Effects of PEAR1 gene polymorphism on big endothelin-1 levels in Chinese patients with acute myocardial infarction after percutaneous coronary intervention

Acute myocardial infarction (AMI) has been associated with poor prognosis,even after revascularization with percutaneous coronary intervention (PCI),likely due to coronary endothelial cell dysfunction and injury.^([1,2])Endothelin-1 (ET-1),a peptide that serves as a vasoconstrictor of smooth muscle cell proliferation,can reflect endothelial cell functional states.Due to low circulation levels and short plasma half-life time,measuring plasma ET-1 levels is difficult.In contrast,big ET-1.

Corrigendum: Astrocytic endothelin-1 overexpression impairs learning and memory ability in ischemic stroke via altered hippocampal neurogenesis and lipid metabolism

In the article titled“Astrocytic endothelin-1 overexpression impairs learning and memory ability in ischemic stroke via altered hippocampal neurogenesis and lipid metabolism,”published on pages 650-656,Issue 3,Volume 19 of Neural Regeneration Research(Li et al.,2024),there were two errors that needed to be corrected.

Effects of Dezocine and Propofol Combination on Plasma 5-HT and ET Levels in Stroke Patients Undergoing Thrombolysis

Objective: To investigate the effect of dezocine combined with propofol on brain metabolism in patients undergoing cerebral thrombosis thrombolysis. Methods: A total of 86 stroke patients admitted between July 2022 and December 2023 were randomly divided into two groups: Group A (study group) and Group B (control group), with 43 patients in each group. Both groups underwent intra-arterial thrombolysis therapy. Group B received dezocine for anesthesia, while Group A received a combination of dezocine and propofol. Plasma concentrations of 5-hydroxytryptamine and endothelin, as well as brain metabolic indicators, were compared between the two groups immediately after anesthesia, at 1 hour post-reperfusion, and 3 hours post-reperfusion. Results: There were no significant differences in the levels of 5-hydroxytryptamine and endothelin between the two groups immediately after anesthesia and at 1 hour post-reperfusion (P > 0.05). However, at 3 hours post-reperfusion, the levels of 5-hydroxytryptamine and endothelin in Group A were significantly lower than those in Group B. Furthermore, in Group A, the levels of 5-hydroxytryptamine and endothelin at 3 hours post-reperfusion were lower compared to the levels at 1 hour post-reperfusion (P < 0.05). Conclusion: Dezocine combined with propofol can effectively improve the quality of anesthesia and has a minimal effect on brain metabolic indices, suggesting reduced damage to brain metabolism.

Endothelins and liver cirrhosis

Endothelins are a family of 21‐amino acid oligopeptides,called endothelin‐1(ET‐1),endothelin‐2(ET‐2),and endothelin 3(ET‐3).Endothelins act on hepatocytes,liver endothelial cells,and Kupffer cells in a paracrine or autocrine manner through two G protein‐coated receptors,called endothelin A and B receptors,which are mainly located in interlobular veins,interlobular artery endothelial cells and hepatic stellate cells(HSCs).ET B receptor(ETBR)‐1 is responsible for the induction of endothelial nitric oxide synthase,resulting in nitric oxide release and vasodilatation,whereas ETBR‐2 is located on HSCs and is responsible for vasoconstriction.Endothelins are not stored in the organs.Approximately 20%of endothelins are secreted into the circulation system,and are rapidly cleared by the lungs,liver,heart,and kidneys.As a potent vasoconstrictor,endothelins may have a key role for the treatment of hypertensive vascular diseases,inflammation,fibrosis,and metabolic diseases.By clearing ET‐1 from the circulation,endothelin A receptor(ETAR)antagonists can reduce intraportal vascular resistance by dilatating the portal vein,reducing the contraction of HSCs,increasing the diameter of sinusoids,facilitating the regression of liver fibrosis,and restoring liver parenchyma.ET‐1 induces nitric oxide synthase and upregulates cyclooxygenase 2 mRNA levels,making it a key factor during the onset of fibrosis and in the prognosis of patient outcomes.Endothelins can be used to treat porto‐pulmonary hypertension,portal hypertension,angiogenesis,and liver fibrosis and have been approved for the treatment of porto‐pulmonary hypertension.Endothelins are produced on mesangial cells,podocytes,tubular epithelium,and renal collecting tubes in high amounts.Activation of ETAR supports the progression of kidney diseases,whereas activation of ETBR has protective effects on the kidneys.ET‐1 plays an important role in normal cardiovascular homeostasis.Endothelins are closely associated with severe systemic hypertension,congestive heart failure,atherosclerosis,and pulmonary hypertension.Dual ET receptor antagonists reduce blood pressure,but have several side effects,including liver toxicity,acute liver failure,accumulation of salt and water,testicular toxicity,headache,and teratogenicity.Liver enzymes should be checked in all patients who have received ET receptor antagonists,and women of childbearing years should use contraception.

Regulatory mechanisms of retinal ganglion cell death in normal tension glaucoma and potential therapies

Normal tension glaucoma(NTG)is a multifactorial optic neuropathy characterized by normal intraocular pressure,progressive retinal ganglion cell(RGC)death,and glaucomatous visual field loss.Recent studies have described the mechanisms underlying the pathogenesis of NTG.In addition to controlling intraocular pressure,neuroprotection and reduction of RGC degeneration may be beneficial therapies for NTG.In this review,we summarized the main regulatory mechanisms of RGC death in NTG,including autophagy,glutamate neurotoxicity,oxidative stress,neuroinflammation,immunity,and vasoconstriction.Autophagy can be induced by retinal hypoxia and axonal damage.In this process,ischemia can cause mutations of optineurin and activate the nuclear factor-kappa B pathway.Glutamate neurotoxicity is induced by the over-stimulation of N-methyl-D-aspartate membrane receptors by glutamate,which occurs in RGCs and induces progressive glaucomatous optic neuropathy.Oxidative stress also participates in NTG-related glaucomatous optic neuropathy.It impairs the mitochondrial and DNA function of RGCs through the apoptosis signal-regulating kinase-JUN N-terminal kinase pathway.Moreover,it increases inflammation and the immune response of RGCs.Endothelin 1 causes endothelial dysfunction and impairment of ocular blood flow,promoting vasospasm and glaucomatous optic neuropathy,as a result of NTG.In conclusion,we discussed research progress on potential options for the protection of RGCs,including TANK binding kinase 1 inhibitors regulating autophagy,N-methyl-D-aspartate receptor antagonists inhibiting glutamate toxicity,ASK1 inhibitors regulating mitochondrial function,and antioxidants inhibiting oxidative stress.In NTG,RGC death is regulated by a network of mechanisms,while various potential targets protect RGCs.Collectively,these findings provide insight into the pathogenesis of NTG and potential therapeutic strategies.

Plasma endothelin and nitric oxide levels in patients with acute pancreatitis

Objective: To explore the changes of plasma endothelin(ET) and nitric oxide (NO) levels in patients with a-cute pancreatitis.Methods: The level of plasma ET was measured by ra-dioactive-immunoassay, and NO by spectrophotometry.Results: The levels of ET, NO and the ET/NO ratioin patients with severe acute pancreatitis(SAP) within24 hours in hospital were all significantly higher thanthose in other groups of patients [(176±8)pg/ml,(97±11) μmol/L, and 1.83±0.12, P<0.01]. Com-pared to healthy controls(N), the levels of ET and NOin patients without pancreatitis acute abdomen (NAP)and patients with mild acute pancreatitis (MAP) in-creased significantly (P<0.01). After appropriate treat-ment, the levels of ET and NO in the MAP groupwere lower (P<0.01). Compared with those beforetreatment, the levels of ET and NO in the SAP groupon the 3rd and 7th day in hospital dropped signifi-cantly(P<0.01).The ET/NO ratio on the 7th daywas also lower than that on admission (P<0.01).Conclusions: The malfunction of endothelial cells andthe increased ET/NO ratio may be related to the mecha-nism of pancreatic microcirculatory disturbance in pa-tients with SAP; early dynamic determination of theseparameters may help predict the prognosis of SAP.

缩宫素对大鼠心肌缺血再灌注后一氧化氮及内皮素-1的影响

目的探讨缩宫素(OT)对大鼠急性心肌缺血再灌注后一氧化氮(NO)与内皮素-1(ET-1)的影响及可能的机制。方法将大鼠随机分为心肌缺血再灌注组(I/R组)、I/R+OT预处理组(I/R+OT组)、假手术组(SH组)和健康对照组(N组)。采用在体大鼠结扎冠状动脉前降支25min后,松扎再灌注120min形成I/R模型,SH组只穿线不结扎。I/R+OT组在缺血前25min腹腔注射OT 0.03μg/kg,其余3组给予等量生理盐水。再灌注结束后测定血清肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、NO及ET-1;再灌注结束时,采用HE染色进行心肌组织形态学分析。结果光镜下观察,N组与SH组心肌细胞排列整齐,无肌纤维破坏,I/R组心肌纤维排列不规则、断裂,心肌间质水肿,较多粒细胞灶状浸润,I/R+OT组可见心肌细胞排列、间质水肿及粒细胞浸润程度介于N组与SH组。与SH组相比,I/R组和I/R+OT组血清CK-MB、LDH、ET-1升高,NO水平降低,差异均有统计学意义(P均<0.05),而N组的表达差异无统计学意义(P>0.05);与I/R组相比,I/R+OT组血清CK-MB、LDH、ET-1降低,NO水平升高,差异均有统计学意义(P均<0.05)。I/R组和I/R+OT组血清NO与ET-1水平呈负相关(P<0.05)。结论 OT预处理对大鼠I/R有保护作用,其作用机制可能与OT增加血清NO水平、降低ET-1水平有关。

Plasma endothelin in patients with endotoxemia and dynamic comparison between vasoconstrictor and vasodilator in cirrhotic patients

INTRODUCTIONPortal hypertension is a common clinical syndromecharacterized by an abnormal increase in portalblood to the systemic circulation, bypassing theliver. Recent studies have reported that humoralsubstances play an important role in thepathogenesis of portal hypertension, either byincreasing vascular resistance at both theintrahepatic and porto-collateral sites or affectingsplanchnic vasodilation with a concomitant increasein parto-collateral blood flow[1-6]

Effects of Electroacupuncture on the Contents of NO,ET and T-AOC in the Brain Tissues of the Cerebral Hemorrhage Model Rats

In the cerebral hemorrhage model rats established by injection of collagenase and heparin into caudate nucleus, the effects of electroacupuncture (EA) on the contents of nitric oxide (NO) and endothelin (ET),and total anti-oxidation capability (T-AOC) in the brain tissues were investigated. It is found that the content of NO in the Shuigou EA group lowered, ET decreased and the T-AOC raised significantly in both the Fengfu EA group and the Shuigou EA group (all P＜0.05) as compared with the model group,indicating that acupuncture can reduce the contents of ET and NO, and increase the T-AOC in the brain tissues of the rats with cerebral hemorrhage.

壮通饮对大鼠心肌缺血血瘀证内皮素1表达的影响

目的观察壮通饮对心肌缺血血瘀证大鼠血清及心肌组织内皮素1(endothelin-1,ET-1)表达的影响,探讨壮通饮对冠心病心肌缺血的保护作用机制。方法采用左冠状动脉结扎法制作大鼠心肌缺血血瘀证模型,并随机分为空白、假手术组、模型组、壮通饮低(6.8g/kg)、中(13.6g/kg)、高(27.2g/kg)剂量组、阳性对照组7个组,灌胃给药治疗4周后,分别采用酶联免疫吸附法(ELISA)和WB(Western blotting)法检测大鼠血清及心肌组织ET-1的表达。结果血清ELISA结果显示,与空白组、假手术组相比,模型组ET-1的表达明显升高(P<0.05),药物干预后,各组均可使ET-1降低,但中剂量组降低ET-1效果最明显(P<0.05)。WB检测结果显示,模型组ET-1的平均灰度值明显高于空白组、假手术组,药物干预后,各组均可使ET-1平均灰度值降低,但中剂量组降低效果最明显。结论壮通饮能减少心肌缺血血瘀证大鼠ET-1的表达,缓解血管收缩,对大鼠心肌缺血有一定的保护作用。

化痰祛浊通络方对自发性高血压大鼠血压一氧化氮、内皮素1及血管紧张素Ⅱ的影响

目的观察化痰祛浊通络方对自发性高血压大鼠(SHR)血压及一氧化氮(NO)、内皮素1(ET-1)及血管紧张素Ⅱ(AngⅡ)的影响,探讨其降压作用机制。方法将15月龄SHR随机分为空白对照组、化痰祛浊通络方组和吲达帕胺组,每组各9只。空白对照组予0.9%氯化钠注射液(10 m L/kg)、化痰祛浊通络方组予化痰祛浊通络方水煎液(生药10 m L/kg)、吲达帕胺组予吲达帕胺溶液(10 mg/kg),均每日1次灌服,连续6周。所有大鼠每周测量尾动脉压,给药6周腹主动脉抽血测定血清NO、ET-1及AngⅡ含量。结果给药6周后,化痰祛浊通络方组和吲达帕胺组给药后均可降低SHR收缩压(SP)和舒张压(DP),与空白对照组及本组给药前比较差异均有统计学意义(P<0.05);化痰祛浊通络方组及吲达帕胺组ET-1和AngⅡ含量均较本组给药前及空白对照组明显降低,NO含量明显升高,差异均有统计学意义(P<0.05)。结论化痰祛浊通络方能明显降低SHR血压,其机制可能是通过下调ET、AngⅡ含量及上调NO含量来发挥降压作用。

Effects of Xin Mai Tong Capsule on Vasoregulatory Peptides in the Patients of Coronary Heart Disease

In order to inquire into the therapeutic effects of Xin Mai Tong Capsule (心脉通胶囊) on coronary heart disease with myocardial ischemia, 40 patients were randomly divided into two groups (Xin Mai Tong group and the control group). The plasma endothelin (ET) levels in the two groups of patients were markedly higher than that of the healthy people (P<0.001), and the calcitonin gene related peptide (CGRP) was similar to that of the healthy people (P>0.05). After treatment, ET and symptomatic scores in the two groups decreased markedly (P<0.01), and their S-T segments were elevated obviously (P<0.01). But the decrease of ET and symptomatic scores and elevation of S-T segment in Xin Mai Tong group were superior to those of the control group (P<0.05～0.01). The CGRP level in the control group did not vary obviously post-treatment, but it increased markedly (P<0.01) with the addition of Xin Mai Tong Capsule in Xin Mai Tong group.

A Clinical Investigation on Garlicin Injectio for Treatment of Unstable Angina Pectoris and Its Actions on Plasma Endothelin and Blood Sugar Levels

To investigate the therapeutic effects and mechanisms of garlicin for treatment of unstable angina pectoris (UAP), garlicin injectio was intravenously dripped 60 mg/day in 34 cases for 10 days. Nitroglycerine was used in 21 cases of the control group. The results showed that the total effective rates in improving symptoms and electrocardiogram after garlicin treatment were respectively 82% and 62%, and that the plasma endothelin and blood sugar levels were markedly lowered in cases with hyperglycemia.

Endothelin and neonatal capsaicin regulate gastric resistance to injury in BDL rats

AIM: To investigate the relationship between primary afferent neurons, endothelin (ET) and the role of its receptors on ethanol-induced gastric damage in cirrhotic rats. METHODS: Cirrhosis and portal hypertension were induced in rats by bile duct ligation (BDL) while controls had a sham operation. The association between ET and afferent neurons on the gastric mucosa was evaluated by capsaicin treatment in newborn rats, the use of ET agonists or antagonists, gastric ET-1 and -3 mRNA and synthetic capacity. Ethanol-induced damage was assessed using ex vivo gastric chamber experiments.Gastric blood flow was measured by laser-Doppler flow-metry. RESULTS: ET-3 and an ETB receptor antagonist sig- nificantly reduced the extent of ethanol-induced gastric damage in BDL rats. Gastric ET-1 and -3 levels were 30% higher in BDL rats compared to control rats. Cap-saicin treatment restored the gastric resistance and blood flow responses to topical application of ethanol in BDL rats and ET-1 and -3 production to levels observed in controls. CONCLUSION: Our results suggest that the reduced resistance of the gastric mucosa of cirrhotic rats to ethanol-induced injury is a phenomenon modulated by ET through the ET B receptor and by sensory afferent neurons.

CLINICAL RESEARCH OF IMPACTS ON PLASMA ENDOTHELIN AND INTELLIGENCE IN MULTI-INFARCT DEMATIA TREATED WITH CLUSTER PRICKING ON HEAD POINTS

Objective To probe into the impacts on the therapeutic effects and endothelin （ET） in multi-infarct dementia （MID） treated with cluster pricking on head points.Methods 60 cases of MID were randomized into acupuncture group and western medicine group,treated with cluster pricking on head points and huperzien A tablet respectively.Plasma ET lever,HDS,ADL and CNFDS （clinical neurological functional defect scoring） were determined before treatment,and the statistical analysis showed that there were no significant difference （P〉0.05）.Results In 8-week treatment,ET level in both groups were decreased,but it was decreased much more obviously in acupuncture group,indicating significant difference in the statistical comparison （P〈0.05）.The scores of HDS and ADL were all up in acupuncture and western medicine groups,but the significant statistical difference was obtained in the comparison between acupuncture group and western medicine group （P〈0.05）.In acupuncture group,the result of CNFDS was much down comparing with that before the treatment,indicating significant difference （P〈0.05）;but in western medicine group,there was no significant difference in CNFDS before and after treatment （P〉0.05）,suggesting that acupuncture reduces CNFDS of MID patient,neither for western medicine.Conclusion Cluster pricking on head points improves the intelligence of MID patient,reduces ET level and grades up HDS and ADL,moreover,it reduces CNFDS of MID patients and releases the symptoms.

冠状动脉阻抗在冠状动脉微栓塞后不同时间段的变化

目的经导管建立冠状动脉微血管栓塞模型,分析微血管栓塞后不同时间段冠状动脉阻抗参数、冠状动脉血流储备和内皮素-1 (endothelin-1,ET-1)的变化情况。方法12周龄的健康小型家猪15头,通过介入方法制作动物模型,通过多普勒导丝、压力导丝和冠状动脉腔内超声导管在心电同步的情况下采集不同时间段前降支中段的冠状动脉多普勒流速、压力信号和腔内超声图像及数据。其中8头采集到基础状态数据,7头采集到微栓塞后2 h数据,6头采集到6 h数据,6头采集到1周时数据．同时采血测定不同时间段血清ET-1浓度的变化。结果冠状动脉微栓塞后冠状动脉血流储备在微栓塞前及微栓塞后2、6 h和1周时分别为1．77±0．30、1．69±0．07、1．24±0．10及1．58±0．22(其中微栓塞后6 h与微栓塞前相比,P<0．05);基础冠状动脉阻抗在微栓塞前及微栓塞后2、6 h和1周时分别为(2．448±1．891)、(3．229±2．872)、(3．197±3．227)和(3．466±2．683)mm Hg·mL-1·s-1 (1 mm Hg=0．133 kPa);一次谐波冠状动脉阻抗分别为(0．538±0．559)、(1．604±1．727)、(0．834±0．858)和(1．233±1．809)mm Hg·mL-1·s-1;最小冠状动脉阻抗分别为(1．778±1．352)、(2．577±2．276)、(2．710±2．733)和(3．039±2．671) mmHg·mL-1·s-1;一次谐波最小冠状动脉阻抗分别为(0．388±0．395)、(0．947±0．844)、(1．639±1．978)和(0．716±0．624)mm Hg·mL-1·s-1(其中微栓塞后6 h与微栓塞前相比,P<0．05)。冠状动脉阻抗储备分别为1．463±0．235、1．265±0．105、1．160±0．068和1．276±0．266(其中微栓塞后6 h与微栓塞前相比, P<0．05)。对冠状动脉阻抗数据进行校正后发现,冠状动脉阻抗储备和一次谐波冠状动脉阻抗是反映微栓塞后微循环功能变化最敏感的指标。微栓塞前ET-1浓度为(123．0±15．3)ng／L,微栓塞后2 h为(138．5±8．2) ng／L,微栓塞后6 h为(140．9±14．8) ng／L,微栓塞后1周时为(119．0±15．6) ng／L,微栓塞后6 h与微栓塞前相比差异有统计学意义(P<0．05)。结论冠状动脉微栓塞后冠状动脉阻抗随时间逐渐增加,其中冠状动脉阻抗储备变化最为敏感,其次是一次谐波最小冠状动脉阻抗。冠状动脉微栓塞后血清ET-1浓度呈先增加后下降的趋势。

A Clinical and Experimental Study on the Protective Effects of Jiangzhi Tongmai Fang on Endothelial Injury

31 cases of atherosclerosis (AS) were treated with Jiang Zhi Tong Mai Fang ([symbol: see text], formula of JZTMF), and its effect was compared with 30 cases treated with lovastatin in the control group. Clinically, the JZTMF formula showed an effect of regulating blood lipids, and therefore it was antiatherosclerotic. The mechanism is, probably, restoration of the function of endothelial cells (EC) by increasing the synthesis of 6-keto-PGF1 alpha and decreasing the release of endothelin (ET) as evidenced in the experimental study.

Effects of the heparin-coated Wiktor-I stent on recovering the balance of ET-1 and CGRP after intracoronary stent implantation

Objective: To study the effects of heparin-coated stent (Wiktor-I) on recovering the balance between endothelin- 1(ET- 1) and calcitonin gene-related peptide (CGRP) both in the plasma of coronary sinus and peripheral vein after stent implantation. Methods: The patients with coronary artery disease (n=30) were divided into non-coated stent (NCS) group (n=16) and heparin-coated stent (HCS) group (n=14). Circulating ET-1 and CGRP levels were measured by radioimmunoassay (RIA) in the 2 groups at the paired sampling sites, namely the coronary sinus (Cs) and peripheral vein (Pv). The ratio of ET/CGRP was also calculated to reflect the balance of ET and CORP. Results: In NCS group plasma ET-1 concentrations exhibited 2 peaks at 0 mm and 12 h after stent implantation, CORP levels were highly consistent with that of ET-1, and the ratio of ET/CGRP increased markedly at post-PTCA 5 mm, persisting until post-stent 12 h. While in HCS group ET-1 levels and the ratio of ET/CGRP were decreased dramatically compared with that of NCS group at 5 min,10 mm and 12 h post-stent (P＜0.05, P＜0.01 and P＜0.05, respectively＝. There was no remarkable difference of CGRP levels between the 2 groups. Conclusions: Heparin-coated stent can decrease the post-stent circulating ET-1 levels and recover the balance between ET-1 and CGRP.

内皮素与心衰关系的研究进展

0 引言 内皮素(endothelin,ET)是1988年由 Yanagisawa等人首先在培养的猪主动脉内皮细胞分离并提纯的由21个氨基酸组成的环形多肽。ET 具有强大的收缩血管、促进血管平滑肌细胞增殖、升高血压、影响心肌收缩力,促进细胞有丝分裂,调节水钠平衡及影响中枢和外周交感神经活性、激活 RAAS系统等作用。ET

高血压病与内皮素的临床与实验研究

内皮素(Endothelin,ET)是血管内皮细胞合成、释放的,是迄今所知体内最强、持续最久的缩血管活性多肽。大量的文献报告实验性高血压动物血浆ET水平明显增加,ET对血管平滑肌细胞有促增生、肥大效应,推测ET在高血压的发病过程中具有重要作用,但ET在高血压的发病学意义有待确定。本工作对原发性和继发性高血压患者以及大鼠腹主动脉狭窄造成的高血压模型上,观察了血浆ET水平的动态变化,以探讨ET在高血压中的发病学意义。材料和方法一、临床资料和方法: (一)病例选择:1.高血压93例,均系我院住院患者,其中(1)原发性高血压符合WHO诊断标准与分期的63例(男36例,女27例),年龄28～71(50.85)岁。