Despite growing evidence of the significant influence of blood-flow-restricted (BFR) training on different body functions, its impact on the vascular system, especially the arteries, is controversial. Therefore, the objective of our study was to analyze how BFR exercise, compared to other types of exercise without the restriction of blood flow, influences arterial functions and angiogenesis in adults. Studies comparing the effect of BFR versus non-BFR training on arterial parameters were divided into three categories: endothelial function, angiogenesis, and other vasculature functions. The search was based on Cochrane Library, PubMed®, and Embase, and 38 studies were included. The meta-analysis revealed a more significant improvement in flow-mediated dilatation (FMD) (p = 0.002) and the production of the primary angiogenesis biomarker vascular endothelial growth factor (VEGF) (p = 0.009) after BFR compared to non-BFR training (p = 0.002). The analysis of the pulse wave velocity, ankle-brachial index, systolic blood pressure, and heart rate did not show significant differences in changes between BFR and non-BFR training. The other parameters examined did not have sufficient data to be included in the meta-analysis. The results obtained present trends that suggest significant impacts of BFR training on endothelial functions and angiogenesis. There is still a lack of multicenter randomized clinical trials including many participants, and such studies are necessary to confirm the advantage of BFR over non-BFR activity.

Blood-flow-restricted exercise (BFRE) has been gaining constantly increasing interest in rehabilitation, but its influence on endothelial functions has not been well studied yet. Our aim is to examine the influence of low-resistance BFRE on endothelial functions and angiogenesis. This prospective cross-over study involved 35 young healthy adults. They conducted a 21-min low-resistant exercise with blood flow restricted by pressure cuffs placed on arms and tights. They also did the same training but without blood flow restriction. Endothelial parameters and angiogenesis biomarkers were evaluated before and up to 20 min after exercise. Both types of exercise increased Flow-Mediated Dilatation (FMD) but elevation after BFRE was more significant compared to the controls. The stiffness index decreased only after BFRE, while the reflection index decreased significantly after both types of exercise but was higher after BFRE. Platelet endothelial cell adhesion molecule (PECAM-1) and vascular endothelial growth factor receptor 2 (VEGFR-2) concentrations were increased by both exercise types but elevations were higher after BFRE compared to the controls. Only BFRE elevated the mean serum CD34 protein concentration. Based on these results, we can assume that low-resistance BFR exercise stimulates angiogenesis and improves endothelial functions more significantly compared to the same training performed without blood flow restriction.

Background: Endothelial dysfunction defines outcomes and serves as a surrogate parameter for the progression of cardiovascular disease. For symptomatic peripheral artery disease (PAD) endovascular treatment is the primary revascularization strategy, which affects endothelial function. Interventional mechanical atherothrombectomy (MATH) provides advantages when treating complex atherosclerotic and thrombotic lesions. We now aimed to determine the impact and mechanisms of MATH on endothelial function. Patients and methods: Endothelial function was determined using flow-mediated dilation (FMD) before and after lower limb intervention with a six-month follow-up in the target and control vessel in 15 PAD MATH+DCB treated patients and compared to 15 non-Math controls. In a further cohort of 20 patients the impact of MATH and DCB on vascular structure and virtual histology was assessed through intravascular ultrasound (IVUS) and compared to DCB treatment alone. Results: Improved endothelial function after 6 months was observed in both groups for the target and nontarget vessel. When comparing the changes from baseline endothelial function, treatment with MATH+DCB was superior to DCB treatment in the target vessel. IVUS revealed a greater improvement in luminal area and plaque burden reduction after MATH treatment. Virtual histology disclosed MATH-associated changes in plaque composition evidenced by alterations in fibrous volume and reductions in superficial calcium. Conclusions: We demonstrate an improved endothelial function after MATH treatment as compared to DCB treatment. The improved vessel function is evidenced by MATH-related plaque burden reduction, improved luminal gain and a decrease in superficial calcification. Clinicaltrials.gov: NCT04092972.

Previous studies have shown that female offspring are resistant to fetal high-fat diet (HFD)-induced programming of heightened vascular contraction; however, the underlying mechanisms remain unclear. The present study tested the hypothesis that estrogen plays a key role in protecting females from fetal programming of increased vascular contraction induced by maternal HFD exposure. Pregnant rats were fed a normal diet (ND) or HFD (60% kcal from fat). Ovariectomy (OVX) and 17β-estradiol (E2) replacement were performed on 8-week-old female offspring. Aortas were isolated from adult female offspring. Maternal HFD exposure increased angiotensin II (Ang II)-induced contractions of the aorta in adult OVX offspring, which was abrogated by E2 replacement. The AT1 receptor (AT1R) antagonist losartan (10 μM), but not the AT2 receptor (AT2R) antagonist PD123319 (10 μM), completely blocked Ang II-induced contractions in both ND and HFD offspring. In addition, HFD exposure caused a decrease in endothelium-dependent relaxations induced by acetylcholine (ACh) in adult OVX but not OVX-E2 offspring. However, it had no effect on sodium nitroprusside (SNP)-induced endothelium-independent aorta relaxation in any of the six groups. Maternal HFD feeding increased AT1R, but not AT2R, leading to an increased AT1R/AT2R ratio in HFD-exposed OVX offspring, associated with selective decreases in DNA methylation at the AT1aR promoter, which was ameliorated by E2 replacement. Our results indicated that estrogen play a key role in sex differences of maternal HFD-induced vascular dysfunction and development of hypertensive phenotype in adulthood by differently regulating vascular AT1R and AT2R gene expression through a DNA methylation mechanism.

Background: Treatment of symptomatic peripheral artery disease (PAD) through endovascular interventions is the primary revascularization strategy. Interventions restore perfusion but may cause severe injury to the vascular endothelium, which regulates vascular tone. Endothelial dysfunction is involved in the progression of cardiovascular disease, with higher incidences of vascular events. We aimed to determine the impact of percutaneous interventions on change in endothelial function. Patients and methods: Endothelial function was determined using flow-mediated dilation (FMD) before, the day after lower limb intervention with paclitaxel-coated balloons or stent guided interventions and after a six-month follow-up in the target limb, control limb and the systemic circulation in 42 PAD patients aged 70.2±9 years and 66% men. Additionally, macro- and microvascular function were assessed. Results: In PAD patients aged 70.2±9 years and 66% men, we observed an immediate enhancement of macro-, microvascular and endothelial function after endovascular treatment (FMD of superficial femoral artery (SFA) 3.7±0.2% to 4.1±0.1%, n=42, p=0.02), a sustained long-term improvement after 6-months (FMD SFA 3.7±0.2% to 4.2±0.1%, n=42, p=0.01), and moreover an improved systemic endothelial function (FMD brachial artery 4.3±0.1% to 4.7±0.2, n=42, p=0.01) following peripheral interventions. Subgroup analysis however revealed that following paclitaxel-based percutaneous intervention, the paclitaxel dosage applied was inversely related to the chronic improvement in local endothelial function (r=-0.6, n=22, p=0.005) without evidence for systemic effects (r=-0.25, p=0.27). Conclusions: We demonstrate an improved local and systemic endothelial function after treatment of atherosclerotic peripheral disease with a distinguished response after endovascular intervention with higher dosage of applied paclitaxel restraining the benefits. Further studies have to determine the optimal interventional strategy with respect to different treatment modalities to maintain vessel functions.

A maternal high-fat diet (HFD) is a risk factor for cardiovascular diseases in offspring. The aim of the study was to determine whether maternal HFD causes the epigenetic programming of vascular angiotensin II receptors (ATRs) and leads to heightened vascular contraction in adult male offspring in a sex-dependent manner. Pregnant rats were treated with HFD (60% kcal fat). Aortas were isolated from adult male and female offspring. Maternal HFD increased phenylephrine (PE)-and angiotensin II (Ang II)-induced contractions of the aorta in male but not female offspring. NG-nitro-L-arginine (ʟ-NNA; 100 μM) abrogated the maternal HFD-induced increase in PE-mediated contraction. HFD caused a decrease in endothelium-dependent relaxations induced by acetylcholine in male but not female offspring. However, it had no effect on sodium nitroprusside-induced endothelium-independent relaxations of aortas regardless of sex. The AT1 receptor (AT1R) antagonist losartan (10 μM), but not the AT2 receptor (AT2R) antagonist PD123319 (10 μM), blocked Ang II-induced contractions in both control and HFD offspring in both sexes. Maternal HFD increased AT1R but decreased AT2R, leading to an increased ratio of AT1R/AT2R in HFD male offspring, which was associated with selective decreases in DNA methylation at the AT1aR promoter and increases in DNA methylation at the AT2R promoter. The vascular ratio of AT1R/AT2R was not significantly different in HFD female offspring compared with the control group. Our results indicated that maternal HFD caused a differential regulation of vascular AT1R and AT2R gene expression through a DNA methylation mechanism, which may be involved in HFD-induced vascular dysfunction and the development of a hypertensive phenotype in adulthood in a sex-dependent manner.

The preventive efficacies and safety of Emblica Officinalis Gatertn (Amla), a most important and extensively studied plant in the traditional Indian Ayurvedic system of medicine, are presented. Eligible healthy adult subjects (n = 15) were randomized to receive either amla or placebo (500 mg per day) during an 18-week study. The efficacy parameters evaluated were the vascular function, blood hematology, oxidative and inflammatory biomarkers, glucose and lipid profiles, urinalysis, and liver hepatotoxicity. The amla intake showed significant improvements in the primary efficacy parameter of blood fluidity. There were also improvements in the secondary endpoints including lowering of von Willebrand factor (vWF), reduced 8-hydroxy-2\'-deoxyguanosine (8-OHdG) as well as thrombin (TM) biomarkers of oxidative stress along with a significant improvement in HDL-cholesterol and lowering the LDL-cholesterol levels. No substantial changes were observed in liver hepatotoxicity, urinalysis, and hematology after consumption of amla compared to baseline or placebo. In addition, no adverse events, changes safety parameters or tolerance issues were observed after consumption of amla. In conclusion, amla supplementation showed acceptable palatability, improved endothelial functions and reduced oxidative stress.

OBJECTIVE: To evaluate the temporal profile of arterial functions during the course of pregnancy and also to determine the predictive accuracy of vascular function indices in development of preeclampsia (PE).
METHODS: Longitudinal study, two hundred and eight women participated in the study and vascular functions were assessed at 11-13, 20-22 and 30-32 weeks of gestation.
METHODS: Flow mediated dilatation (FMD), augmentation index (AIx), pulse wave velocity (PWV).
RESULTS: Out of 208 women, 13 women developed PE while 70 remained healthy pregnant (HP). In HP women, normalized FMD decreased gradually from 11 to 13 weeks to 30-32 weeks of gestation (p < 0.05). While in PE, Normalized FMD decreased from 11 to 13 to 20-22 weeks of gestation (p < 0.05) and was significantly lower in PE than HP group at 20-22 weeks of gestation (p < 0.05). AIx showed a mid trimester drop in HP group (p < 0.05) while demonstrated a rising trend in PE. Both AIx and PWV were significantly higher in PE than HP group during the course of pregnancy (p < 0.05). AIx demonstrated good sensitivity and specificity at both 11-13 and 20-22 weeks of gestation. Carotid femoral PWV showed an area under curve (AUC) of 78.18% and 69.75% at 11-13 and 20-22 weeks of gestation respectively. Carotid radial PWV showed good accuracy at 20-22 weeks (AUC-77.58%) of gestation.
CONCLUSIONS: Compromised arterial functions precede the onset of PE. AIx and carotid femoral PWV constitute potential predictive marker in early pregnancy for later development of PE.

BACKGROUND: Long-term exercise training may have negative effects on cardiovascular functions. Measurement and calculation of central hemodynamic parameters can comprehensively evaluate the cardiovascular functions. This study aims to compare the central hemodynamics between young basketball athletes and matched controls.
METHODS: Total 19 young long-term trained male basketball athletes and 17 matched male recreationally active controls participated. The central hemodynamic parameters such as central blood pressure, pulse pressure, heart rate (HR), augmentation index normalised to 75 bpm (AIx@HR75), augmentation index (AIx), ejection duration (ED), sub-endocardial viability ratio (SEVR) were measured, and total peripheral resistance (TPR), stroke volume (SV) and cardiac output (CO) were calculated. Non-parameter tests and t-test were used to analyse the central hemodynamic parameters between athletes and controls.
RESULTS: HR (56 ± 5 bpm versus 79 ± 9 bpm, p < .001), AIx@HR75 (-8 ± 10% versus -1 ± 10%, p < .05), ED (28 ± 2% versus 36 ± 3%, p < .001) and TPR (0.004 ± 0.006 mmHg s/mL versus 0.012 ± 0.006 mmHg s/mL, p < .001) were significantly lower in basketball athletes compared to the controls. SEVR (231 ± 32% versus 159 ± 21%, p < .001) and SV (154 ± 50 mL versus 101 ± 43 mL, p < .01) were significantly higher in basketball athletes than those in the controls. However, there were no significant differences in central blood pressure, pulse pressure, AIx and CO between them.
CONCLUSIONS: There is no negative effect on central hemodynamics in young basketball athletes after long-term exercise training. The young basketball athletes have a higher myocardial perfusion, higher efficiency of blood supply, stronger vascular functions and better balance of myocardial oxygen of supply and demand than the controls in this central hemodynamic parameters analysis.

OBJECTIVE: Hemodialysis (HD) per se entails vascular dysfunction in patients with ESRD. Endothelial dysfunction is a key step in atherosclerosis and is characterized by impaired flow-mediated dilation (FMD). Interventional studies have shown that cocoa flavanol (CF)-rich supplements improve vascular function. Aim of this study was to investigate the effect of flavanol-rich bioactive food ingredients on acute and chronic HD-induced vascular dysfunction in ESRD.
METHODS: We conducted a randomized, double-blind, placebo-controlled trial from 2012 to 2013. Fifty-seven participants were enrolled, ingested CF-rich beverages (900 mg CF per study day), and were compared with those ingesting CF-free placebo. This included (1) a baseline cross-over acute study to determine safety and efficacy of CF and (2) a subsequent chronic parallel group study with a 30-day follow-up period to study effects of CF on HD-mediated vascular dysfunction entailing (3) an acute substudy during HD in flavanol-naive patients and (4) an acute on chronic study during HD. Primary and secondary outcome measures included changes in FMD and hemodynamics.
RESULTS: CF ingestion was well tolerated. Acute ingestion improved FMD by 53% (3.2±0.6% to 4.8±0.9% versus placebo, 3.2±0.7% to 3.3±0.8%; P<0.001), with no effects on BP or heart rate. A 30-day ingestion of CF led to an increase in baseline FMD by 18% (3.4±0.9% to 3.9±0.8% versus placebo, 3.5±0.7% to 3.5±0.7%; P<0.001), with reduced diastolic BP (73±12 to 69±11 mmHg versus placebo, 70±11 to 73±13 mmHg; P=0.03) and increased heart rate (70±12 to 74±13 bpm versus placebo, 75±15 to 74±13 bpm; P=0.01). No effects were observed for placebo. Acute ingestion of CF during HD alleviated HD-induced vascular dysfunction (3.4±0.9% to 2.7±0.6% versus placebo, 3.5±0.7% to 2.0±0.6%; P<0.001). This effect was sustained throughout the study (acute on chronic, 3.9±0.9% to 3.0±0.7% versus placebo, 3.5±0.7% to 2.2±0.6; P=0.01).
CONCLUSIONS: Dietary CF ingestion mitigates acute HD-induced and chronic endothelial dysfunction in patients with ESRD and thus, improves vascular function in this high-risk population. Larger clinical trials are warranted to test whether this translates into an improved cardiovascular prognosis in patients with ESRD.