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Involvement of Angiotensin II Type 1 Receptor and Calcium Channel in Vascular Remodeling and Endothelial Dysfunction in Rats with Pressure Overload

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Current Medical Science 2020年第2期40卷 320-326页

作者： Dong-rui CHEN Hui JIANG- Jing CHEN Cheng-chao RUAN Wei-qing HAN Ping-jin GAO State Key Laboratory of Medical Genomics Shanghai Key Laboratory of HypertensionRiuijin HospitalShanghai Jiao Tong Universitry School of MedicineShanghai 200025China Shanghai Institule of hypertension Shanghai 200025China

Vascular remodeling is an adaptive response to various stimuli,including mechanical forces,inflammatory cy tokines and hormones.In the present study,we investigated the role of angiotensinII type 1 receptor(ATIR)and calcium channel in carotid artery remodeling in response to increased biomechanical forces by using the transverse aortic constriction(TAC)rat model.TAC was induced on ten week-old male Sprague Dawley rats and these models were treated with ATIR blocker olmesartan(1 mg/kg/day)or/and calcium channel blocker(CCB)amlodipine(0.5 mgkgday)for 14 days.After the treatment,the right common carotid artery proximal to the band(RCCA-B)was collected for further assay.Results showed that olmesartan,but not amlodipine,significantly prevented TAC-induced adventitial hyperplasia.Similarly,olmesartan,but not amlodipine,significantly prevented vascular inflammation,as indicated by increased tumor necrosis factor a(TNF-a)and increased p65 phosphorylation,an indicator of nuclear factor K-light-chain-enhancer of activated B cells(NFkB)activation in RCCA-B.In contrast,both olmesartan and amlodipine reversed the decreased expression of endothelial nitric oxidase synthase(eNOS)and improved endothelium-dependent vasodilation,whereas combination of olmesartan and amlodipine showed no further synergistic protective effects.These results suggest that AT1R was involved in vascular remodeling and inflammation in response to pressure overload,whereas ATIR and subsequent calcium channel were involved in endothelial dysfunction.

关键词： transverse aortic constriction angiotensin II type I receptor calcium channel vascular remodcling endothelial dysfunction

Portal hypertensive colopathy is associated with portal hypertension severity in cirrhotic patients

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World Journal of Gastroenterology 2009年第38期15卷 4781-4787页

作者： Antonio Diaz-Sanchez Oscar Nuez-Martinez Cecilia Gonzalez-Asanza Ana Matilla Beatriz Merino Diego Rincon Inmaculada Beceiro Maria Vega Catalina Magdalena Salcedo Rafael Baares Gerardo Clemente Liver unit-CIBEREHD.Hospital General Universitario Gregorio Maraón Madrid 28007Spain Gastroenterology unit Hospital Infanta Leonor Gastroenterology unit Hospital Infanta Sofia Department of Gastroenterology Hospital Universitario Príncipe de Asturias

AIM:To assess the prevalence of portal hypertension (PH) related colorectal lesions in liver transplant candidates, and to evaluate its association with the severity of PH.METHODS: Between October 2004 and December 2005, colonoscopy was performed in 92 cirrhotic liver transplant candidates. We described the lesions resulting from colorectal PH and their association with the grade of PH in 77 patients who underwent measurement of hepatic venous pressure gradient (HVPG).RESULTS: Mean age was 55 years and 80.7% of patients were men. The main etiology of cirrhosis was alcoholism (45.5%). Portal hypertensive colopathy (PHC) was found in 23.9%, colonic varices in 7.6% and polyps in 38% of patients (adenomatous type 65.2%). One asymptomatic patient had a well-differentiated adenocarcinoma. The manifestations of colorectal PH were not associated with the etiology of liver disease or with the Child-Pugh grade. Ninety percent of patients with colopathy presented with gastroesopha-geal varices (GEV), and 27.5% of patients with GEV presented with colopathy (P=0.12). A relationship between higher values of HVPG and presence of col-opathy was observed (19.9±6.2 mmHg vs 16.8±5.4 mmHg, P=0.045), but not with the grade of col-opathy (P=0.13). Preneoplastic polyps and neoplasm (P=0.02) and spontaneous bacterial peritonitis (P=0.006) were more prevalent in patients with colopathy. We did not observe any association between previous β-blocker therapy and the presence of colorectal portal hypertensive vasculopathy.CONCLUSION: PHC is common in cirrhotic liver trans-plant candidates and is associated with higher portal pressure.

关键词：严重程度门静脉肝硬化患者高压结肠压性

Portal hypertension in polycystic liver disease patients does not affect wait-list or immediate post-liver transplantation outcomes

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World Journal of Gastroenterology 2016年第45期22卷 9966-9973页

作者： Neil Rajoriya Dhiraj Tripathi Joanna A Leithead Bridget K Gunson Sophie Lord James W Ferguson Gideon M Hirschfield Liver unit Queen Elizabeth Hospital Centre for Liver Research NIHR Birmingham Liver Biomedical Research Unit University of Birmingham

AIM To establish the impact of portal hypertension(PH) on wait-list/post-transplant outcomes in patients with polycystic liver disease(PCLD) listed for liver transplantation. METHODS A retrospective single-centre case controlled study of consecutive patients listed for liver transplantation over 12 years was performed from our centre. PH in the PCLD cohort was defined by the one or more of following parameters:(1) presence of radiological or endoscopic documented varices from our own centre or the referral centre;(2) splenomegaly(> 11 cm) on radiology inabsence of splenic cysts accounting for increased imaging size;(3) thrombocytopenia(platelets hypertension in patients with PCLD listed for liver transplantation does not appear to have a major impact on wait-list or peri-transplant morbidity.

关键词： Polycystic 肝疾病门高血压肝移植

Refining the Role of Simultaneous Liver Kidney Transplantation

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Journal of Clinical and Translational Hepatology 2018年第3期6卷 289-295页

作者： Sabiha M.Hussain Kalathil K.Sureshkumar Division of Nephrology and hypertension Department of MedicineAllegheny General HospitalAllegheny Health NetworkPittsburghPAUSA

Adoption of the model for end-stage liver disease score by Organ Procurement and Transplant Network(OPTN)deceased donor liver allocation policy in 2002 has led to an increase in the number of simultaneous liver kidney(SLK)transplantation.Since kidney function recovery following liver transplantation is difficult to predict,al ocation of the kidney for SLK trans-plantation thus far has not been based on much rationale and evidence.Lack of OPTN policy towards SLK organ allocation has resulted in great variations among transplant centers regarding SLK transplantation.Increasing use of kidneys towards SLK transplantation diverts deceased donor kidneys away from candidates awaiting kidney-alone transplantation.Recently OPTN/united Network of Organ Sharing has imple-mented medical eligibility criteria for adult SLK transplantation which also includes a concept of safety net.Implementation of the new policy is a move in a positive direction,providing consistency in our practice and evidence-based guidelines in selecting candidates for SLK transplantation.This policy needs to be monitored prospectively and modified based on new data that wil emerge over time.This review outlines the literature on SLK transplantation and efforts towards developing rational policy on SLK organ allocation.

关键词： Liver kidney transplantation Graft survival MELD score Creatinine GFR

PLATELET FREE CALCIUM AND SERUM FREE CALCIUM IN ESSENTIAL hypertension

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Medical Bulletin of Shanghai Jiaotong University 1990年第2期13卷 7-12页

作者：陈实赵光胜李迪元朱鼎良孔德汶 Shanghai Institute of hypertension SSMU Shanghai

Intracellular free calcium of platelets and serum free calcium were studied in human essential hypertension. Intracellular free calcium of platelets was significantly higher in hypertensive patients than that in normotensive subjects, and this was correlated with blood pressure. There was no difference of serum free calcium between hypertensives and normotensive controls. Antihypertensive treatment with nifedipine resulted in a reduction of platelet free calcium, and this was correlated with the fall of blood pressure. In patients treated with clonidine, although there was no difference of platelet free calcium between hypertensives and normotensive controls, serum free clacium was significantly reduced. These results indicated that intracellular free calcium may be regulated by same hormonal or pharmacological factors which determined the height of blood pressure, calcium channel blockers may be more effective in prevention of cardiovascular and cerebrovascular complications caused by platelet hyperfunction in essential hypertension.

关键词： hypertension calcium platelet nifedipine clonidine

Pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension: How can patients be better selected?

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World Journal of Cardiology 2013年第3期5卷 18-21页

作者： Juan C Grignola Enric Domingo Department of Pathophysiology Faculty of Medicine University of the Republic Pulmonary hypertension unit Maciel Hospital Ministry of the Public Health Area of the Heart University Hospital of Vall d' Hebron Department of Physiology University Autonoma of Barcelona Campus de Bellaterra

Chronic thromboembolic pulmonary hypertension (CTEPH) comprises organizing thrombotic obstructions in the pulmonary arteries by nonresolving thromboemboli, formation of fibrosis and remodeling of pulmonary blood vessels. Surgical pulmonary endarterectomy (PEA) is the therapy of choice for patients with surgically accessible CTEPH, which leads to a profound improvement in hemodynamics, functional class and survival. Select- ing the candidates that will benefit from surgery is still a challenging task. Criteria for surgical suitability have been described but the decision-making for or against surgical intervention remains still subjective. The optimal characterization of the reciprocal contribution of large vessel and small vessel disease in the elevation of pulmonary vascular resistance is crucial for the indication and outcome of PEA. Recently, Toshner et al intended to validate the partition resistance into small and large vessels compartments (upstream resistance:Rup) by the occlusion technique in the preoperative assessment of PEA. We discuss the advantages and disadvantages of Rup and compare it with other hemodynamic predictor to evaluate operative risk in CTEPH patients.

关键词： Pulmonary endarterectomy Operability Chronic thromboembolic pulmonary hypertension Pulmonary artery occluded pressure Pulmonary vascular resistance

Plasma levels of Elabela are associated with coronary angiographic severity in patients with acute coronary syndrome

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Journal of Geriatric Cardiology 2020年第11期17卷 674-679页

作者： Sheng-Li DU Xin-Chun YANG Jiu-Chang ZHONG Le-Feng WANG Yi-Fan FAN Heart Center and Beijing Key Laboratory of hypertension Beijing Chaoyang HospitalCapital Medical UniversityBeijingChina

Background Elabela(ELA) was newly discovered as a novel endogenous ligand of the apelin receptor(APJ) which has demonstrated to be crucial for cardiovascular disease such as myocardial infarction, hypertension and heart failure. Previous experiments have revealed that ELA reduced arterial pressure and exerted positive inotropic effects on the heart. However, the role of plasma ELA levels in patients with acute coronary syndrome(ACS) and its relationship with severity of coronary arteries have not been investigated. Methods Two hundred and one subjects who were hospitalized for chest pain and underwent coronary angiography were recruited in this study. One hundred and seventy five patients were diagnosed with ACS and twenty-six subjects with negative coronary angiography were included in the control group. Plasma ELA levels, routine blood test, blood lipid, liver and kidney functions were measured. The number of coronary arteries and SYNTAX(Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score of coronary lesions were used to evaluate the extent of coronary artery stenosis. Results ELA in patients with ACS was significantly higher than that in the control group(P < 0.01). There was no significant difference in plasma ELA levels among patients with single-, double-and triple-vessel diseases. However, in the generalized additive model(GAM), there was a threshold nonlinear correlation between the ELA levels and Syntax I score(P < 0.001). Plasma ELA levels were positively correlated with the Syntax I score when the ELA levels ranged from 63.47 to 85.49 ng/m L. There was no significant association between the plasma ELA levels and the extent of coronary artery stenosis when the ELA levels were less than 63.47 ng/m L or higher than 85.49 ng/m L. Conclusion The present study demonstrates for the first time that plasma ELA levels are increased in patients with ACS. The rise in endogenous ELA levels was associated with severity of coronary stenosis and may be involved in the pathogenesis

关键词： Acute coronary syndrome Coronary artery stenosis Elabela

ACE2/Ang-(1-7) signaling and vascular remodeling

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Science China(Life Sciences) 2014年第8期57卷 802-808页

作者： ZHANG ZhenZhou CHEN LaiJiang ZHONG JiuChang GAO PingJin OUDIT Gavin Y. State Key Laboratory of Medical Genomics Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai Key Laboratory of hypertension Shanghai Institute of Hypertension Department of Medicine University of Alberta Mazankowski Alberta Heart Institute

The renin-angiotensin system(RAS)regulates vascular tone and plays a critical role in vascular remodeling,which is the result of a complex interplay of alterations in vascular tone and structure.Inhibition of the RAS has led to important pharmacological tools to prevent and treat vascular diseases such as hypertension,diabetic vasculopathy and atherosclerosis.Angiotensin converting enzyme 2(ACE2)was recently identified as a multifunctional monocarboxypeptidase responsible for the conversion of angiotensin(Ang)II to Ang-(1-7).The ACE2/Ang-(1-7)signaling has been shown to prevent cellular proliferation,pathological hypertrophy,oxidative stress and vascular fibrosis.Thus,the ACE2/Ang-(1-7)signaling is deemed to be beneficial to the cardiovascular system as a negative regulator of the RAS.The addition of the ACE2/Ang-(1-7)signaling to the complexities of the RAS may lead to the development of novel therapeutics for the treatment of hypertension and other vascular diseases.The present review considers recent findings regarding the ACE2/Ang-(1-7)signaling and focuses on its regulatory roles in processes related to proliferation,inflammation,vascular fibrosis and remodeling,providing proof of principle for the potential use of ACE2 as a novel therapy for vascular disorders related to vascular remodeling.

关键词：血管紧张素转换酶血管重塑信令心血管疾病心血管系统动脉粥样硬化 RAS 治疗学

THE CIRCADIAN ALTERATIONS OF BLOOD PRESSURE IN PATIENTS WITH SECONDARY hypertension

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Journal of Shanghai Second Medical University(Foreign Language Edition) 2001年第1期13卷 56-58页

作者：钱珠王宪衍金翠燕陈丽莎董寿琪 Department of hypertension Ruijin Hospital SSMU

Objective To study the pattern of circadian blood pressure changes in patients with se-condary hypertension. Methods The 24h ambulatory blood pressure monitoring was performed in 80 patients with secondary hypertension (SH) including primary aldosteronism in 44, pheochromocytoma in 11, renovas-cular hypertension in 10, renoparenchymal hypertension in 15 and compared with 80 patients with essential hy-pertension (EH) matched by age and sex. Results The diurnal rhythm in patients with SH was different from that of patients with EU. The diurnal curves in SU and EU was overlapped in daytime and separated from each other at nighttime. The nocturnal blood pressure fall was less and average blood pressure at nighttime was higher in patients with SH than those in patients with Eli (P <0. 01). The nighttime blood pressure loading and non-dipper phenomenon were much more frequently seen in patients with SH than those in patients with Eli (P <0. 01). The nighttime blood pressure/daytime blood pressure ratio was significantly higher in patients with SH than that in patients with Eli (P <0. 01). Conclusion The non-invasive 24h ambulatory blood pressure monitoring may be a useful method in screening for

关键词： ambulatory blood pressure monitoring secondary hypertension essential hypertension