Arterial Endothelial Dysfunction Research Articles

Recovery of Ischemic Limb and Femoral Artery Endothelial Function Are Preserved in Mice with Dextran Sodium Sulfate-Induced Chronic Colitis

Simple SummaryThe present study examines the effect of experimental inflammatory bowel disease on femoral artery endothelial function and limb ischemia recovery in female mice using a chronic colitis model induced by dextran sodium sulfate exposure. As expected, plasma levels of proinflammatory cytokines, including interleukin-6, interleukin-17, tumor necrosis factor alpha, and chemokine ligand 1, were significantly increased in the chronic colitis model. However, ROS levels in the ischemic muscle tissues were not significantly increased in mice with colitis as compared to controls. There were no significant changes in endothelium-dependent or -independent vasodilation of femoral artery between the colitis model and the control. Recovery of function and blood flow of the ischemic limb and capillary density in the ischemic muscle were preserved in the colitis model as compared with the control.Inflammatory bowel disease (IBD) produces significant systemic inflammation and increases the risk of endothelial dysfunction and peripheral artery disease. Our recent study demonstrated that abdominal aortic endothelial cell function was impaired selectively in female mice with chronic colitis. This study aimed to test the hypothesis that experimental colitis leads to femoral artery endothelial cell dysfunction and impairs limb ischemia recovery in female mice. An experimental chronic colitis model was created in female C57BL/6 mice with dextran sodium sulfate (DSS) treatment. Unilateral hind limb ischemia was produced by femoral artery ligation. Limb blood perfusion, vascular density, tissue ROS levels, and plasma levels of proinflammatory cytokines were assessed. Femoral artery endothelium-dependent and -independent vasodilation of the contralateral limb were evaluated ex vivo using acetylcholine and nitroglycerin, respectively. As expected, the plasma levels of proinflammatory cytokines, including tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, and IL-17, were significantly increased in the DSS-induced colitis model. However, ROS levels in the ischemic muscle tissues were not significantly increased in colitis model as compared to the controls. There were no significant changes in endothelium-dependent or -independent vasodilation of the femoral artery between colitis model and the control. Recovery of function and blood flow in the ischemic limb and capillary density in the ischemic gastrocnemius muscle were preserved in the colitis model as compared with the control. The data demonstrated that DSS-induced chronic colitis had no significant impact on femoral artery endothelial function or ischemic limb recovery in female mice.

Vascular endothelial function as an early sign of vascular ageing in patients with metabolic syndrome

Background and Aims : Objective is to evaluate signs of early vascular ageing, namely arterial stiffness, intima-media thickness and endothelial dysfunction, among people with metabolic syndrome by comparing the results of pulse wave velocity (PWV), intima-media thickness (IMT) and flow-mediated dilation FMD) techniques, respectively. Also, we aim to examine the correlation between these methods as well as relationship with cardiovascular risk factors.

Role of arterial stiffness and endothelial dysfunction on lower limb performance in older adults with type 2 diabetes: A cross-sectional study

AimTo verify whether arterial stiffness and endothelial dysfunction influence lower limb muscle strength and gait speed in older adults with type 2 diabetes mellitus (T2DM). MethodsCross-sectional study including seventy-eight older adults with T2DM (aged 67 ± 6 years and 42 % male). Arterial stiffness was assessed using pulse wave velocity (PWV), while endothelial function was measured by flow-mediated dilation (FMD). Lower limb muscle strength and gait speed were assessed using the 30-second chair stand test (30s-CST) and 10-Meter Walk Test, respectively. ResultsBoth PWV (m/s) and FMD (%) were univariately associated with number of repetitions in 30s-CST and gait speed (P < 0.05). After control for age, sex and body mass index, PWV remained associated with repetitions in 30s-CST (95 % CI: −0.494 to −0.054; P = 0.015) and gait speed (95 % CI: −0.039 to −0.002; P = 0.031). After adjustments for control variables, T2DM duration and glycemic control, FMD was associated with repetitions in 30s-CST (95 % CI: 0.008 to 0.324; P = 0.039) and gait speed (95 % CI: 0.011 to 0.038; P = 0.001). ConclusionIn older adults with T2DM, both arterial stiffness and endothelial dysfunction are associated with decreased leg muscle strength and slower gait speed.

Sex differences in vascular aging and impact of GPER deletion.

Aging is a nonmodifiable risk factor for cardiovascular disease associated with arterial stiffening and endothelial dysfunction. We hypothesized that sex differences exist in vascular aging processes and would be attenuated by global deletion of the G protein-coupled estrogen receptor. Blood pressure was measured by tail-cuff plethysmography, pulse wave velocity (PWV) and echocardiography were assessed with high-resolution ultrasound, and small vessel reactivity was measured using wire myography in adult (25 wk) and middle-aged (57 wk) male and female mice. Adult female mice displayed lower blood pressure and PWV, but this sex difference was absent in middle-aged mice. Aging significantly increased PWV but not blood pressure in both sexes. Adult female carotids were more distensible than males, but this sex difference was lost during aging. Acetylcholine-induced relaxation was greater in female than male mice at both ages, and only males showed aging-induced changes in cardiac hypertrophy and function. GPER deletion removed the sex difference in PWV and ex vivo stiffness in adult mice. The sex difference in blood pressure was absent in KO mice and was associated with endothelial dysfunction in females. These findings indicate that the impact of aging on arterial stiffening and endothelial function is not the same in male and female mice. Moreover, nongenomic estrogen signaling through GPER impacted vascular phenotype differently in male and female mice. Delineating sex differences in vascular changes during healthy aging is an important first step in improving early detection and sex-specific treatments in our aging population.NEW & NOTEWORTHY Indices of vascular aging were different in male and female mice. Sex differences in pulse wave velocity, blood pressure, and large artery stiffness were abrogated in middle-aged mice, but the female advantage in resistance artery vasodilator function was maintained. GPER deletion abrogated these sex differences and significantly reduced endothelial function in adult female mice. Additional studies are needed to characterize sex differences in vascular aging to personalize early detection and treatment for vascular diseases.

Temporal changes in coronary artery function and flow velocity reserve in mice exposed to chronic intermittent hypoxia.

Obstructive sleep apnea (OSA) is a chronic condition characterized by intermittent hypoxia (IH) that is implicated in an increased risk of cardiovascular disease (i.e., coronary heart disease, CHD) and associated with increased overall and cardiac-specific mortality. Accordingly, we tested the hypothesis that experimental IH progressively impairs coronary vascular function and in vivo coronary flow reserve. Male C57BL/6J mice (8-week-old) were exposed to IH (FiO2 21% 90 s-6% 90 s) or room air (RA; 21%) 12 h/day during the light cycle for 2, 6, 16, and 28 weeks. Coronary artery flow velocity reserve (CFVR) was measured at each time point using a Doppler system. After euthanasia, coronary arteries were micro-dissected and mounted on wire myograph to assess reactivity to acetylcholine (ACh) and sodium nitroprusside (SNP). Endothelium-dependent coronary relaxation to ACh was preserved after 2 weeks of IH (80.6 ± 7.8%) compared to RA (87.8 ± 7.8%, p = 0.23), but was significantly impaired after 6 weeks of IH (58.7 ± 16.2%, p = 0.02). Compared to ACh responses at 6 weeks, endothelial dysfunction was more pronounced in mice exposed to 16 weeks (48.2 ± 5.3%) but did not worsen following 28 weeks of IH (44.8 ± 11.6%). A 2-week normoxic recovery after a 6-week IH exposure reversed the ACh abnormalities. CFVR was significantly reduced after 6 (p = 0.0006) and 28 weeks (p < 0.0001) of IH when compared to controls. Chronic IH emulating the hypoxia-re-oxygenation cycles of moderate-to-severe OSA promotes coronary artery endothelial dysfunction and CFVR reductions in mice, which progressively worsen until reaching asymptote between 16 and 28 weeks. Normoxic recovery after 6 weeks exposure reverses the vascular abnormalities.

Prenatal Hypoxia is Associated with Coronary Artery Endothelial Dysfunction in Male and Female Offspring

IntroductionFetal hypoxia is a common consequence of complicated pregnancies and is linked to the development of cardiovascular (CV) dysfunction in the offspring. We showed an impaired cardiac function in adult prenatal hypoxia offspring, however, the mechanisms are not known. Coronary artery endothelial dysfunction has been shown to contribute to the development of cardiac dysfunction, however, whether endothelial function is impaired in coronary arteries of prenatal hypoxia offspring is unknown. We hypothesize that prenatal hypoxia leads to impaired coronary artery endothelial function in adult male and female offspring.MethodsPregnant Sprague‐Dawley rats were exposed to normoxia (21% O2) or hypoxia (11% O2; p‐Hyp) on gestational days 15‐21 (term=22 days). Male and female offspring were aged to 9‐9.5 months. Left anterior descending coronary arteries were isolated (n=5‐7/group), and endothelium‐dependent vasodilation to methylcholine (MCh) and endothelium‐independent vasodilation to the nitric oxide (NO) donor sodium nitroprusside (SNP) were assessed by wire myography. To assess the contribution of endothelial vasodilation pathways, MCh‐curves were performed in the presence/absence of inhibitors of nitric oxide synthase (L‐NAME), prostaglandin H synthase ([PGHS]; meclofenamate), or small‐ and intermediate‐conductance Ca2+‐activated potassium channels (apamin and TRAM‐34, respectively). Data were summarized as Emax (maximum vasodilation response), pEC50 (concentration required to produce 50% of Emax) or Area Under the Curve (AUC). Data were compared by two‐way ANOVA (Sidak's post hoc test); p&lt;0.05 was significant.ResultsMch‐induced vasodilation (Emax) was decreased in p‐Hyp males (p=0.006) and females (p=0.032) compared to normoxia offspring. L‐NAME completely inhibited vasodilation (AUC) in normoxia and p‐Hyp males (p&lt;0.0001). In the female offspring, incubation with L‐NAME completely inhibited vasodilation in the normoxia group (p&lt;0.0001), but to a lesser extent (Emax ~15%) in the p‐Hyp offspring (p&lt;0.0001). In contrast, meclofenamate did not alter MCh‐induced vasodilation (AUC) in males, while in females, meclofenamate increased vasodilation to MCh in the p‐Hyp group only (p=0.04). Apamin and TRAM‐34 did not alter responses to MCh in any of the groups. SNP sensitivity (pEC50) was decreased in p‐Hyp females compared to normoxia controls (p=0.012), without changes in males.ConclusionsOur data suggest that prenatal hypoxia leads to coronary artery endothelial dysfunction in male and female offspring. In prenatal hypoxia males, NO contribution to endothelium‐mediated vasodilation was reduced. In females, prenatal hypoxia increased PGHS‐dependent vasoconstriction and decreased smooth muscle sensitivity to NO. Understanding the mechanistic pathways involved in programming of CV disease may allow for the development of future prenatal and postnatal therapeutic interventions.

Effect of Selected After-School Physical Activity Protocol on Levels of CRP, miR-125a-5p, and Lipid Profile of Children with Overweight/Obesity

Background: One of the causes of arterial endothelial dysfunction in adulthood is obesity or overweight in childhood or adolescence. Objectives: This study aimed to investigate the effect of a selected after-school physical activity protocol on peak oxygen consumption (VO2peak), C-reactive protein (CRP), miR-125a-5p level, and lipid profile of male children with overweight/obesity. Methods: Twenty-four boy children with overweight/obesity (aged 13 - 15 years) were assigned to after-school physical activity (APA, BMI = 27.5±1.4 kg/m2, n = 12) and control (CON, BMI = 26.28 ± 2.3 kg/m2, n = 12) groups. The APA participants took part in exercise intervention for 12 weeks, three sessions per week. Changes in VO2peak, CRP, miR-125a-5p, and lipid profile of participants were assessed before and after exercise interventions. Results: There were significant reductions in CRP (-27.7% vs. 9.7%), miR-125a-5p (36.7% vs. 7.6%), fat percentage (-8.24% vs. 0.7%), LDL (-17.66% vs. 1.9%), and triglycerides (-15.7% vs. 5.9%) in APA and CON groups after 12-week exercise intervention (P &lt; 0.05). In contrast, a significant increase was found in HDL (7.7% vs. -0.6%) and VO2peak (4.83% vs. -1.6%) (P &lt; 0.05). There were significant between-group differences in all measured variables, except for BMI. Conclusions: After-school physical activity effectively improved the endothelial dysfunction and lipid profile of adolescents with overweight/obesity. Therefore, based on the positive effects of these physical activities performed out of school, further use of after-school physical activity programs is suggested.

Elevated Aortic Stiffness After Pediatric Heart Transplantation

<h3>Purpose</h3> Elevated arterial stiffness causes abnormal transmission of pulse pressure leading to target organ damage and increased risk for cardiovascular diseases. Increased arterial stiffness and endothelial dysfunction have been hypothesized as one of the mechanisms for the development of microvascular dysfunction and coronary allograft vasculopathy (CAV) after heart transplantation (HT). We sought to assess aortic stiffness and distensibility in pediatric post-HT patients and healthy controls. <h3>Methods</h3> We performed a prospective study analyzing the ascending (donor tissue) and descending aorta (recipient tissue) using transthoracic echocardiographic M-mode measurements in healthy controls and HT patients aged <21 years. Patients with existing vascular, rheumatologic, connective tissue diseases and hypertension were excluded. The descending aorta M-mode was obtained from the subcostal long axis view and the ascending aorta M-mode was obtained from the parasternal long axis view 3-5mm above the sinotubular junction. Two independent reviewers performed the measurements over 2-3 cardiac cycles, which were averaged. We calculated Aortic Distensibility (AD) and Aortic Stiffness Index (ASI) utilizing previously validated methods as shown in Table 1. <h3>Results</h3> We recruited 27 HT patients, of which 10 had congenital heart disease and 17 had cardiomyopathy and 28 healthy controls. Study results are summarized in Table 1. There was no significant difference in demographics between groups. Diastolic blood pressure was significantly higher in the transplant group. HT patients demonstrated significantly higher ascending aortic end diastolic dimensions, ascending aortic stiffness index and lower ascending aortic distensibility compared to healthy controls. Time from transplant did not affect these parameters. In 3 patients with CAV, the stiffness parameters were comparable to post-HT patients without CAV. <h3>Conclusion</h3> Our study demonstrated higher ascending aortic stiffness and lower distensibility in post-HT patients.

Circulatory metabolites trigger ex vivo arterial endothelial cell dysfunction in population chronically exposed to diesel exhaust

BackgroundChronic exposure to diesel exhaust has a causal link to cardiovascular diseases in various environmental and occupational settings. Arterial endothelial cell function plays an important role in ensuring proper maintenance of cardiovascular homeostasis and the endothelial cell dysfunction by circulatory inflammation is a hallmark in cardiovascular diseases. Acute exposure to diesel exhaust in controlled exposure studies leads to artery endothelial cells dysfunction in previous study, however the effect of chronic exposure remains unknown.ResultsWe applied an ex vivo endothelial biosensor assay for serum samples from 133 diesel engine testers (DETs) and 126 non-DETs with the aim of identifying evidence of increased risk for cardiovascular diseases. Environmental monitoring suggested that DETs were exposed to high levels of diesel exhaust aerosol (282.3 μg/m3 PM2.5 and 135.2 μg/m3 elemental carbon). Surprisingly, chronic diesel exhaust exposure was associated with a pro-inflammatory phenotype in the ex vivo endothelial cell model, in a dose-dependent manner with CCL5 and VCAM as most affected genes. This dysfunction was not mediated by reduction in circulatory pro-inflammatory factors but significantly associated with a reduction in circulatory metabolites cGMP and an increase in primary DNA damage in leucocyte in a dose-dependent manner, which also explained a large magnitude of association between diesel exhaust exposure and ex vivo endothelial biosensor response. Exogenous cGMP addition experiment further confirmed the induction of ex vivo biosensor gene expressions in endothelial cells treated with physiologically relevant levels of metabolites cGMP.ConclusionSerum-borne bioactivity caused the arterial endothelial cell dysfunction may attribute to the circulatory metabolites based on the ex vivo biosensor assay. The reduced cGMP and increased polycyclic aromatic hydrocarbons metabolites-induced cyto/geno-toxic play important role in the endothelial cell dysfunction of workers chronic exposure to diesel exhaust.

Sildenafil prevents right ventricular hypertrophy and improves heart rate variability in rats with pulmonary hypertension secondary to experimental diabetes

ABSTRACT Chronic treatment with sildenafil (SILD) is an effective protector on the development of cardiovascular complications of pulmonary hypertension (PH) and diabetes. However, to date, no studies have evaluated the effect of SILD on cardiopulmonary pathophysiology during PH secondary to type 1 diabetes. Aim: The present study aimed to evaluate the beneficial effects of chronic SILD treatment on pulmonary arterial pressure, right ventricular hypertrophy (RVH) and cardiac autonomic dysfunction in rats with PH secondary to diabetes. Metodology: Male Sprague Dawley rats were randomly distributed into the control group (saline), diabetic group (60 mg/kg with streptozotocin), SILD-treated control group (20 mg/kg) and SILD-treated diabetic group. Results: After 8 weeks the type 1 diabetic animals presented PH, endothelial dysfunction of the pulmonary arteries, electrocardiographic alterations, RVH and overexpression of phosphodiesterase type 5 in the heart. In type 1 diabetic animals, SILD treatment prevented the development of PH, endothelial dysfunction and RVH. SILD treatment also prevented alterations in the corrected QT period and heart rate variability and prevented overexpression of phosphodiesterase type 5. Conclusion: Our results indicate for the first time that SILD treatment prevents pulmonary arterial endothelial dysfunction, pulmonary hypertension, right ventricular hypertrophy and improves heart rate variability in type 1 diabetic rats.

Influence of Apnea Hypopnea Index and the Degree of Airflow Limitation on Endothelial Function in Patients Undergoing Diagnostic Coronary Angiography.

Simple SummaryObstructive sleep apnea and airflow limitation disorders are linked to increased cardiovascular morbidity and mortality in patients with chronic coronary syndrome. Although the exact mechanism associated with this phenomenon remains poorly elucidated, the impairment of endothelial function observed in both breathing disorders and cardiovascular disease is one of the possible pathophysiological processes linking those conditions. In the present study, we sought to determine the possible relationship between the endothelial function, signs of disturbed respiration during sleep, and airflow limitation in chronic coronary syndrome patients undergoing diagnostic invasive coronary angiography. Our study showed that obstructive sleep apnea signs measured by WatchPAT (respiratory disturbance index, apnea and hypopnea index, and oxygen desaturation index) were associated with endothelial dysfunction. Additionally, greater airflow limitation by spirometry was detected in patients with endothelial dysfunction. Patients with endothelial dysfunction showed an increase in left ventricular hypertrophy with a trend of increase in left atrial enlargement, indicating underlying diastolic dysfunction. However, the endothelial dysfunction was independent of the presence or severity of obstructive coronary artery disease in coronary angiography. We believe that our study may complement and extend the current understanding of endothelial dysfunction in the mechanism, explaining the relationship between sleep apnea and cardiovascular diseases.Background: Obstructive sleep apnea is associated with an increased prevalence of cardiovascular disease. The mechanism of these associations is not completely understood. We aimed to investigate the association of the apnea hypopnea index and the degree of airflow limitation with endothelial dysfunction. Methods: This was a single-center prospective study of patients admitted for diagnostic coronary angiography (CAG). Endothelial function was assessed by the non-invasive EndoPAT system by reactive hyperemia index (RHI) and divided into two groups: endothelial dysfunction and normal endothelial function. Sleep apnea signs were detected by WatchPAT measuring the respiratory disturbance index (pRDI), the apnea and hypopnea index (pAHI), and the oxygen desaturation index (ODI). Patients underwent spirometry and body plethysmography. Based on CAG, the severity of coronary artery disease was assessed as follows: no significant coronary artery disease, single-, two- and three-vessel disease. Results: A total of 113 patients were included in the study. Breathing disorders measured by WatchPAT and spirometry were more severe in patients with endothelial dysfunction: pRDI (27.3 vs. 14.8, p = 0.001), pAHI (24.6 vs. 10.3, p < 0.001), ODI (13.7 vs. 5.2, p = 0.002), forced expiratory volume in one second (FEV1) (81.2 vs. 89, p = 0.05). In a multivariate regression analysis, pAHI and FEV1 were independent predictors of endothelial dysfunction assessed by RHI. There was no correlation between the severity of coronary artery disease and endothelial dysfunction. Conclusions: Obstructive sleep apnea signs and greater airflow limitation were associated with endothelial dysfunction regardless of the severity of the coronary artery disease.

Thromboxane-dependent coronary vasoconstriction in obese mice: Role of peroxynitrite

Obesity leads to chronic oxidative stress promoting the development of cardiovascular diseases including coronary artery disease and endothelial dysfunction. Increased reactive oxygen species production associated with obesity might lead to endothelial dysfunction through cyclooxygenase (COX) pathway. We evaluated arachidonic acid (AA)-dependent coronary vascular responses and explored COX metabolism in obese C57BL/6 mice. In response to arachidonic acid (AA), isolated hearts from obese mice showed increased vasoconstriction compared with control mice. Released thromboxane (TX) A2 during AA-induced vasoconstriction phase was increased in heart perfusates from obese mice. Indomethacin and 1-benzylimidazole, both reduced vasoconstriction response in control and obese mice. Vasoconstriction response to TXA2 mimetic analog U46619 was 2.7 higher in obese mice. Obesity increased COX-2, TXS and TX receptor protein expression as well as oxidative stress evaluated by nitrotyrosine and peroxynitrite levels, compared with control mice. Obese mice treated with FeTMPyP, a peroxynitrite scavenger, reversed all these parameters to control levels. These data suggest that alterations in COX pathway may be associated with increased generation of free radicals, including peroxynitrite, that result from the oxidative stress observed in obesity.

The relationship of endothelial function and arterial stiffness with subclinical target organ damage in essential hypertension.

This study aimed to explore whether brachial‐ankle pulse wave velocity (baPWV) and brachial artery flow‐mediated dilation (FMD) or the interaction of both parameters are associated with subclinical target organ damage (STOD) indices in patients with essential hypertension. A total of 4618 patients registered from January 2015 to October 2020 were included. baPWV and FMD were measured to evaluate arterial stiffness and endothelial dysfunction. Whereas left ventricular hypertrophy (LVH), urine albumin‐creatinine ratio (UACR), and carotid intima‐media thickness (CIMT) were obtained as STOD indicators. On multivariable logistic regression analysis with potential confounders, higher quartiles of baPWV and FMD were significantly associated with an increased risk of STOD. In patients <65 years of age, the odds ratio (OR) of LVH, UACR, and CIMT ≥.9 mm for the fourth versus the first quartile of baPWV were 1.765 (1.390–2.240), 2.832 (2.014–3.813), and 3.075 (2.315–4.084), respectively. In interaction analysis, an increase in baPWV shows a progressively higher risk of STOD across the quartiles of FMD. Also, the estimated absolute risks of LVH, UACR, and CIMT ≥.9 mm for the first to fourth quartile of baPWV increased from 1.88 to 2.75, 2.35 to 4.44, and 3.10 to 6.10, respectively, in patients grouped by FMD quartiles. The addition of baPWV to FMD slightly improved risk prediction for STOD. BaPWV and FMD were independently associated with an increased risk of STOD in patients with essential hypertension especially among patients <65 years of age. Patients with elevated baPWV and decreased FMD parameters are at increased risk of STOD.

Vascular Function and Frailty in Community-Dwelling Older Individuals

BackgroundFrailty is a condition characterized by a state of reduced physiological reserve and increased vulnerability to stressors. Frail individuals have a higher likelihood of developing cardiovascular disease (CVD). However, the mechanisms underlying the association between frailty and CVD remain unclear.ObjectivesThis study investigated whether frailty is associated with vascular function in community-dwelling older individuals.Material and MethodsWe conducted a cross-sectional analysis of 92 community-dwelling individuals aged ≥ 65 years, including 30 non-frail, 43 pre-frail, 19 frail individuals. Vascular function was assessed by brachial-ankle pulse wave velocity (PWV, measuring arterial stiffness) and flow-mediated dilation of the brachial artery (FMD, measuring endothelial function).ResultsThe PWV was significantly higher in both pre-frail and frail groups than in the non-frail group (non-frail: 1615.7 ± 209.9 cm/s vs. pre-frail: 1815.2 ± 265.0 cm/s vs. frail: 1829.9 ± 256.0 cm/s, respectively, p = 0.003). The FMD was significantly lower in both pre-frail and frail groups than in the non-frail group (non-frail: 5.1 ± 2.1% vs. pre-frail: 3.4 ± 1.3% vs. frail: 3.1 ± 1.2% cm/s, respectively, p = 0.001). Multiple logistic regression analyses indicated that pre-frail and frail group were associated with arterial stiffness (OR, 2.92; 95% CI, 1.01–8.42; OR, 3.56; 95% CI, 0.85–14.91) and endothelial dysfunction (OR, 2.17; 95% CI, 0.41–3.09; OR, 2.27; 95% CI, 0.31–6.97).ConclusionsThus, pre-frailty and frailty are associated with impaired vascular function in community-dwelling older adults, even when adjusting for confounding factors. These findings may help to prevent the potential consequences between CVD and frailty in community-dwelling older individuals.

Dietary Blueberry Ameliorates Vascular Complications in Diabetic Mice Possibly through NOX4 and Modulates Composition and Functional Diversity of Gut Microbes.

In diabetes, endothelial inflammation and dysfunction play a pivotal role in the development of vascular disease. This study investigates the effect of dietary blueberries on vascular complications and gut microbiome in diabetic mice. Seven-week-old diabetic db/db mice consume a standard diet (db/db) or a diet supplemented with 3.8% freeze-dried blueberry (db/db+BB) for 10 weeks. Control db/+ mice are fed a standard diet (db/+). Vascular inflammation is assessed by measuring monocyte binding to vasculature and inflammatory markers. Isometric tension procedures are used to assess mesenteric artery function. db/db mice exhibit enhanced vascular inflammation and reduced endothelial-dependent vasorelaxation as compared to db/+ mice, but these are improved in db/db+BB mice. Blueberry supplementation reduces the expression of NOX4 and IκKβ in the aortic vessel and vascular endothelial cells (ECs) isolated from db/db+BB compared to db/db mice. The blueberry metabolites serum reduces glucose and palmitate induced endothelial inflammation in mouse aortic ECs. Further, blueberry supplementation increases commensal microbes and modulates the functional potential of gut microbes in diabetic mice. Dietary blueberry suppresses vascular inflammation, attenuates arterial endothelial dysfunction, and supports the growth of commensal microbes in diabetic mice. The endothelial-specific vascular benefits of blueberries are mediated through NOX4 signaling.

Bibliometric analysis of the inflammatory mechanism in aortic disease.

In view of the key role of inflammation in the pathogenesis of aortic disease, we visually analyzed the research hotspots of inflammatory mechanism in aortic disease in this work through the method of bibliometrics from the Web of Science (WOS) Core database over the past three decades. A visual bibliometric network of research articles on inflammatory mechanisms in aortic disease was obtained from VOSviewer and Citespace based on the WOS Core Collection. A total of 1278 documents from January 1990 to February 2021 were selected for analysis. The United States and China had the highest percentage of articles, comprising 34.01% and 24.92% of articles worldwide, respectively. Harvard University has published the most articles in this field, followed by the University of Michigan and Huazhong University of Science and Technology. The top 3 research hotspots were atherosclerosis, oxidative stress, and macrophages. The journal with the most articles in this area was Arteriosclerosis Thrombosis and Vascular Biology, followed by Atherosclerosis and PLOS One. The research trend on inflammatory mechanisms in the aortic system has 5 distinct directions: (1) atherosclerosis, NF-κB, expression, smooth muscle cell, and oxidative stress; (2) coronary artery disease, C-reactive protein, risk factors, endothelial dysfunction, and aortic stenosis; (3) abdominal aortic aneurysm, matrix metalloproteinases, macrophage, and pathogenesis; (4) cholesterol, metabolism, low-density lipoprotein, gene expression, and a therosclerotic lesions; and (5) calcific aortic valve disease, interstitial cells, calcification, and stenosis. Inflammatory mechanism research has shown a tendency to rise gradually in the aortic field. Numerous studies have explored the role of inflammatory responses in aortic disease, which may increase the risk of endothelial dysfunction (aortic fibrosis and stiffness) and induce plaque formation. Among them, NFκB activation, nitric-oxide synthase expression, and oxidative stress are particularly essential.

Is atherosklerosi̇s developing risk in patients with asthma?

Asthma is an inflammatory disease of the airways and is characterized by attacks of bronchospasm. Atherosclerosis develops as a result of a series of systemic inflammatory processes that begin with arterial endothelial dysfunction. Arteries tend to dilate in hypoxemic conditions Flow-Mediated Dilation (FMD) is a non-invasive, low-cost, straightforward and effective method that was described some 20 years ago, showing endothelial function and therefore a predisposition to atherosclerosis, according to the reflex vasodilation response of the artery after occlusion. In this study, we aimed to evaluate the susceptibility of these patients to atherosclerosis by performing the FMD test in controlled and uncontrolled asthma groups. We included 61 asthma patients in this study and 30 healthy people enrolled thi study as control group. Thirty-two of the patients were uncontrolled, did not receive regular treatment and were not followed up regularly, whereas 29 patients were full symptom control. Pulmonary function tests were performed on all subjects who met the inclusion criteria of the study and gave informed consent. After the pulmonary function test, the right brachial artery diameters of all cases were measured from intima to intima by Doppler USG. FEV1 values were 67.28±9.89% in in patients with uncontrolled astma, and 79±7 in symptom free group of astma patients. The initial brachial artery diameter was 4.40±0.33 and The measurement made after 5 minutes was 4.69±0.296 (p&lt;0.001) in patients with uncontrolled astmatic patents. The difference between these two measurements was 0.29±0.16. FMD tet results in Symptom free patients values were 4.45±03 and 4.81±0.4 respectively (p&lt;0.001). Initial and after measurements difference between symptom free and uncontrolled patients were 0.36±0.16 and 0.29±0.11 p&lt;0.01. There was not statistically significant difference between symptom free patients and healthy group. We have shown that vascular disfunction in symptomatic astma patients with FMD test. Atherosclerosis developing might be higher in asthma patients and this patients should be encourage to regular medicine usage.

On the Question of the Reflexotherapy Action Mechanisms in the Ischemic Stroke Acute Period (Literature Review)

A high degree of disability in stroke patients, along with severe social and economic losses, determine the enduring urgency of the problem of early rehabilitation for post-stroke patients. Despite the proven effectiveness of the various reflexotherapy techniques in rehabilitation of patients with ischemic stroke, the underlying mechanisms remain unclear. The aim of the review was to analyze the mechanisms of the acupuncture intervention effect on the main links of the ischemic stroke pathogenesis, on neurological deficit and the volume of cerebral infarction (based on publications in international databases). The use of acupuncture in the acute period of ischemic stroke can improve the ability to cerebrovascular reserve, reduce the severity of arterial stiffness and endothelial dysfunction, induce neuroprotection, inhibit cell apoptosis and stimulate neuroplasticity, alleviate the inflammatory response in acute cerebral ischemia, regulate mediators of inflammation and oxidative stress etc., thus improving cerebral blood flow. The analysis of literature data has shown that acupuncture induces multilevel regulation through complex mechanisms, and one factor may not be enough to explain the positive effect against cerebral ischemia.

AT2R stimulation with C21 prevents arterial stiffening and endothelial dysfunction in the abdominal aorta from mice fed a high-fat diet.

The aim of the present study was to evaluate the effect of Compound 21 (C21), a selective AT2R agonist, on the prevention of endothelial dysfunction, extracellular matrix (ECM) remodeling and arterial stiffness associated with diet-induced obesity (DIO). Five-week-old male C57BL/6J mice were fed a standard (Chow) or high-fat diet (HF) for 6 weeks. Half of the animals of each group were simultaneously treated with C21 (1 mg/kg/day, in the drinking water), generating four groups: Chow C, Chow C21, HF C, and HF C21. Vascular function and mechanical properties were determined in the abdominal aorta. To evaluate ECM remodeling, collagen deposition and TGF-β1 concentrations were determined in the abdominal aorta and the activity of metalloproteinases (MMP) 2 and 9 was analyzed in the plasma. Abdominal aortas from HF C mice showed endothelial dysfunction as well as enhanced contractile but reduced relaxant responses to Ang II. This effect was abrogated with C21 treatment by preserving NO availability. A left-shift in the tension-stretch relationship, paralleled by an augmented β-index (marker of intrinsic arterial stiffness), and enhanced collagen deposition and MMP-2/-9 activities were also detected in HF mice. However, when treated with C21, HF mice exhibited lower TGF-β1 levels in abdominal aortas together with reduced MMP activities and collagen deposition compared with HF C mice. In conclusion, these data demonstrate that AT2R stimulation by C21 in obesity preserves NO availability and prevents unhealthy vascular remodeling, thus protecting the abdominal aorta in HF mice against the development of endothelial dysfunction, ECM remodeling and arterial stiffness.

Nitric oxide-dependent micro- and macrovascular dysfunction occurs early in adolescents with type 1 diabetes.

Arterial stiffness and endothelial dysfunction are both reported in children with type 1 diabetes (DM1) and may predict future cardiovascular events. In health, nitric oxide (NO) relaxes arteries and increases microvascular perfusion. The relationships between NO-dependent macro- and microvascular functional responses and arterial stiffness have not been studied in adolescents with DM1. Here, we assessed macro- and microvascular function in DM1 adolescents and age-matched controls at baseline and during an oral glucose challenge (OGTT). DM1 adolescents (n = 16) and controls (n = 14) were studied before and during an OGTT. At baseline, we measured: 1) large artery stiffness using both aortic augmentation index (AI) and carotid-femoral pulse wave velocity (cfPWV); 2) brachial flow-mediated dilation (FMD) and forearm endothelial function using postischemic flow velocity (PIFV); and 3) forearm muscle microvascular blood volume (MBV) using contrast-enhanced ultrasound. Following OGTT, AI, cfPWV, and MBV were reassessed at 60 min and MBV again at 120 min. Within individual and between-group, comparisons were made by paired and unpaired t tests or repeated measures ANOVA. Baseline FMD was lower (P = 0.02) in DM1. PWV at 0 and 60 min did not differ between groups. Baseline AI did not differ between groups but declined with OGTT only in controls (P = 0.02) and was lower than DM1 at 60 min (P < 0.03). Baseline MBV was comparable in DM1 and control groups, but declined in DM1 at 120 min (P = 0.01) and was lower than the control group (P < 0.03). There was an inverse correlation between plasma glucose and MBV at 120 min (r = -0.523, P < 0.01). No differences were noted between groups for V̇O2max (mL/min/kg), body fat (%), or body mass index (BMI). NO-dependent macro- and microvascular function, including FMD and AI, and microvascular perfusion, respectively, are impaired early in the course of DM1, precede increases of arterial stiffness, and may provide an early indicator of vascular risk.NEW & NOTEWORTHY This is the first study to show that type 1 diabetes impairs multiple nitric oxide-dependent vascular functions.