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Xu T.-Y.,Shanghai JiaoTong University | Sun J.P.,Chinese University of Hong Kong | Lee A.P.-W.,Chinese University of Hong Kong | Yang X.S.,Chinese University of Hong Kong | And 7 more authors.
International Journal of Cardiology | Year: 2014

Background: Two-dimensional speckle tracking echocardiography (2DSTE) has been used widely in research, but rarely in clinical practice because data acquisition and analysis are time-consuming. By reducing the acquisition and analysis time, 3-dimensional STE may improve clinical impact. We investigated the feasibility of 3DSTE myocardial deformation, with comparison to 2DSTE. Methods: Transthoracic 3DSTE and 2DSTE were performed in 230 adults (138 men, 51 ± 14 years, and 142 hypertension, 10 heart failure and 78 normotensive subjects). The variables of LV deformation were analyzed using EchoPAC software. Results: The 3D LV longitudinal (LS) analysiswas feasible in 84.9% of the study subjects,whichwas lower than the 2D analysis (97.2%). The success rates for circumferential strain (CS) and radial strain (RS) were similar between the 2D and 3D techniques. All magnitude of strains measured by 2DSTE and 3DSTE were significantly correlated. The magnitude of 3D LS and CS was lower, but the 3D RS is higher than that of 2DSTE (-18.5±2.8 vs.-21.2± 3.5; 20.8 ± 4.1 vs. 21.7; and 50.0 ± 11.2 vs. 37.7 ± 12.6, respectively). Strains measured by 3DSTE exhibited stronger correlationwith LV ejection fraction (EF) than that by 2DSTE. In inter- and intra-observer reproducibility for 3D LS, CS, RS and AS were acceptable. The mean time of analysis for LV volume, EF and strains was 116 s by 3DSTE, which was significantly shorter than that by 2DSTE (5 min, P < 0.0001). Conclusions: Three-dimensional STE is feasible and reproducible in the estimation of LV function, requires substantially less time than 2DSTE and is a more feasible technique for LV function assessment in clinical practice. © 2014 Elsevier Ireland Ltd. All rights reserved.


Liu L.,Peking University | Liu J.,Institute of Vascular Medicine | Gao Y.,Peking University | Ng C.F.,Chinese University of Hong Kong | And 3 more authors.
Journal of Hypertension | Year: 2015

Objective: Glucagon-like peptide-1 (GLP-1) exerts its actions via activating GLP-1 receptor (GLP-1R). Our previous study showed a reduced GLP-1R expression in spontaneously hypertensive rat (SHR) renal arteries. The present study investigated the mechanisms underlying GLP- 1R downregulation in hypertension. Methods: Intrarenal arteries of normotensive Wistar-Kyoto rat (WKY) and SHR were suspended in the myograph for force measurement. GLP-1R expression was evaluated by both immunofluorescence and western blotting. Protein kinase Ca (PKCa), PKCb, PKCd, and total PKC levels were assayed by western blotting. Results: Immunofluorescence revealed reduced GLP-1R level in SHR renal arteries compared with WKY renal arteries. GLP-1R agonist exendin-4 induced concentrationdependent relaxations in WKY arteries, which mainly depended on the presence of endothelium. GLP-1R antagonist exendin 9-39 inhibited this relaxation in WKY arteries, whereas the relaxations were significantly less in SHR arteries. Ex-vivo treatment with PKC inhibitor GFX, PKCa and PKCb inhibitor Go 6976, and PKCb inhibitor hispidin but not PKCd inhibitor rottlerin improved the impaired relaxations and restored the diminished GLP-1R expression in SHR arteries. Furthermore, PKCb level was greater in SHR than WKY arteries, with no difference in PKCa, PKCd, or total PKC expressions between two rat strains. Treatment with PKC-activating agent phorbol-12- myristate-13-acetate attenuated exendin-4-induced relaxations and reduced GLP-1R expression in WKY arteries, which were reversed by GFX, Go 6976, or hispidin. More relevantly, immunofluorescence of human renal arteries also showed a reduced GLP-1R level in hypertensive patients. Conclusion: The present results provide novel evidence that the reduced GLP-1R expression in SHR renal arteries is most likely mediated through PKCb upregulation; the latter probably contributes to the impaired GLP-1Rmediated vasorelaxations in hypertension. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Van Veldhuisen D.J.,University of Groningen | Braunschweig F.,Karolinska University Hospital | Conraads V.,University of Antwerp | Ford I.,University of Glasgow | And 8 more authors.
Circulation | Year: 2011

BACKGROUND-: Heart failure is associated with frequent hospitalizations, often resulting from volume overload. Measurement of intrathoracic impedance with an implanted device with an audible patient alert may detect increases in pulmonary fluid retention early. We hypothesized that early intervention could prevent hospitalizations and affect outcome. METHODS AND RESULTS-: We studied 335 patients with chronic heart failure who had undergone implantation of an implantable cardioverter-defibrillator alone (18%) or with cardiac resynchronization therapy (82%). All devices featured a monitoring tool to track changes in intrathoracic impedance (OptiVol) and other diagnostic parameters. Patients were randomized to have information available to physicians and patients as an audible alert in case of preset threshold crossings (access arm) or not (control arm). The primary end point was a composite of all-cause mortality and heart failure hospitalizations. During 14.9±5.4 months, this occurred in 48 patients (29%) in the access arm and in 33 patients (20%) in the control arm (P=0.063; hazard ratio, 1.52; 95% confidence interval, 0.97-2.37). This was due mainly to more heart failure hospitalizations (hazard ratio, 1.79; 95% confidence interval, 1.08-2.95; P=0.022), whereas the number of deaths was comparable (19 versus 15; P=0.54). The number of outpatient visits was higher in the access arm (250 versus 84; P<0.0001), with relatively more signs of heart failure among control patients during outpatient visits. Although the trial was terminated as a result of slow enrollment, a post hoc futility analysis indicated that a positive result would have been unlikely. CONCLUSION-: Use of an implantable diagnostic tool to measure intrathoracic impedance with an audible patient alert did not improve outcome and increased heart failure hospitalizations and outpatient visits in heart failure patients. © 2011 American Heart Association, Inc.


Liu L.,Institute of Vascular Medicine | Liu J.,Institute of Vascular Medicine | Wong W.T.,Institute of Vascular Medicine | Tian X.Y.,Institute of Vascular Medicine | And 12 more authors.
Hypertension | Year: 2012

Sitagliptin, a selective dipeptidyl peptidase 4 inhibitor, inhibits the inactivation and degradation of glucagon like peptide 1 (GLP-1), which is used for the treatment of type 2 diabetes mellitus. However, little is known about the role of GLP-1 in hypertension. This study investigated whether the activation of GLP-1 signaling protects endothelial function in hypertension. Two-week sitagliptin treatment (10 mg/kg per day, oral gavage) improved endothelium-dependent relaxation in renal arteries, restored renal blood flow, and reduced systolic blood pressure in spontaneously hypertensive rats. In vivo sitagliptin treatment elevated GLP-1 and GLP-1 receptor expressions, increased cAMP level, and subsequently activated protein kinase A, liver kinase B1, AMP-activated protein kinase-α and endothelial NO synthase in spontaneously hypertensive rat renal arteries. Inhibition of GLP-1 receptor, adenylyl cyclase, protein kinase A, AMP-activated protein kinase-α, or NO synthase reversed the protective effects of sitagliptin. We also demonstrate that GLP-1 receptor agonist exendin 4 in vitro treatment had similar vasoprotective effects in spontaneously hypertensive rat renal arteries and increased NO production in spontaneously hypertensive rat aortic endothelial cells. Studies using transient expressions of wild-type and dominant-negative AMP-activated protein kinase-α2 support the critical role of AMP-activated protein kinase-α in mediating the effect of GLP-1 in endothelial cells. Ex vivo exendin 4 treatment also improved endothelial function of renal arteries from hypertensive patients. Our results elucidate that upregulation of GLP-1 and related agents improve endothelial function in hypertension by restoring NO bioavailability, suggesting that GLP-1 signaling could be a therapeutic target in hypertension-related vascular events. © 2012 American Heart Association, Inc.


Wong W.T.,Institute of Vascular Medicine | Wong W.T.,Chinese University of Hong Kong | Tian X.Y.,Institute of Vascular Medicine | Tian X.Y.,Chinese University of Hong Kong | And 10 more authors.
Antioxidants and Redox Signaling | Year: 2010

The mechanisms underlying the effect of the renin-angiotensin-aldosterone system (RAAS) inhibition on endothelial dysfunction in type 2 diabetes are incompletely understood. This study explored a causal relationship between RAAS activation and oxidative stress involved in diabetes-associated endothelial dysfunction. Daily oral administration of valsartan or enalapril at 10mg/kg/day to db/db mice for 6 weeks reversed the blunted acetylcholine-induced endothelium-dependent dilatations, suppressed the upregulated expression of angiotensin II type 1 receptor (AT1R) and NAD(P)H oxidase subunits (p22phox and p47phox), and reduced reactive oxygen species (ROS) production. Acute exposure to AT1R blocker losartan restored the impaired endothelium-dependent dilatations in aortas of db/db mice and also in renal arteries of diabetic patients (fasting plasma glucose level ≥7.0 mmol/l). Similar observations were also made with apocynin, diphenyliodonium, or tempol treatment in db/db mouse aortas. DHE fluorescence revealed an overproduction of ROS in db/db aortas which was sensitive to inhibition by losartan or ROS scavengers. Losartan also prevented the impairment of endothelium-dependent dilatations under hyperglycemic conditions that were accompanied by high ROS production. The present study has identified an initiative role of AT1R activation in mediating endothelial dysfunction of arteries from db/db mice and diabetic patients. © 2010 Mary Ann Liebert, Inc.

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