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AbstractAim:To investigate the association between autoantibodies against angiotensin AT1 receptor (AT1-AAs) and endothelial dysfunction in vivo.Methods:Rat models with AT1 receptor antibodies (AT1-Abs) were established by active immunization for nine months. Lactate dehydrogenase (LDH) activity was regarded as an indicator of cell necrotic death. Endothelin-1 (ET-1) in the sera of rats was determined and endothelium-dependent vasodilatation was detected in isolated thoracic aorta. Endothelial intercellular adhesion molecule-1 (ICAM-1) expression in aorta endothelium was assessed using confocal microscopy. Coronary artery endothelial ultrastructure was observed.Results:IgGs in the immunized group significantly increased the LDH activity (0.84±0.17 vs 0.39±0.12, P<0.01 vs vehicle group IgGs)in incubated human umbilical vein endothelial cells through AT1 receptor. Higher content of ET-1 occurred in the immunized rats than that of the vehicle group, and reached two peaks at month 3 (27±4 ng/L, P<0.01) and month 7 (35±5 ng/L, P<0.01), respectively. In addition, aortic endothelium-dependent vasodilatation was attenuated; endothelial ICAM-1 level was markedly increased and cardiac capillary endothelium was damaged following immunization.Conclusion:Our study demonstrated that AT1-Abs contributed to endothelial dysfunction in vivo, which was a potential mechanism through which the antibodies play vital roles in related diseases. [ABSTRACT FROM AUTHOR]

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Purpose: This study aimed to investigate whether inhibition of glucagon-like peptide-1 (GLP-1) on pressure overload induced cardiac hypertrophy and apoptosis is related to activation of ATP sensitive potassium (KATP) channels. Methods: Male SD rats were randomly divided into five groups: sham, control (abdominal aortic constriction), GLP-1 analog liraglutide (0.3 mg/kg/twice day), KATP channel blocker glibenclamide (5 mg/kg/day), and liraglutide plus glibenclamide. Results: Relative to the control on week 16, liraglutide upregulated protein and mRNA levels of KATP channel subunits Kir6.2/SUR2 and their expression in the myocardium, vascular smooth muscle, aortic endothelium, and cardiac microvasculature. Consistent with a reduction in aortic wall thickness (61.4 ± 7.6 vs. 75.0 ± 7.6 μm, p < 0.05), liraglutide enhanced maximal aortic endothelium-dependent relaxation in response to acetylcholine (71.9 ± 8.7 vs. 38.6 ± 4.8%, p < 0.05). Along with a reduction in heart to body weight ratio (2.6 ± 0.1 vs. 3.4 ± 0.4, mg/g, p < 0.05) by liraglutide, hypertrophied cardiomyocytes (371.0 ± 34.4 vs. 933.6 ± 156.6 μm2, p < 0.05) and apoptotic cells (17.5 ± 8.2 vs. 44.7 ± 7.9%, p < 0.05) were reduced. Expression of anti-apoptotic protein BCL-2 and contents of myocardial ATP were augmented, and expression of cleaved-caspase 3 and levels of serum Tn-I/−T were reduced. Echocardiography and hemodynamic measurement showed that cardiac systolic function was enhanced as evidenced by increased ejection fraction (88.4 ± 4.8 vs. 73.8 ± 5.1%, p < 0.05) and left ventricular systolic pressure (105.2 ± 10.8 vs. 82.7 ± 7.9 mmHg, p < 0.05), and diastolic function was preserved as shown by a reduction of ventricular end-diastolic pressure (−3.1 ± 2.9 vs. 6.7 ± 2.8 mmHg, p < 0.05). Furthermore, left ventricular internal diameter at end-diastole (5.8 ± 0.5 vs. 7.7 ± 0.6 mm, p < 0.05) and left ventricular internal diameter at end-systole (3.0 ± 0.6 vs. 4.7 ± 0.4 mm, p < 0.05) were improved. Dietary administration of glibenclamide alone did not alter all the parameters measured but significantly blocked liraglutide-exerted cardioprotection. Conclusion: Liraglutide ameliorates cardiac hypertrophy and apoptosis, potentially via activating KATP channel-mediated signaling pathway. These data suggest that liraglutide might be considered as an adjuvant therapy to treat patients with heart failure. [ABSTRACT FROM AUTHOR]

Aldosterone produced in adrenal glands by angiotensin II (Ang II) is known to elicit myocardial fibrosis and hypertrophy. This study was designed to test the hypothesis that Ang II causes cardiac morphological changes through the steroidogenic acute regulatory protein (StAR)/aldosterone synthase (AS)-dependent aldosterone synthesis primarily initiated in the heart. Sprague–Dawley rats were randomized to following groups: Ang II infusion for a 4-week period, treatment with telmisartan, spironolactone or adrenalectomy during Ang II infusion. Sham-operated rats served as control. Relative to Sham rats, Ang II infusion significantly increased the protein levels of AT1 receptor, StAR, AS and their tissue expression in the adrenal glands and heart. In coincidence with reduced aldosterone level in the heart, telmisartan, an AT1 receptor blocker, significantly down-regulated the protein level and expression of StAR and AS. Ang II induced changes in the expression of AT1/StAR/AS were not altered by an aldosterone receptor antagonist spironolactone. Furthermore, Ang II augmented migration of macrophages, protein level of TGFβ1, phosphorylation of Smad2/3 and proliferation of myofibroblasts, accompanied by enhanced perivascular/interstitial collagen deposition and cardiomyocyte hypertrophy, which all were significantly abrogated by telmisartan or spironolactone. However, adrenalectomy did not fully suppress Ang II-induced cell migration/proliferation and fibrosis/hypertrophy, indicating a role of aldosterone synthesized within the heart in pathogenesis of Ang II induced injury. These results indicate that myocardial fibrosis and hypertrophy stimulated by Ang II is associated with tissue-specific activation of aldosterone synthesis, primarily mediated by AT1/StAR/AS signaling pathways. [ABSTRACT FROM AUTHOR]

An environmentally friendly biodegradable chelant, [ S, S]-ethylenediaminedisuccinic acid (EDDS), was used to separate heavy metals from sewage sludge based on chemical extraction technology. The extraction of zinc from sewage sludge with an aqueous solution of EDDS was studied under various conditions. It is found that the extraction efficiency of zinc using EDDS is equivalent to that using ethylenediaminetetraacetic acid (EDTA) at the molar ratio of chelant to total heavy metals of 1:1 over pH range of 5-9. EDDS is capable of extracting zinc from the sludge. The extraction efficiency is improved obviously and reaches a higher value within pH range from 3 to 10. The extraction efficiency maintains at about 65% when pH ≥ 4.5 and the ratio of 10:1. By comparing the species contents of the zinc in sewage sludge before and after the extraction, it is found that the extracted zinc mainly comes from the acid soluble, reducible and oxidizable fractions. [ABSTRACT FROM AUTHOR]

The selecting and preparing method of the basic material of magnetic fluid was introduced. By using a chemical method, the magnetic micropowder Fe3O4 was successfully yielded, and an oil-base as a working carrier and dispersing agent was determined. The preparation process of the magnetic fluid and prescription of the oil-base magnetic fluid were discussed. The simulation experimental rig of magnetic fluid sealing for propeller shaft was designed. The sealing ability experiment was conducted and results were analyzed. The pressure of sealing is up to 2 MPa. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to determine whether macrophages migrated from the spleen are associated with angiotensin II-induced cardiac fibrosis and hypertension.Methods: Sprague-Dawley rats were subjected to angiotensin II infusion in vehicle (500 ng/kg/min) for up to four weeks. In splenectomy, the spleen was removed before angiotensin II infusion. In the angiotensin II AT1 receptor blockade, telmisartan was administered by gastric gavage (10 mg/kg/day) during angiotensin II infusion. The heart and aorta were isolated for Western blot analysis and immunohistochemistry.Results: Angiotensin II infusion caused a significant reduction in the number of monocytes in the spleen through the AT1 receptor-activated monocyte chemoattractant protein-1. Comparison of angiotensin II infusion, splenectomy and telmisartan comparatively reduced the recruitment of macrophages into the heart. Associated with this change, transforming growth factor β1 expression and myofibroblast proliferation were inhibited, and Smad2/3 and collagen I/III were downregulated. Furthermore, interstitial/perivascular fibrosis was attenuated. These modifications occurred in coincidence with reduced blood pressure. At week 4, invasion of macrophages and myofibroblasts in the thoracic aorta was attenuated and expression of endothelial nitric oxide synthase was upregulated, along with a reduction in aortic fibrosis.Conclusions: These results suggest that macrophages when recruited into the heart and aorta from the spleen potentially contribute to angiotensin II-induced cardiac fibrosis and hypertension. [ABSTRACT FROM AUTHOR]