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Circadian disturbance induces erectile dysfunction by impairing endothelial function

Asian Journal of Andrology 2024年第2期26卷 205-211页

作者： Tao Li Yi-Ting Jiang Xin-Zhu Qi Peng Chen Jun-Hao Zhang Fu Luo Jun Qiao Jiang Gu Guang-Shi Du Qiang Wang Department of Urology Affiliated Hospital of Guizhou Medical UniversityGuiyang 550004China Department of Urology Guizhou Provincial People's HospitalGuiyang 550002China Department of Otorhinolaryngology Affiliated Hospital of Guizhou Medical UniversityGuiyang 550004China Guizhou Institute for Food and Drug Control Guiyang 550004China Department of Reproductive Center Guizhou Provincial People's HospitalGuiyang 550002China Translational Medicine Research Center of Guizhou Medical University Guiyang 550025China

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 *** 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 *** on at 8:0o p.m.).Four weeks later,erectile function was measured and corpora cavernosa were harvested for *** 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 *** 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 *** production of nitric oxide(NO)and cyclic guanosinemonophosphate(cGMP)was inhibited by altered light/dark cycles to varying *** disturbance impaired endothelial function and contributed to erectile *** 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 ***,LL,and DL increased period 1(Per1)and Per3 levels,while LL and DL increased PER1 *** significant difference was found for Per2levels,and PER2 and PER3 concentrations were not significantly ***,LL and DL significantly increased cryptochrome-1(CRY1)and CRY2 at both mRNA and protein *** altered light/dark rat model showed that circadian disturbance contributed to erectile dysfunction probably by impairing endothelial ***,the core circadian elements were detected in the corpora cavernosa,but these were ***,which circadian element regulates erectile function and how it works need further analysis.

关键词： circadian disturbance endothelial function erectile function light/dark cycle NO/cGMP

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endothelial function and Carotid Artery Wall Thickening in Patients with Early Essential Hypertension

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Journal of Huazhong University of Science and Technology(Medical Sciences) 1999年第4期19卷 288-290,303页

作者：涂玲魏炜刘晓晴邓又斌余枢 Department of Integration Tongji Hospital Tongji Medical University Wuhan

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 *** 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). 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.

关键词： endothelial function carotid artery hypertension ultrasound

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

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Acta Pharmaceutica Sinica B 2023年第4期13卷 1568-1587页

作者： Sili Zheng Zhiyong Li Jie Song Pin Wang Jian Xu Wenjun Hu Yi Shi Qi Qi Zhuwei Miao Yunfeng Guan Chaoyu Miao Department of Pharmacology Second Military Medical University/Naval Medical UniversityShanghai 200433China Changhai Hospital Second Military Medical University/Naval Medical UniversityShanghai 200433China Zhongshan Hospital Fudan UniversityShanghai 200032China

METRNL is a recently identified secreted protein with emerging *** study is to find major cellular source of circulating METRNL and to determine METRNL novel ***,we show METRNL is abundant in human and mouse vascular endothelium and released by endothelial cells using endoplasmic reticulum-Golgi apparatus *** 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 *** endothelial and circulating METRNL decrease in atherosclerosis mice and *** 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 ***,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 *** METRNL rescues METRNL deficiency induced endothelial *** 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 *** is a therapeutic target against endothelial dysfunction and atherosclerosis.

关键词： METRNL Secreted protein Endothelium endothelial function Bone marrow Atherosclerosis

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Short-term intensive atorvastatin therapy improves endothelial function partly via attenuating perivascular adipose tissue inflammation through 5-lipoxygenase pathway in hyperlipidemic rabbits

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Chinese Medical Journal 2014年第16期127卷 2953-2959页

作者： Wang Xiaoqiao Lin Yongqin Luo Niansang Chen Zhongqing Gu Miaoning Wang Jingfeng Chen Yangxin Department of Anaesthesiology Nanfang Hospital of Southern Medical University Guangzhou Guangdong 510515 China Department of Cardiology Sun Yat-sen Memorial Hospital of SunYat-sen University Guangzhou Guangdong 510120 China Guangdong Province Key Laboratory of Electrophysiology and Arrhythmia Guangzhou Guangdong 510120 China

Background Atherosclerosis is a kind of disease with multiple risk factors,of which hyperlipidemia is a major classical risk factor resulting in its pathogenesis and *** aim of this study was to determine the effects of short-term intensive atorvastatin （IA） therapy on vascular endothelial function and explore the possible mechanisms that may help to explain the clinical benefits from short-term intensive statin *** After exposure to high-fat diet （HFD） for 8 weeks,the animals were,respectively,treated with IA or low-dose atorvastatin （LA） for 5 *** lipids,C-reactive protein （CRP）,tumor necrosis factor-α （TNF-α）,interleukin-6 （IL-6）,nitric oxide （NO）,endothelin-1 （ET-1）,and endothelium-dependent vasorelaxation function were,respectively,*** and protein expression of CRP,TNF-α,IL-6,macrophage chemoattractant protein-1 （MCP-1）,and 5-lipoxygenase （5-LO） were also evaluated in pericarotid adipose tissue （PCAT） and cultured *** HFD increased serum inflammatory factor levels; induced significant hyperlipidemia and endothelial dysfunction,including imbalance between NO and ET-1; enhanced inflammatory factors and 5-LO expression; and promoted macrophage infiltration into adipose ***-day IA therapy could significantly decrease serum inflammatory factor levels and their expression in PCAT; restore the balance between NO and ET-1; and improve endothelial function and macrophage infiltration without significant changes in blood ***,all of the above were not observed in LA *** vitro experiment found that lipopolysaccharide （LPS） enhanced the expression of inflammatory factors and 5-LO in cultured adipocytes,which could be attenuated by short-time （6 hours） treatment of high-dose （5 pmol/L） but not low-dose （0.5 μmol/L） *** addition,inhibiting 5-LO by Cinnamyl-3,4-dihydroxy-α-cyanocinnamate （CDC,a potent and direct 5-LO inhibitor） could significantly downregulate the above-mentioned gene

关键词： atorvastatin endothelial function adipose tissue inflammation 5-lipoxygenase pathway

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

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Chinese Medical Journal 2014年第18期127卷 3204-3208页

作者： Peng Qing Huang Yining Sun Wei Xing Haiying Department of Neurology Peking University First Hospital Beijing 100034 China

Background endothelial dysfunction is not only an early stage of atherosclerosis,but also involved in the pathogenesis of cerebral small-vessel *** with cerebral microbleeds （CMBs） may have arteriolosclerosis as well as systemic ***,little is known about the associations among CMBs,atherosclerosis of cerebral large arteries,and endothelial *** study aimed to investigate the relationships among *** This was a cross-sectional *** patients hospitalized in Peking University First Hospital with acute ischemic stroke were enrolled consecutively between November 1,2007 and January 31,*** 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 *** magnetic resonance imaging （MRI） routine sequences and gradient recall-echo T2＊-weighted imaging were performed to count CMBs with clinical data *** function was evaluated using flow-mediated dilation （FMD） and nitroglycerin-mediated dilation （NMD） of the brachial *** and NMD were examined by an experienced vascular sonographer using a high-resolution *** Thirty cases （33.3%） had CMBs with counts ranging from 1 to *** 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 *** significant relationships were demonstrated between CMBs and intracranial and/or extracranial artery *** 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）

关键词： cerebral small vessel diseases brain ischemia endothelial function magnetic resonance imaging

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

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Asian Journal of Andrology 2008年第2期10卷 214-218页

作者： Lu Fu Qian-Ping Gao Jing-Xia Shen Cardiovascular Department the First Affiliated Hospital of Harbin Medical University Harbin 150001 China

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）

关键词： testosterone coronary heart disease endothelial function

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

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Chinese Medical Journal 2006年第22期119卷 1866-1870页

作者： LIU Dong-hong WANG Yan LIAO Xin-xue XU Ming-guo WANG Jie-mei YANG Zhen CHEN Long LU Ming-de LU Kun TAO Jun Department of Ultrasound First Affiliated Hospital Sun Yat-Sen University Guangzhou 510080 China Department of Cardiology First Affiliated Hospital Sun Yat-Sen University Guangzhou 510080 China

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 *** 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.

关键词： coronary heart disease flow-mediated vasodilation brachial-ankle pulse wave velocity endothelial function

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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

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Chinese Journal of Integrative Medicine 2013年第3期19卷 217-222页

作者：王景尚殷惠军郭春雨黄烨夏城东刘倩 Departmten of Cardiovascular Diseases Xiyuan HospitalChina Academy of Chinese Medical Science

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

关键词： high blood glucose fluctuation endothelial function type 2 diabetes mellitus American ginseng

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

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World Journal of Clinical Cases 2020年第10期8卷 1878-1886页

作者： Jian Zhang Yong-Li Du Hui Zhang Hong Sui Wei-Kai Hou Department of Endocrinology Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina Department of Endocrinology Central Hospital of Tai’an CityTai’an 271000Shandong ProvinceChina Department of Pharmacy Tai'an Central HospitalTai'an 271000Shandong ProvinceChina Department of Rheumatology Tai'an Central HospitalTai'an 271000Shandong ProvinceChina Department of Geriatrics Tai'an Central HospitalTai'an 271000Shandong ProvinceChina

BACKGROUND Diabetes is a clinically common chronic disease,and its incidence has been increasing in recent *** is believed to accelerate the process of atherosclerosis in patients,and abnormal endothelial function is an important factor leading to diabetic kidney *** 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 *** 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 *** The differences in fasting blood glucose,2 h blood glucose,and glycated hemoglobin were not statistically significant between the two groups after *** 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 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.

关键词： Ligliptin Type 2 diabetes Early renal injury Serum endogenous hydrogen sulfide endothelial cell granules endothelial function

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Effect of Ginkgo Leaf Extract on Vascular endothelial function in Patients with Early Stage Diabetic Nephropathy

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Chinese Journal of Integrative Medicine 2009年第1期15卷 26-29页

作者：李旭升郑伟英楼时先陆小文叶赏和 Medical College Jinhua College of Profession and Technology The Affiliated Hospital of Jinhua College of Profession and Technology Medical College Jinhua College of Profession and TechnologyJinhua

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 *** 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...

关键词： ginkgo leaf extract diabetic nephropathy endothelial function von Willebrand factor

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