Effectiveness of high intensity interval training on cardiorespiratory fitness and endothelial function in type 2 diabetes:A systematic review

BACKGROUND Type 2 diabetes mellitus(T2DM)is a chronic metabolic syndrome characterized by insulin resistance and hyperglycemia that may lead to endothelial dysfunction,reduced functional capacity and exercise intolerance.Regular aerobic exercise has been promoted as the most beneficial non-pharmacological treatment of cardiovascular diseases.High intensity interval training(HIIT)seems to be superior than moderate-intensity continuous training(MICT)in cardiovascular diseases by improving brachial artery flow-mediated dilation(FMD)and cardiorespiratory fitness to a greater extent.However,the beneficial effects of HIIT in patients with T2DM still remain under investigation and number of studies is limited.AIM To evaluate the effectiveness of high intensity interval training on cardiorespiratory fitness and endothelial function in patients with T2DM.METHODS We performed a search on PubMed,PEDro and CINAHL databases,selecting papers published between December 2012 and December 2022 and identified published randomized controlled trials(RCTs)in the English language that included community or outpatient exercise training programs in patients with T2DM.RCTs were assessed for methodological rigor and risk of bias via the Physiotherapy Evidence Database(PEDro).The primary outcome was peak VO_(2 ) and the secondary outcome was endothelial function assessed either by FMD or other indices of microcirculation.RESULTS Twelve studies were included in our systematic review.The 12 RCTs resulted in 661 participants in total.HIIT was performed in 310 patients(46.8%),MICT to 271 and the rest 80 belonged to the control group.Peak VO_(2 ) increased in 10 out of 12 studies after HIIT.Ten studies compared HIIT with other exercise regimens(MICT or strength endurance)and 4 of them demonstrated additional beneficial effects of HIIT over MICT or other exercise regimens.Moreover,4 studies explored the effects of HIIT on endothelial function and FMD in T2DM patients.In 2 of them,HIIT further improved endothelial function compared to MICT and/or the control group while in the rest 2 studies no differences between HIIT and MICT were observed.CONCLUSION Regular aerobic exercise training has beneficial effects on cardiorespiratory fitness and endothelial function in T2DM patients.HIIT may be superior by improving these parameters to a greater extent than MICT.

Relationship between testosterone and indexes indicating endothelial function in male coronary heart disease patients

Aim： To investigate the relationship between androgen level and the indexes indicating endothelial function in male patients with coronary heart disease （CHD）. Methods： We registered the following data for 106 50-70-year-old men： age, weight, blood lipid, including total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol and triglyceride, whether a smoker, sugar levels, blood pressure, free testosterone （FT）, vascular cell adhesion molecule- 1 （VCAM- 1） and the intima-media thickness （IMT） of common carotid artery, common carotid diameter, maximum velocity in systolic phase, minimum velocity in diastolic phase and resistent index. Among the 106 men, 51 were patients with CHD. The relationships between FT level, VCAM-1 concentration and IMT were examined, respectively, using a stepwise linear regression technique among all the 106 men. Results： There was no statistical difference in terms of age, blood pressure, whether a smoker, sugar levels, HDL-C, minimum velocity in diastolic phase, resistent index between male CHD patients and controls; whereas results for weight, total cholesterol, low density lipoprotein cholesterol, triglyceride, VCAM- 1 and IMT of male CHD patients were higher than those of controls; FT level and maximum velocity in systolic phase were lower. It was found that among all the objects, FT level was inversely correlated with IMT and VCAM-1 concentration. Condusion： FT level was inversely correlated with VCAM-I concentration and IMT which are indicators of endothelial function. （Asian JAndro12008 Mar; 10： 214-218）

Ligliptin for treatment of type 2 diabetes mellitus with early renal injury: Efficacy and impact on endogenous hydrogen sulfide and endothelial function

BACKGROUND Diabetes is a clinically common chronic disease,and its incidence has been increasing in recent years.Diabetes is believed to accelerate the process of atherosclerosis in patients,and abnormal endothelial function is an important factor leading to diabetic kidney damage.AIM To investigate the efficacy of ligliptin in the treatment of type 2 diabetes mellitus(T2DM)with early renal injury and its effect on serum endogenous hydrogen sulfide(H2S),endothelial cell particles,and endothelial function.METHODS From January 2018 to April 2019,110 patients with T2DM and early kidney injury treated at our hospital were divided into an observation group(receiving ligliptin treatment,n=54)and a control group(receiving gliquidone therapy,n=56).Blood glucose and renal function before and after treatment were compared between the two groups.RESULTS The differences in fasting blood glucose,2 h blood glucose,and glycated hemoglobin were not statistically significant between the two groups after treatment.The urinary albumin excretion rate after treatment in the ligliptin group was 70.32±11.21μg/min,which was significantly lower than that of the gliquidone group(P=0.000).Serum endogenous H2S and endothelial cell microparticles of the ligliptin treatment group were 40.04±8.82 mol/L and 133.40±34.39,respectively,which were significantly lower than those of the gliquidone treatment group(P=0.000 for both);endothelin-dependent diastolic function and nitric oxide after treatment in the ligliptin group were 7.98%±1.22%and 190.78±30.32 mol/L,significantly higher than those of the gliquidone treatment group(P=0.000 for both).CONCLUSION Ligliptin treatment of T2DM with early renal injury has the same glucoselowering effect as gliquidone treatment.Ligliptin treatment has a better effect and it can significantly improve the renal function and vascular endothelial function of patients,and reduce serum endogenous H2S and endothelial cell particle levels.

Study on the Effect of Simvastatin on Left Ventricular Mass and Endothelial Function and the Relationship between Their Changes in the Patients with Essential Hypertension

Objective:To study the effect of Simvastatin on the left ventricular mass and endothelial function and to investigate the relationship between their changes in the patients with essential hypertension(EH). Methods: 50 patients with hypertension without severe complication were divided into two groups in a randomized,controlled and single blind trial.Group I(n=25)were given Simvastatin and hydragogue for 12 weeks while Group Ⅱ were given hydragogue during the same time.We detected the left ventricular mass and the brachial artery dilatation induced by reactive hyperemia(DIRH)or nitroglycerin(DING)respectively with ultrasonography in all patients before and after treatment.25 normal subjects without any treatment were taken as the control. Results:The left ventricular mass index(LVMI)was higher in the two groups of patients[(133.61±31.02)g/m 2;(118.04±39.62)g/m 2]than that in the control(88.79±22.73)g/m 2 before treatment(P<0.01,0.000 1,respectively)while the blood pressure was higher.The DIRH was lower in the two groups of patients(5.93±2.24)%;(6.54±3.16)%than that in the control(13.09±2.99)%,P<0.000 1.There was no significantly differences in age,serum concentrations of total cholesterol,triglyceride,sugar,blood pressure or the DING between two groups of patients and the control(P>0.05).And there was no significant difference in the all variables between group Ⅰ and group Ⅱ before treatment.After treatment the LVMI decreased[(133.61±31.02)g/m 2 VS(91.07±16.01)g/m 2,P<0.01]and the DTRH increased[(5.93±2.24)% VS(13.53±2.38)%,P<0.01]in the patients of group Ⅰ while there was no significant change in LVMI and DIRH in the patients of group Ⅱ.The blood pressure in the two groups of patients was decreased to the normal.Compared with group Ⅱ,the changes of LVMI and DIRH was higher in patients of group Ⅰ though the serum concentrations of total cholesterol,triglyceride or sugar were not significantly different.No significant change in serum concentrations oftotal cholesterol,triglyceride or sugar was found during treatment in the two groups of patients.Analysis showed that the LVMI correlated with DIRH and the change of LVMI correlated better with the change of DIRH(r=-0.56;0.69,P<0.000 1,respectly). Conclusions: The increase of left ventricular mass was related with endothelial dysfunction in essential hypertension.Being independent of the changes of serum concentrations of total cholesterol,triglyceride or sugar and blood pressure,Simvastatin could inhibit the increase of left ventricular mass and improve endothelial function.

RELATIONS OF ENDOTHELIAL FUNCTION AND BLOOD FLOW IN BRACHIAL ARTERY AND CORONARY ARTERY

Objective:To determine the relations between endothelium-dependent vasodilator function and blood flow in the brachial and coronary arteries in patients with suspected coronary artery disease.Methods:Twenty-eight patients with suspected coronary artery disease underwent brachial artery endothelial function test by using high-resolution B-mode ultrasound before coronary angiography(CAG)and coronary flow reserve(CFR)test by using intracoronary Doppler technique.The correlation of coronary artery dilatation induced by an increase in blood flow after intracoronary adenosine infusion and brachial artery flow-mediated dilatation(FMD) following reactive hyperemia was evaluated.The relation between the change of brachial artery blood flow and CFR was also studied.Results:There was a positive correlation between brachial FMD and percent change of coronary diameter after adenosine infusion(12.50%±9.35% vs 11.38%±7.55%,r=0.425,P=0.02).There was also a weak negative relation between brachial flow change following reactive hy-peremia and CFR(r=-0.397,P=0.04).Conclusion:There is a correlation between the coronary endo-thelial function and the CFR by ultrasonic determination of brachial flow changes following reactive hyperemia.

Effects of Obstructive Sleep Apneas on Endothelial Function and Autonomic Modulation in Adult Man

Objective To study the effects of obstructive sleep apneas on endothelial function and autonomic modulation. Methods From June 2009 to June 2011, male patients with obstructive sleep apnea hypopnea syndrome (OSAHS) were consecutively enrolled in this study. Patients with an apnea/hypopnea index (AHI) of greater than 15 and without previous treatment for OSAHS were included as Group OSAHS and obese subjects with an AHI of less than 5 were included as non-OSAHS controls (Group Control). Electrocardiography and beat-to-beat blood pressure were continuously recorded from the radial artery by applanation tonometry which was synchronized with polysomnography recording. Endothelial function was measured by arterial augmentation index (AAI). Spectral analysis of heart rate variability (HRV) and blood pressure variability (BPV) were computed for cardiac parasympathetic modulation (high frequency power, HF); sympathetic modulation (low frequency power, LF), sympathovagal balance (LF/HF power of R-R variability, LF/HF) and BPV sympathetic modulation (BPV LF) in normalized units [total power of the components/(total power-very LF power)×100]. Results Finally, 27 moderate-severe OSAHS patients and 22 non-OSAHS obese controls were recruited in the Group OSAHS and Group Control, respectively. In Group OSAHS, the age was 43.3±9.3 year-old, body mass index (BMI) was 36.8±8.7 kg/m 2 ; in Group Control, the age was 42.9±8.6 year-old, BMI was 34.4±7.9 kg/m 2 ; there were no significant differences in age and BMI between the Group OSAHS and Group Control (all P>0.05). The baseline AAI (12.5%±2.2% vs. 8.2%±2.1%) and BPV LF (68.3%±13.5% vs. 61.1%±11.7%) of the Group OSAHS were significantly higher than those of the Group Control (all P<0.05). And after overnight sleep, systolic BP (143.7±14.2 vs. 132.8±13.3 mm Hg), diastolic BP (87.7±7.7 vs. 78.6±5.5 mm Hg), HRV LF (69.7%±14.4% vs. 64.3%±12.1%), HRV LF/HF (3.7±2.0 vs. 2.3±1.3) and BPV LF (77.8%±15.6% vs. 68.3%±13.5%) of the Group OSAHS were significantly increased (all P<0.001), while HRV HF was significantly decreased (21.1%±9.3% vs. 27.5%±10.3%, P<0.05) from baseline.Conclusions The baseline endothelial function and autonomic modulation are impaired in OSAHS patients, which happened prior to hypertension and other cardiovascular complications. And the load effects of overnight obstructive breathing events could induce blood pressure and sympathetic activity increasing in the morning in OSAHS patients without acute aggravation in endothelial dysfunction.

Endothelial Function and Carotid Artery Wall Thickening in Patients with Early Essential Hypertension

To investigate the relationship between endothelial function and carotid artery wall thickening in patients with early mild essential hypertension, the percent dilatation of humerus diameter and intimal-medial thickening (IMT) of common carotid artery was measured by using high-resolution ultrasound in 20 patients with early mild essential hypertension and 18 patients with normotension.The patients with hypertension had not been treated and their history of increased blood pressure was less than 12 months. In essential hypertension group, the percent dilatation of humerus diameter decreased significantly (2. 65 ± 0. 98 % vs6. 38 ± 1. 61 % ) ; IMT of carotid artery increased (0. 88 ± 0. 16mm vs 0. 58 ±0. 08). There was significant negative correlation between IMT and the percentdilatation of humerus diameter (γ= - 0. 82, P<0. 05), and no correlation be-tween IMT and 24 h mean systolic, diastolic pressure (γ= 0. 12 and γ= 0.07,respectively ; P> 0. 05). Our results suggested that there was endothelial dys-function in early mild essential hypertension. Endothelial dysfunction may not on-ly contribute to the pathogenesis of hypertension but also serve as the most impor-tant inducing factor leading trans formation from hypertension to atherosclerosis.

Effects of hormone replacement therapy on endothelial function in menopausal women

Objective To observe the effects of hormone replacement therapy (HRT) on endothelial function in menopausal women. Methods A total of 30 menopausal women were treated with 2.5 mg of Tibolone (Livial) daily. At the same time,30 women with natural menopause without any treatment served as the control group. Endothelium-dependent (EDD),endothelium-independent (NID) vasodilatation function,and estradiol (E2) were examined by the non-invasive high-resolution ultrasonography before the treatment and at 12th,24th,36th and 48th week of treatment,respectively. Results After hormone treatment,E2 increased significantly and EDD was improved significantly (P<0.05),and E2 was positively related with EDD (r=0.8092,P<0.001). No change of EDD was observed in the control group whereas a significant increase was observed in the treatment group. Conclusion Endothelium-dependent vasodilatation dysfunction is prominent in menopausal women. Tibolone can help improve the condition.

Protective effects of sodium ferulate in vascular endothelial function during cardiopulmonary bypass

Objective Cardiopulmonary bypass (CPB) and its related ischemia reperfusion injury may cause endothelial cell injury. To study the protective effects of sodium ferulate in vascular endothelial function during CPB by testing the changes of vascular endothelial cell(CEC) ,nitric oxide(NO) and endothelin-1 (ET-1) in children with congenital heart disease. Methods Sixty patients

Ultrasonic evaluation of the relationship between left ventricular hypertrophy or left ventricular geometry and endothelial function in patients with essential hypertension

Objective： To assess the relationship between left ventricular hypertrophy （LVH） or left ventricular geometry （LVG） and endothelial function in patients with essential hypertension （EH）. Methods： Seventy-six patients and 30 normal subjects were first examined by echocardiography. Brachial artery dilatation induced by reactive hyperemia （DIRH） or nitroglycerin （DING） was detected using high-resolution ultrasonography. Results： DIRH was lower in patients with hypertension than in the controls, and the decrease in DIRH was greater in the patients with LVH than that in patients without LVH （4.36±2.54% vs 8.56 ± 1.87 %; P 〈 0.0001）. There were no significant differences in age, serum concentrations of total cholesterol, triglycerides or sugar, blood pressure and the brachial artery dilatation induced by nitroglycerin between the two groups （P 〉 0.05）. While there was no significant difference in DIRH between the patients with normal left ventricular geometry or cardiac remodeling, the patients showing either eccentric or concentric left ventricular hypertrophy had lower DIRH than the patients with normal left ventricular geometry or cardiac remodeling. The DIRH was the lowest in patients with concentric hypertrophy. Although bivariate analysis showed that the left ventricular mass index （LVMI） correlated well with the brachial artery dilatation induced by reactive hyperemia, diastolic blood pressure and mean blood pressure （r=-0.61, P 〈 0.0001; r=0.27, P 〈 0.05; r=0.31, P 〈 0.05, respectively）, a multivariate stepwise regression demonstrated that LVMI correlated only with the brachial artery dilatation induced by reactive hyperemia. Conclusion： Left ventricular hypertrophy was related to endothelial dysfunction in essential hypertension. The endothelial dysfunction might be basic and important in the progression of left ventricular hypertrophy.

Effects of Exercise Training on Endothelial Function,Arterial Structure,and Physical Conditioning in Patients with Systemic Autoimmune Myopathies:A Case Series Study

Introduction. Exercise training has been effective in improving endothelial function and decreasing arterial stiffness in several systemic autoimmune diseases. However, to date, no studies have assessed patients with systemic autoimmune myopathies (SAM). Methods. Five female patients with definite SAM (3 dermatomyositis and 2 polymyositis) who underwent a 12-week, twice-a-week, exercise training program were assessed prospectively. The following parameters were assessed: endothelial function measured by flow-mediated dilatation (FMD), carotid femoral by pulse wave velocity (PWV), disease status by International Myositis Assessment & Clinical Studies Group (IMACS) set score, the ventilatory anaerobic threefold (VAT), respiratory compensation point (RCP), maximum effort (ME), maximal oxygen uptake (VO2max) measured by ergospyrometer, and strength and muscle function. Results. Mean age of the patients and duration of disease were 43.9 and 10.5 years, respectively. The median FMD and PWV were 10.2% and 7.1 m/s. After exercise training, important FMD reduction was observed in 4 out of 5 patients, whereas the PWV parameters decreased in only 2 out of 5 patients. The exercise training was safe, without clinical intercurrences or disease relapses. Moreover, an increase in strength and functionality was observed. Concerning aerobic capacity, there was a decrease in the VAT and an increase in ME, without al-terations in the maximum oxygen consumption. Conclusions. In general, exercise training does not alter endothelial function and PWV values, but improves muscle strength and function and also, does not lead to disease reactivation (Clinical Trials (NCT03092167)).

The Efficacy of Banxia Baizhu Tianma Decoction(半夏白术天麻汤)Combined with Xuefu Zhuyu Decoction(血府逐瘀汤)for Essential Hypertension and the Effects on Endothelial Function:A Systematic Review and Meta-analysis

Objective:Banxia Baizhu Tianma Decoction(半夏白术天麻汤,BBTD)combined with Xuefu Zhuyu Decoction(血府逐瘀汤,XFZYD)is widely used to treat essential hypertension in China,but its efficacy remains largely unexplored.We systemically summarized relevant evidence from randomized controlled trials(RCTs)to assess the therapeutic efficacy of BBTD+XFZYD.Methods:This review retrieved 6 databases like Pubmed,Cochrane Library,Embase,CNKI,et al.RCTs of BBTD+XFZYD plus conventional Western drugs(experimental group)and conventional Western drugs alone(control group)for hypertension was collected from the database establishment to August 5,2020.And the outcomes included clinical total effective rate,systolic blood pressure(SBP),diastolic blood pressure(DBP),nitric oxide(NO)and endothelin-1(ET-1).All studies’risk of bias were assessed by the Cochrane Collaboration tool 5.1.0.The data was statistically analyzed by RevMan5.3 Software.Results:Six studies with 608 participants were identified.About duration of treatment,4 studies were 1 month,2 studies were 2 months.The quality presented a high risk of bias.The experimental group showed that clinical total effective rate of the 1-month and 2-month was higher(P<0.00001),the systolic pressure was significantly lower(P<0.05),the NO increased(P<0.00001),and the ET-1 decreased(P<0.00001)compared with the conventional Western drugs used alone.However,DBP was significantly lower(P<0.05)at 2 months of treatment.Conclusion:BBTD+XFZYD plus conventional Western drugs might reduce blood pressure,improve clinical efficacy,repair endothelial function,but still need high-quality RCTs to better assess the outcomes.

Effect of Carvedilol on the Coronary Vascular Endothelial Function after Percutaneous Transluminal Coronary Angioplasty

Objectives To understand the effect of carvedilol on the coronary vascular endothelial function of the patients with coronary heart disease after percutaneous transluminal coronary angioplasty (PTCA). Methods 51cases, having one or more than two branches narrow ( ≥ 70% ) , were diagnosed by coronary angiography. These patients were divided randomly into carvedilol group (n = 28) and control group ( n = 23) who did not take carvedilol. Endothelin (ET) and nitro dioxide (NO) levels of peripheral blood were measured before and after PTCA, before and after two weeks by taking earvedilol. Results Compared with the ET and NO levels before PTCA, ET were markedly increased and NO were decreased after PTCA (p <0. 05) ; compared with the ET and NO levels before taking carvedilol, ET were decreased and NO were increased after two week (p <0.05 ) , but the ET and NO levels of the control group did not change in the period of two weeks observation (p > 0.05). Conclusions Carvedilol may improve the coronary vascular endothelial function after PTCA.

Circadian disturbance induces erectile dysfunction by impairing endothelial function

In order to explore the impact of circadian disturbance on erectile function,we randomly divided 24 adult male rats into groups of control(light on at 8:00 a.m.and off at 8:00 p.m.),dark/dark(DD;constant dark),light/light(LL;constant light),and shift dark/light(DL;light off at 8:00 a.m.and on at 8:0o p.m.).Four weeks later,erectile function was measured and corpora cavernosa were harvested for analysis.The maximum intracavernous pressure(mlcP)and mCP/mean arterial pressure(MAP)ratio in the DD,LL,and DL groups were significantly lower than that in the control group.The LL and DL groups showed significantly attenuated endothelial nitric oxide synthase(eNOS),while DD,LL,and DL showed reduced neuronal nitric oxide synthase(nNOS)at both mRNA and protein levels.The production of nitric oxide(NO)and cyclic guanosinemonophosphate(cGMP)was inhibited by altered light/dark cycles to varying degrees.Circadian disturbance impaired endothelial function and contributed to erectile dysfunction.For the core circadian elements,mRNA expression of circadian locomotor output cycles kaput(Clock)and brain/muscle aryl-hydrocarbon receptor nuclear translocator-like protein 1(Bmal1)was elevated in the DL group,but their protein expression was not significantly changed.DD,LL,and DL increased period 1(Per1)and Per3 levels,while LL and DL increased PER1 levels.No significant difference was found for Per2levels,and PER2 and PER3 concentrations were not significantly changed.Moreover,LL and DL significantly increased cryptochrome-1(CRY1)and CRY2 at both mRNA and protein levels.The altered light/dark rat model showed that circadian disturbance contributed to erectile dysfunction probably by impairing endothelial function.Meanwhile,the core circadian elements were detected in the corpora cavernosa,but these were disrupted.However,which circadian element regulates erectile function and how it works need further analysis.

Differences in vascular endothelial function and serum proteome between obese people with phlegm-dampness constitution and balanced constitution

OBJECTIVE:To evaluate the extent of vascular endothelial dysfunction and preliminary identify serum protein biomarkers associated with obese individuals at risk for cardiovascular disease(CVD).METHODS:Fifteen obese volunteers with the phlegmdampness constitution or balanced constitution were recruited for this study respectively.The clinical baseline data was collected,and the vascular endothelial function was evaluated using the EndoPAT?.Blood samples were collected for the serum proteome analysis.The differences in the serum protein expression levels between the two groups were detected and the protein interaction network analysis,correlation analysis,receiver operating characteristic(ROC)curve analysis,and random forest model investigation were conducted.RESULTS:There were no statistical differences found in the baseline data.For vascular endothelial function,the reactive hyperemia index(RHI)of the phlegm-dampness constitution obese group was significantly lower than that of the balanced constitution obese group(1.46±0.30 vs 2.82±0.78,P<0.0001),indicating vascular endothelial dysfunction.There are 66 differentially expressed serum proteins between the two groups.apolipoprotein A2(Apo A2),angiotensin-converting enzyme 2(ACE-2),interleukin-33(IL-33),and forkhead box P3(FoxP3)showed significant differences and area under curve values of their ROC curves were greater than 0.7 and correlated significantly with RHI.CONCLUSION:Vascular endothelial dysfunction was present in the phlegm-dampness constitution obese group.Thus,alterations in the expression levels of key serum proteins,including Apo A2,ACE-2,IL-33,and Fox P3 could serve as potential biomarkers in the obese population at risk of CVD.

Endothelial METRNL determines circulating METRNL level and maintains endothelial function against atherosclerosis

METRNL is a recently identified secreted protein with emerging functions.This study is to find major cellular source of circulating METRNL and to determine METRNL novel function.Here,we show METRNL is abundant in human and mouse vascular endothelium and released by endothelial cells using endoplasmic reticulum-Golgi apparatus pathway.By creating endothelial cell-specific Metrnl knockout mice,combined with bone marrow transplantation to produce bone marrow-specific deletion of Metrnl,we demonstrate that most of circulating METRNL(approximately 75%)originates from the endothelial cells.Both endothelial and circulating METRNL decrease in atherosclerosis mice and patients.By generating endothelial cell-specific Metrnl knockout in apolipoprotein E-deficient mice,combined with bone marrow-specific deletion of Metrnl in apolipoprotein E-deficient mice,we further demonstrate that endothelial METRNL deficiency accelerates atherosclerosis.Mechanically,endothelial METRNL deficiency causes vascular endothelial dysfunction including vasodilation impairment via reducing eNOS phosphorylation at Ser1177 and inflammation activation via enhancing NFκB pathway,which promotes the susceptibility of atherosclerosis.Exogenous METRNL rescues METRNL deficiency induced endothelial dysfunction.These findings reveal that METRNL is a new endothelial substance not only determining the circulating METRNL level but also regulating endothelial function for vascular health and disease.METRNL is a therapeutic target against endothelial dysfunction and atherosclerosis.

Influence of High Blood Glucose Fluctuation on Endothelial Function of Type 2 Diabetes Mellitus Rats and Effects of Panax Quinquefolius Saponin of Stem and Leaf

Objective： To observe the influence of high blood glucose fluctuation on the endothelial function of type 2 diabetes mellitus （T2DM） rats and the effects of Panax Quinquefolius Saponin （PQS） of stem and leaf. Methods： The T2DM model was induced by intraperitoneal injection of a small dose of streptozotocin （STZ, 35 mg/kg） plus high fat and high caloric laboratory chow. Then, diabetic rats were divided into steady high blood glucose （SHG） group and fluctuant high blood glucose （FHG） group according to fasting blood glucose coefficient of variation （FBG-CV）, and then, the FHG group rats were divided into 4 groups according to the level of FBG-CV and fasting blood glucose： PQS 30 mg/（kg·d） group, PQS 60 mg/（kg·d） group, metformin hydrochloride control （MHC） group, and FHG control group, 10 in each group. Meanwhile, 10 rats without any treatment were used as normal control （NOR） group. Eight weeks later, the aortic arteries histology, plasma hepatocyte growth factor （HGF）, and serum nitric oxide （NO）, endothelin-1 （ET-1）, tumor necrosis factor α （TNF-α）, and soluble intercellular adhesion molecule 1 （slCAM-1） were measured. Results： In comparison with the NOR group, the level of plasma HGF and serum NO, ET-1 and TNF-α, and slCAM-1 in SHG and FHG control groups were all significantly increased （P〈0.01）; in comparison with the SHG group, plasma HGF and serum NO, ET-1, TNF-α, and slCAM-1 in FHG group were all significantly increased further （P〈0.01 or P〈0.05）; meanwhile, in comparison with the FHG control group, the level of plasma HGF and serum NO, ET-1, TNF- α, and slCAM-1 in PQS and MHC groups were all decreased significantly （P〈0.01）. However, comparison of the aortic arteries histology among groups showed no significant differences either before or after treatment. Conclusion： Blood glucose fluctuation could facilitate the development of vascular endothelial dysfunction in T2DM rats, while PQS could improve the endothelial function of T2DM rats with high blood glucose fluctuation, which may be related to its effects of relieving vessel stress, decreasing vasoconstrictor ET-1 production, preventing compensated increase of NO, and reducing inflammatory reaction.

Increased brachial-ankle pulse wave velocity is associated with impaired endothelial function in patients with coronary artery disease

Background Pulse wave velocity and flow-mediated vasodilation （FMD） are widely used as noninvasive modalities for evaluating atherosclerosis. However, it is not known whether pulse wave velocity is related to FMD in patients with coronary artery disease （CAD）. Therefore, the present study was designed to investigate the alteration in brachial-ankle pulse wave velocity （baPWV） and endothelial function in CAD patients. Methods Thirty-three patients with CAD and thirty control subjects were recruited for this study, baPWV was measured non-invasively using a VP 1000 automated PWV/ABI analyzer （PWV/ABI, Colin Co. Ltd., Komaki, Japan）. Endothelial function as reflected by FMD in the brachial artery was assessed with a high-resolution ultrasound device. Results baPWV was increased in CAD patients compared with control subjects [（1756.1±253.1） cm/s vs （1495.3±202.3） cm/s, P〈0.01]. FMD was significantly reduced in CAD patients compared with control subjects [（5.2±2.1） % vs （11.1±4.4） %, P〈0.01]. baPWV correlated with FMD （r =-0.68, P〈0.001）. The endothelium-independent vasodilation induced by sublingual nitroglycerin in the brachial artery was similar in the CAD group compared with the control group.Conclusions CAD is associated with increased baPWV and endothelial dysfunction. Increased baPWV parallels diminished endothelial function. Our data therefore suggest that baPWV can be used as a noninvasive surrogate index in clinical evaluation of endothelial function.

Effect of Ginkgo Leaf Extract on Vascular Endothelial Function in Patients with Early Stage Diabetic Nephropathy

Objective:To explore the effect of ginkgo leaf extract(GLE) on vascular endothelial function(VEF) in patients with early stage diabetic nephropathy(DN).Methods:Sixty-four patients were randomized equally by a randomzing digital table into two groups,the treated group and the control group.They were all treated for 8 weeks with conventional therapy for diabetes,but GLE tablets were given to the treated group additionally. Changes in VEF were estimated before and after treatment by ultrasonic examination of t...

Associations among cerebral microbleeds, cerebral large-artery diseases and endothelial function

Background Endothelial dysfunction is not only an early stage of atherosclerosis,but also involved in the pathogenesis of cerebral small-vessel diseases.Patients with cerebral microbleeds （CMBs） may have arteriolosclerosis as well as systemic atherosclerosis.However,little is known about the associations among CMBs,atherosclerosis of cerebral large arteries,and endothelial function.Our study aimed to investigate the relationships among them.Methods This was a cross-sectional study.Ninety patients hospitalized in Peking University First Hospital with acute ischemic stroke were enrolled consecutively between November 1,2007 and January 31,2008.All subjects underwent transcranial Doppler and carotid color duplex ultrasonography to record the intima-media thickness （IMT） of common carotid artery,carotid plaque,and cerebral artery stenosis.Brain magnetic resonance imaging （MRI） routine sequences and gradient recall-echo T2＊-weighted imaging were performed to count CMBs with clinical data blindness.Endothelial function was evaluated using flow-mediated dilation （FMD） and nitroglycerin-mediated dilation （NMD） of the brachial artery.FMD and NMD were examined by an experienced vascular sonographer using a high-resolution ultrasound.Results Thirty cases （33.3%） had CMBs with counts ranging from 1 to 30.Both FMD （（9.9＆#177;4.8）% vs.（15.2＆#177;7.4）%,P=0.001） and NMD （（13.7＆#177;6.1）% vs.（19.0＆#177;7.4）%,P=0.001） were significantly decreased in CMB-positive patients than in CMB-negative patients.No significant relationships were demonstrated between CMBs and intracranial and/or extracranial artery stenosis.The frequencies of CMBs in patients with IMT≥1.0 mm,carotid plaque,and extracranial artery stenosis were 37.5%,39.4%,and 47.6% respectively,with no significant difference,but much higher than in patients with IMT 〈1.0 mm （5%,P 〈0.05）.In Logistic regression analysis,impaired FMD （OR=5.783,95% CI 1.652-6.718,P=0.007） and high pulse pressure （OR=6.228,95% CI 1.594-3.891,P=0.009） were independently associated with the presence of CMBs,as well as previous ischemic stroke.In contrast,NMD was not correlated with CMBs.Conclusions CMBs may coexist with cerebral atherosclerosis in ischemic stroke.Endothelial dysfunction may play a role in the pathogenesis of CMBs,but may not simply reflect functional alterations of large arteries.