hypertension but the underlying mechanisms are not fully elucidated. We recently found a significant mitochondrial fragmentation in the vascular endothelium of hypertensive human subjects. In this study, we investigated whether exercise could restore endothelial mitochondrial dynamics and thus improve vascular function in hypertension. Vascular endothelial mitochondrial morphological alterations were examined in patients with hypertension and hypertensive animal models. Furthermore, swimming exercise-induced endothelial mitochondrial dynamics and vascular function changes were investigated in spontaneously hypertensive rats (SHRs). Mitochondrial fragmentation with an elevated mitochondrial fission mediator Drp1 (dynamin-related protein-1) was observed in the mesenteric artery endothelium from hypertensive patients. A similar mitochondrial fragmentation with increased Drp1 expression were exhibited in the aortic endothelium of angiotensin II-induced hypertensive mice and SHRs. Interestingly, swimming exercise significantly reduced vascular Drp1 expression and alleviated endothelial mitochondrial fragmentation, thus improving blood pressure in SHRs. In cultured endothelial cells, angiotensin II exposure induced Drp1 upregulation, mitochondrial fragmentation and dysfunction, and reduced nitric oxide production, which was blunted by Drp1 genetic reduction or its inhibitor Mdivi-1. Mdivi-1 administration also ameliorated endothelial mitochondrial fragmentation, vascular dysfunction and blood pressure elevation in SHRs while swimming exercise plus Mdivi-1 treatment provided no additional benefits, suggesting that Drp1 inhibition may partially contribute to swimming exercise-conferred anti-hypertensive effects. These findings suggest that swimming exercise alleviates endothelial mitochondrial fragmentation via inhibiting Drp1, which may contribute to exercise-induced improvement of vascular function and blood pressure in hypertension.

Piezo1 in vascular remodeling of atherosclerosis and pulmonary arterial hypertension: A potential therapeutic target.

Vascular remodeling (VR) is a structural and functional change of blood vessels to adapt to the changes of internal and external environment. It is one of the common pathological features of many vascular proliferative diseases. The process of VR is mainly manifested in the changes of vascular wall structure and function, including intimal hyperplasia, thickening or thinning of media, fibrosis of adventitia, etc. These changes are also the pathological basis of aging and various cardiovascular diseases. Mechanical force is the basis of cardiovascular biomechanics, and the newly discovered mechanical sensitive ion channel Piezo1 is widely distributed in the whole cardiovascular system. Studies have confirmed that Piezo1, a mechanically sensitive ion channel, plays an important role in cardiovascular remodeling diseases. This article reviews the molecular mechanism of Piezo1 in atherosclerosis, hypertension and pulmonary hypertension, in order to provide a theoretical basis for the further study of vascular remodeling.

Exercise with blood flow restriction improves muscle strength and mass while preserving the vascular and microvascular function and structure of older adults.

Changes in muscle mass, strength, vascular function, oxidative stress, and inflammatory biomarkers were compared in older adults after resistance training (RT) performed with low-intensity without blood flow restriction (RT-CON); low-intensity with BFR (RT-BFR); and high-intensity without BFR (RT-HI). Thirty-two untrained individuals (72±7 y) performed a 12-week RT after being randomized into three groups: RT-CON -30% of 1 repetition maximum (RM); RT-BFR -30% of 1RM and mild BFR (50% of arterial occlusion pressure); RT-HI -70% of 1 RM. Improvements in handgrip strength were similar in RT-BFR (17%) and RT-HI (16%) vs. RT-CON (-0.1%), but increases in muscle mass (6% vs. 2% and -1%) and IGF-1 (2% vs. -0.1% and -1.5%) were greater (p < 0.05) in RT-BFR vs. RT-HI and RT-CON. Changes in vascular function, morphology, inflammation, and oxidative stress were similar between groups, except for time to reach maximum red blood cell velocity which showed a greater reduction (p < 0.05) in RT-BFR (-55%) vs. RT-HI (-11%) and RT-CON (-4%). RT with low intensity and mild BFR improved muscle strength and mass in older individuals while preserving vascular function. This modality should be considered an adjuvant strategy to improve muscle function in older individuals with poor tolerance to high loads.

Acute effect of high-intensity interval exercise on vascular endothelial function and possible mechanisms of wall shear stress in young obese males.

Objective: To investigate the mechanisms of wall shear stress (WSS) responsible for the effects of high-intensity interval exercise (HIIE) on vascular endothelial function in young obese males. Methods: A within-subject study design was used. We examined the response of the reactive hyperemia index (RHI) to acute HIIE in young obese males (n = 20, age = 20.38 ± 1.40 years, body mass index [BMI] = 31.22 ± 3.57, body fat percentage [BF (%)] = 31.76 ± 3.57). WSS was manipulated using 100, 80, or 60 mmHg cuff inflation during the HIIE to determine the proper inflation capable of maintaining WSS near baseline levels. One-way repeated measures analysis of variance and LSD post hoc tests were performed to compare changes in WSS and vascular endothelial function at baseline HIIE and following HIIE using different cuff inflations. Results: There were no significant differences in RHI and WSS between the three cuff inflation values (p > 0.05). WSS was significantly higher in obese male individuals after HIIE and HIIE with 100 mmHg cuff inflation (p = 0.018, p = 0.005) than that at baseline, with no significant differences observed comparing HIIE and HIIE with 100 mmHg inflation (p = 0.23). The RHI after HIIE was significantly higher (p = 0.012) than that at baseline, while no significant differences were detected after HIIE at 100 mmHg (p = 0.91). The RHI was significantly lower after HIIE with 100 mmHg than that after HIIE (p = 0.007). WSS (p = 0.004) and RHI (p = 0.017) were significantly higher after HIIE than that at baseline, while no significant differences were observed after HIIE with either 80 or 60 mmHg cuff inflation (baseline vs. HIIE + 80 mmHg: WSS: p = 0.33, RHI: p = 0.38; baseline vs. HIIE + 60 mmHg: WSS: p = 0.58, RHI: p = 0.45). WSS was similar to HIIE, after HIIE with either 80 or 60 mmHg inflation (p = 0.36, p = 0.40). However, RHI was significantly higher for HIIE than for HIIE with both 80 and 60 mmHg inflation (p = 0.011, p = 0.006). Conclusion: HIIE could significantly improve WSS and vascular endothelial function. HIIE intervention with 60 or 80 mmHg inflation might enhance WSS near the baseline level. HIIE-induced acute changes in WSS may provide the primary physiological stimulus for vascular endothelial adaptation to HIIE in young obese males.