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The Schlager mouse as a model of altered retinal phenotype

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Neural Regeneration Research 2020年第3期15卷 512-518页

作者： Lakshini Y.Herat Aaron L.Magno Márcio G.Kiuchi Kristy L.Jackson Revathy Carnagarin Geoffrey A.Head Markus P.Schlaich Vance B.Matthews Dobney Hypertension Centre School of Biomedical Science-Royal Perth Hospital UnitUniversity of Western AustraliaPerthAustralia Research centre Royal Perth HospitalPerthAustralia Dobney Hypertension Centre School of Medicine-Royal Perth Hospital UnitUniversity of Western AustraliaPerthAustralia Neuropharmacology Laboratory Baker Heart and Diabetes InstituteMelbourneAustralia Department of Cardiology and Department of Nephrology Royal Perth HospitalPerthAustralia

hypertension is a risk factor for a large number of vision-threatening eye disorders.In this study,we investigated for the first time the retinal neural structure of the hypertensive BPH/2J mouse(Schlager mouse)and compared it to its control counterpart,the normotensive BPN/3J strain.The BPH/2J mouse is a selectively inbred mouse strain that develops chronic hypertension due to elevated sympathetic nervous system activity.When compared to the BPN/3J strain,the hypertensive BPH/2J mice showed a complete loss of outer layers of the neural retina at 21 weeks of age,which was indicative of a severe vision-threatening disease potentially caused by hypertension.To elucidate whether the retinal neural phenotype in the BPH/2J strain was attributed to increased BP,we investigated the neural retina of both BPN/3J and BPH/2J mice at 4 weeks of age.Our preliminary results showed for the first time that the BPH/2J strain develops severe retinal neural damage at a young age.Our findings suggest that the retinal phenotype in the BPH/2J mouse is possibly due to elevated blood pressure and may be contributed by an early onset spontaneous mutation which is yet to be identified or a congenital defect occurring in this strain.Further characterization of the BPH/2J mouse strain is likely to i)elucidate gene defects underlying retinal disease;ii)understand mechanisms leading to neural retinal disease and iii)permit testing of molecules for translational research to interfere with the progression of retinal disease.The animal experiments were performed with the approval of the Royal Perth Hospital Animal Ethics Committee(R535/17-18)on June 1,2017.

关键词： blood pressure eye hypertension mice neural regeneration retina Schlager mouse sympathetic nervous system

Sodium glucose co-transporter 2 inhibition reduces succinate levels in diabetic mice

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World Journal of Gastroenterology 2020年第23期26卷 3225-3235页

作者： Lakshini Y Herat Natalie C Ward Aaron L Magno Elizabeth P Rakoczy Marcio G Kiuchi Markus P Schlaich Vance B Matthews School of Biomedical Sciences Dobney Hypertension CentreRoyal Perth Hospital UnitUniversity of Western AustraliaPerth 6000Australia Faculty of Health and Medical Sciences University of Western AustraliaCrawley 6009Australia Faculty of Health Sciences School of Public HealthCurtin UniversityBentley 6102Australia Research centre Royal Perth HospitalPerth 6000Australia Department of Molecular Ophthalmology University of Western AustraliaCrawley 6009Australia Dobney Hypertension Centre School of MedicineRoyal Perth Hospital UnitUniversity of Western AustraliaPerth 6000Australia Department of Cardiology and Department of Nephrology Royal Perth HospitalPerth 6000Australia

BACKGROUND Type 1 diabetes(T1D) is associated with major chronic microvascular complications which contribute significantly to diabetes associated morbidity.The protein primarily responsible for glucose reabsorption in the kidney is sodium glucose co-transporter 2(SGLT2). Presently, SGLT2 inhibitors are widely used in diabetic patients to improve blood glucose levels and prevent cardiovascular and renal complications. Given the broad therapeutic application of SGLT2 inhibitors, we hypothesised that SGLT2 inhibition may exert its protective effects via alterations of the gut microbiome and tested this in a type 1 diabetic mouse model of diabetic retinopathy.AIM To determine whether the treatment with two independent SGLT2 inhibitors affects gut health in a type 1 diabetic mouse model.METHODS The SGLT2 inhibitors empagliflozin or dapagliflozin(25 mg/kg/d) or vehicle dimethylsulfoxide(DMSO) were administered to C57 BL/6 J, Akita, Kimba and Akimba mice at 10 wk of age for 8 wk via their drinking water. Serum samples were collected and the concentration of succinate and the short chain fatty acid(SCFA) butyric acid was measured using gas chromatography-mass spectrometry. Enzyme-linked immunosorbent assay(ELISA) was performed to determine the concentration of insulin and leptin. Furthermore, the norepinephrine content in kidney tissue was determined using ELISA. Pancreatic tissue was collected and stained with haematoxylin and eosin and analysed using brightfield microscopy.RESULTS Due to the presence of the Akita allele, both Akita and Akimba mice showed a reduction in insulin production compared to C57 BL/6 J and Kimba mice.Furthermore, Akita mice also showed the presence of apoptotic bodies within the pancreatic islets. The acinar cells of Akita and Akimba mice showed swelling which is indicative of acute injury or pancreatitis. After 8 wk of SGLT2 inhibition with dapagliflozin, the intermediate metabolite of gut metabolism known as succinate was significantly reduced in Akimba mice when compared to DMSO treated mic

关键词： Sodium glucose co-transporter inhibitors Sodium glucose co-transporter 2 Diabetes Diabetic retinopathy Mouse Gut microbiota Empagliflozin Dapagliflozin Succinate Akimba

Ambulatory blood pressure monitoring for the management of hypertension

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Chinese Medical Journal 2022年第9期135卷 1027-1035页

作者： Yibang Cheng Yan Li Jiguang Wang Department of Cardiovascular Medicine Centre for Epidemiological Studies and Clinical TrialsShanghai Key Laboratory of HypertensionThe Shanghai Institute of HypertensionState Key Laboratory of Medical GenomicsNational Research Centre for Translational MedicineDepartment of HypertensionRuijin HospitalShanghai Jiaotong University School of MedicineShanghai 200025China

Ambulatory blood pressure monitoring(ABPM)has become indispensable in the current management of hypertension.ABPM is particularly useful in the accurate diagnosis of hypertension.Its diagnostic thresholds had been recently established based on hard clinical outcomes.Cross-classification of patients according to office and ambulatory blood pressure identifies white-coat,masked,and sustained hypertension.ABPM is also useful in cardiovascular(CV)risk assessment.It provides information on daytime and nighttime blood pressure and circadian rhythm,particularly nighttime blood pressure dipping.Nighttime blood pressure is predictive of CV risk independent of office and daytime blood pressure.Isolated nocturnal hypertension is a special form of masked hypertension,with normal daytime but elevated nocturnal blood pressure.It also helps in the evaluation of blood pressure fluctuation and variation,such as morning blood pressure surge and reading-to-reading blood pressure variability.ABPM may derive several other indexes,such as ambulatory blood pressure index and salt sensitivity index,which may be useful in CV evaluations.

关键词： Ambulatory blood pressure monitoring Blood pressure control hypertension Antihypertensive treatment

Why is the Chinese hypertension guideline necessary?

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Journal of Geriatric Cardiology 2019年第3期16卷 173-175,I0001-I0005页

作者： Ji-Guang WANG centre for Epidemiological Studies and Clinical Trials Shanghai Key Laboratory of Hypertension the Shanghai Institute of Hypertension Department of Hypertension Ruijin Hospital Shanghai Jiaotong University School of Medicine Department of hypertension Ruijin Hospital North Shanghai Jiaotong University School of Medicine Shanghai Jiaotong University School of Public Health

The new Chinese hypertension guideline was eventually published.[1] It has been more than seven years since the previous Chinese hypertension guideline was published in 2011.[2] The guideline committee should also be congratulated that this new Chinese hypertension guideline was for the first time published in full length in the English language in this issue of the Journal of Geriatric Cardiology.[3] This is the fourth Chinese hypertension guideline,[3] after the first,second[4] and third[2] in 1999,2005 and 2011,respectively.The first Chinese hypertension guideline was printed in a booklet.The document was not so sophisticated,but nevertheless played a role in improving management of hypertension at that time in China.The treatment rate of hypertension increased substantially from 45.5% in 1991[5] to 81.8% in 2002[6] in patients who were aware of the disease (Table 1).

关键词： Chinese Guideline hypertension

Predictors of heart rhythm disturbances in hypertensive obese patients with obstructive sleep apnea

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Journal of Geriatric Cardiology 2017年第9期14卷 553-562页

作者： Lyudmila Sergeevna Korostovtseva Nadezhda Edvinovna Zvartau Oxana Petrovna Rotar Yurii Vladimirovich Sviryaev Aleksandra Olegovna Konradi Research Department for hypertension Almazov National Medical Research Centre St Petersburg Russia Institute of TranslationalMedicine ITMO University St Petersburg Russia

Objective To assess the incidence and predictors of heart rhythm and conduction disturbances in hypertensive obese patients with andwithout obstructive sleep apnea （OSA）. Methods This is an open, cohort, prospective study. Out of 493 screened patients, we selected 279hypertensive, obese individuals without severe concomitant diseases： 75 patients without sleep-disordered breathing （non-SDB group）, and204 patients with OSA （OSA group）. At baseline, all patients underwent examination, including ECG, Holter ECG monitoring, and sleepstudy. During follow-up （on 3, 5, 7 and 10th years; phone calls once per 6 months）, information about new events, changes in therapy and lifestyle was collected, diagnostic procedures were performed. As the endpoints, we registered significant heart rhythm and conduction disordersas following： atrial fibrillation （AF）, ventricular tachycardia, atrioventricular block （AV） 2-3 degree, sinoatrial block, significant sinus pauses（〉 2000 ms）, and the required pacemaker implantation. Results The median follow-up was 108 （67.5-120） months. The frequency of heartrhythm disorders was higher in OSA patients （29 cases, X^2= 5.5; P = 0.019） compared to the non-SDB patients （three cases; OR： 3.92, 95%CI： 1.16-13.29）. AF was registered in 15 patients （n = 12 in OSA group; P = 0.77）. Heart conduction disturbance developed in 16 patients,without an association with the rate of coronary artery disease onset. Regression analysis showed that only hypertension duration was anindependent predictor olAF （OR： 1.10, 95% CI： 1.04-1.16; P = 0.001）. In case of heart conduction disturbances, apnea duration was thestrongest predictor （P = 0.002）. Conclusions Hypertensive obese patients with OSA demonstrate 4-fold higher incidence of heart rhythmand conduction disturbances than subjects without SDB. hypertension duration is an independent predictor for AF development, while sleepapneaJhypopnea duration is the main factor for heart conduction disorders onset in hypertensive obese patients with OSA.

关键词： Atrial fibrillation Cardiovascular morbidity Cardiovascular prognosis Heart conduction disorder Obstructive sleep apnea

Outcome Trials in the Therapeutic Management of hypertension in East Asians

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Cardiovascular Innovations and Applications 2016年第B09期1卷 451-459页

作者： Ji-Guang Wang Yan Li centre for Epidemiological Studies and Clinical Trials Shanghai Key Laboratory of HypertensionThe Shanghai Institute of HypertensionDepartment of HypertensionRuijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina

According to the most recent epidemiological data,the prevalence of hypertension ranged from about 25% in Chinese living either in the mainland or in Taiwan and Koreans,to approximately 40% in Mongolians.The control rate of hypertension was about 35% in Koreans and Japanese,24% in Mongolians,and less than 10%in Chinese.Four placebo-controlled trials in China unequivocally proved that antihypertensive therapy may prevent stroke and other cardiovascular complications in hypertension or patients with a history of stroke or transient ischemic attack.Four actively-controlled trials in Japan did not show signifi cant difference between various classes or combinations of antihypertensive drugs.Two trials that compared intensive with less intensive blood pressure control in elderly Japanese hypertensive patients did not show further benefi t of controlling systolic blood pressure to a level below 140 mmHg in comparison with blood pressure control to a level of 140 mmHg or above.These trials that compared various classes of antihypertensive drugs or intensive with less intensive blood pressure control often had small sample size and hence inadequate power to detect modest or moderate benefi t.There is still a need for high quality outcome trial data in East Asians.

关键词： hypertension epidemiology outcome trials East Asian

Unusual circadian hypertension associated with polydipsia

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Journal of Geriatric Cardiology 2016年第11期13卷 932-934页

作者： Jurgen M Bohlender Jurg Nussberger Department of Nephrology Hypertension and Clinical Pharmacology Inselspital Bern University Hospital Freiburgstr. 4 Bern Switzerland Department of Medicine Division of Angiology and Hypertension Centre Hospitalier Universitaire Vaudois (CHUV) Rue du Bugnon 46 Lausanne Switzerland

Healthy people are usually capable of handling a large variability of water and sodium intake efficiently by adjusting urinary volume up to 50-fold and osmolality up to 35-fold without notable changes of blood pressur... 详细信息

关键词：高血压昼夜渗透压尿量

Metabolic syndrome in hypertensive patients:An unholy alliance

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World Journal of Cardiology 2014年第9期6卷 890-907页

作者： Giuseppe Mulè IIenia Calcaterra Emilio Nardi Giovanni Cerasola Santina Cottone Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS) Unit of Nephrology and HypertensionEuropean Society of Hypertension Excellence CentreUniversità di Palermo

For many years, it has been recognized that hypertension tends to cluster with various anthropometric and metabolic abnormalities including abdominal obesity, elevated triglycerides, reduced high-density lipoprotein cholesterol, glucose intolerance, insulin resistance and hyperuricemia. This constellation of various conditions has been transformed from a pathophysiological concept to a clinical entity, which has been defined metabolic syndrome(MetS). The consequences of the MetS have been difficult to assess without commonly accepted criteria to diagnose it. For this reason, on 2009 the International Diabetes Federation, the American Heart Association and other scientific organizations proposed a unified MetS definition. The incidence of the MetS has been increasing worldwide in parallel with an increase in overweight and obesity. The epidemic proportion reached by the MetS represents a major public health challenge, because several lines of evidence showed that the MetS, even without type 2 diabetes, confers an increased risk of cardiovascular morbidity and mortality in different populations including also hypertensive patients. It is likely that the enhanced cardiovascular risk associated with MetS in patients with high blood pressure may be largely mediated through an increased prevalence of preclinical cardiovascular and renal changes, such as left ventricular hypertrophy, early carotid atherosclerosis, impaired aortic elasticity, hypertensive retinopathy and microalbuminuria. Indeed, many reports support this notion, showing that hypertensive patients with MetS exhibit, more often than those without it, these early signs of end organ damage, most of which are recognized as significant independent predictors of adverse cardiovascular outcomes.

关键词： hypertensive cardiovascular hypertrophy obesity intolerance consequences carotid cholesterol prevalence impaired

Rationale and Design of a Randomized Controlled Trial on Intensive Management of Blood PRESSure and Cholesterol in Elderly Chinese with hypertension and Atrial FibrillatION (IMPRESSION)

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Cardiology Discovery 2021年第3期1卷 173-178页

作者： Wei Zhang Yi Chen Qifang Huang Ji-Guang Wang Department of Cardiovascular Medicine Centre for Epidemiological Studies and Clinical TrialsShanghai Key Laboratory of HypertensionThe Shanghai Institute of HypertensionDepartment of HypertensionRuijin HospitalShanghai Jiaotong University School of MedicineShanghai 200025China

hypertension significantly increases the risk of embolic stroke and systemic embolism in patients with atrial fibrillation, while statin therapy can improve long-term outcomes in hypertensive patients at high risk. However, it is still unclear whether patients with both hypertension and atrial fibrillation can benefit from intensive management of blood pressure and cholesterol. IMPRESSION is a 3-year prospective, randomized, open-label, blinded-endpoint investigation. A total of 1200 hypertensive patients with atrial fibrillation from about 40 clinical centers nationwide will be included upon confirming the presence of both hypertension and atrial fibrillation and will be randomly assigned to groups for intensive or standard management of blood pressure and cholesterol. Patients in all groups will have office and home blood pressure measured by the end of the first month and every 3 months thereafter. The effects of blood pressure and cholesterol management strategies in patients with hypertension and atrial fibrillation on fatal and non-fatal stroke, acute myocardial infarction, and cardiovascular death at 3 years will be assessed. The IMPRESSION study protocol has received approval from the Ethics Committee of Ruijin Hospital, Shanghai Jiaotong University School of Medicine. The procedures set out in this protocol are in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice guidelines. The results will be published following the CONSORT statement in a peer-reviewed scientific journal (Trial registration number: NCT04111419).

关键词： Atrial fibrillation Blood pressure hypertension