Publications
100 results found
Li Y-Y, Zhai Z-G, Yang Y-H, et al., 2011, Association of the 894 G > T polymorphism in the endothelial nitric oxide synthase gene with risk of venous thromboembolism in Chinese population, THROMBOSIS RESEARCH, Vol: 127, Pages: 324-327, ISSN: 0049-3848
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- Citations: 13
Robbins IM, Hemnes AR, Gibbs JS, et al., 2011, Safety of sapropterin dihydrochloride (6r-bh4) in patients with pulmonary hypertension, EXPERIMENTAL LUNG RESEARCH, Vol: 37, Pages: 26-34, ISSN: 0190-2148
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- Citations: 32
Zhao L, Zhai Z, Wharton J, et al., 2011, Phosphodiesterase inhibitors in the treatment of pulmonary hypertension, Textbook of pulmonary vascular disease, Editors: Yuan, Garcia, Hales, Rich, Archer, West, Publisher: Springer, Pages: 1477-1486
Chen C, Hajji N, Wilkins M, et al., 2011, Histone Deacetylase Inhibitor, Valproic Acid, Prevents Chronic Hypoxia-Induced Pulmonary Arterial Hypertension, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Zhao L, 2010, Chronic hypoxia-induced pulmonary hypertension in rat: The best animal model for studying pulmonary vasoconstriction and vascular medial hypertrophy, Drug Discovery Today: Disease Models, Vol: 7, Pages: 83-88, ISSN: 1740-6757
Numerous animal models of pulmonary hypertension (PH) are currently used to evaluate new therapies; investigating both their efficacy and the mechanism of their effect. They are also used to explore the biochemical mechanisms at work, with a view of identifying new drug targets. The chronic hypoxia-induced PH rat model is among the most commonly used animal models of PH. It is well known that alveolar hypoxia causes constriction of resistance vessels in the pulmonary vascular bed and followed by medial hypertrophy and muscularization of pulmonary arterioles, leading to sustained elevation in pulmonary artery pressure (PAP). The combination of these physiologic and pathologic processes imposes a mechanical and obliterative impact on the pulmonary circulation which mimics the common clinical features of pulmonary arterial hypertension (PAH) in patients. Researchers have slowly unraveled various etiology components in initiating and modifying influences in the hypoxia-induced PH rat model and the accumulation of knowledge could improve future treatments of PAH. This review examines the strengths and limitations of the chronic hypoxia-induced rat PH model and its value in the assessment of new treatments for PH. © 2011 Elsevier Ltd. All rights reserved.
Francis BN, Wilkins MR, Zhao L, 2010, Tetrahydrobiopterin and the regulation of hypoxic pulmonary vasoconstriction, EUROPEAN RESPIRATORY JOURNAL, Vol: 36, Pages: 323-330, ISSN: 0903-1936
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- Citations: 17
Zhai Z, Wang J, Zhao L, et al., 2010, Pulmonary Hypertension in China Pulmonary Vascular Disease: The Global Perspective, CHEST, Vol: 137, Pages: 69S-77S, ISSN: 0012-3692
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- Citations: 12
Harrington LS, Moreno L, Reed A, et al., 2010, The PPARβ/δAgonist GW0742 Relaxes Pulmonary Vessels and Limits Right Heart Hypertrophy in Rats with Hypoxia-Induced Pulmonary Hypertension, PLOS ONE, Vol: 5, ISSN: 1932-6203
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- Citations: 40
Wang C, Zhai ZG, Shen YH, et al., 2010, Clinical and genetic risk factors for venous thromboembolism in Chinese population, Frontiers of Medicine in China, Vol: 4, Pages: 29-35, ISSN: 1673-7342
Venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, carries significant mortality and morbidity. The most important and effective way to reduce VTE incidence is to identify the patients at risk and give necessary prevention. VTE is a multifactorial and complicated disorder. Major risk factors for VTE include surgery and trauma, acute medical illness, active cancer and pregnancy. Genetic factors increase susceptibility to the disease and are useful in predicting the development of VTE. Gene-gene and gene-environment interactions alter and magnify the clinical picture in this disorder. This brief review summarizes some selected clinical and genetic risk factors for VTE based on the current research in China. © 2010 Higher Education Press and Springer Berlin Heidelberg.
Wilkins MR, Wharton J, Zhao L, 2010, What Animal Models Tell Us about Treatments for Pulmonary Hypertension, 10th Solvay Pharmaceuticals Conference on Pulmonary Arterial Hypertension (PAH), Publisher: IOS PRESS, Pages: 57-69, ISSN: 1566-7685
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- Citations: 2
Wilkins MR, Wharton J, Zhao L, 2010, What animal models tell us about treatments of pulmonary hypertension, Pulmonary arterial hypertension, Editors: Antel, Hesselink, Schermuly, Pages: 57-69
Wang C, JF L, Zhao L, et al., 2009, Inhibition of SOC/Ca2+/NFAT pathway is involved in the anti-proliferative effect of sildenafil on pulmonary artery smooth muscle cells, Respiratory Research, Vol: 10, Pages: 1-7, ISSN: 1465-9921
BackgroundSildenafil, a potent phosphodiesterase type 5 (PDE5) inhibitor, has been proposed as a treatment for pulmonary arterial hypertension (PAH). The mechanism of its anti-proliferative effect on pulmonary artery smooth muscle cells (PASMC) is unclear. Nuclear translocation of nuclear factor of activated T-cells (NFAT) is thought to be involved in PASMC proliferation and PAH. Increase in cytosolic free [Ca2+] ([Ca2+]i) is a prerequisite for NFAT nuclear translocation. Elevated [Ca2+]i in PASMC of PAH patients has been demonstrated through up-regulation of store-operated Ca2+ channels (SOC) which is encoded by the transient receptor potential (TRP) channel protein. Thus we investigated if: 1) up-regulation of TRPC1 channel expression which induces enhancement of SOC-mediated Ca2+ influx and increase in [Ca2+]i is involved in hypoxia-induced PASMC proliferation; 2) hypoxia-induced promotion of [Ca2+]i leads to nuclear translocation of NFAT and regulates PASMC proliferation and TRPC1 expression; 3) the anti-proliferative effect of sildenafil is mediated by inhibition of this SOC/Ca2+/NFAT pathway.MethodsHuman PASMC were cultured under hypoxia (3% O2) with or without sildenafil treatment for 72 h. Cell number and cell viability were determined with a hemocytometer and MTT assay respectively. [Ca2+]i was measured with a dynamic digital Ca2+ imaging system by loading PASMC with fura 2-AM. TRPC1 mRNA and protein level were detected by RT-PCR and Western blotting respectively. Nuclear translocation of NFAT was determined by immunofluoresence microscopy.ResultsHypoxia induced PASMC proliferation with increases in basal [Ca2+]i and Ca2+ entry via SOC (SOCE). These were accompanied by up-regulation of TRPC1 gene and protein expression in PASMC. NFAT nuclear translocation was significantly enhanced by hypoxia, which was dependent on SOCE and sensitive to SOC inhibitor SKF96365 (SKF), as well as cGMP analogue, 8-brom-cGMP. Hypoxia-induced PASMC proliferation and TRPC1 up-reg
Zhao L, Sebkhi A, Ali O, et al., 2009, Simvastatin and sildenafil combine to attenuate pulmonary hypertension, EUROPEAN RESPIRATORY JOURNAL, Vol: 34, Pages: 948-957, ISSN: 0903-1936
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- Citations: 43
Wilkins MR, Zhao L, 2009, [Future treatment of pulmonary arterial hypertension]., Zhonghua Yi Xue Za Zhi, Vol: 89, Pages: 2097-2098, ISSN: 0376-2491
Wilkins MR, Zhao L, 2009, Future treatment of pulmonary arterial hypertension, Zhonghua yi xue za zhi, Vol: 89, Pages: 2097-2098, ISSN: 0376-2491
Wojciak-Stothard B, Torondel B, Zhao L, et al., 2009, Modulation of Rac1 Activity by ADMA/DDAH Regulates Pulmonary Endothelial Barrier Function, MOLECULAR BIOLOGY OF THE CELL, Vol: 20, Pages: 33-42, ISSN: 1059-1524
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- Citations: 49
Baliga RS, Zhao L, Madhani M, et al., 2008, Synergy between natriuretic peptides and phosphodiesterase 5 inhibitors ameliorates pulmonary arterial hypertension, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 178, Pages: 861-869, ISSN: 1073-449X
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- Citations: 48
Wang C, Wang J, Zhao L, et al., 2008, Sildenafil inhibits human pulmonary artery smooth muscle cell proliferation by decreasing capacitative Ca<SUP>2+</SUP> entry, JOURNAL OF PHARMACOLOGICAL SCIENCES, Vol: 108, Pages: 71-78, ISSN: 1347-8613
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- Citations: 40
Zhao L, Bahaa F, Wilkins M, 2007, Tetrarydrobiopterin and pulmonary hypertension, PROBLEMS OF HIGH ALTITUDE MEDICINE AND BIOLOGY, Pages: 69-+, ISSN: 1874-6489
Khoo JP, Zhao L, Alp NJ, et al., 2005, Pivotal role for endothelial tetrahydrobiopterin in pulmonary hypertension, CIRCULATION, Vol: 111, Pages: 2126-2133, ISSN: 0009-7322
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- Citations: 122
Zhao L, Mason NA, Strange JW, et al., 2003, Beneficial effects of phosphodiesterase 5 inhibition in pulmonary hypertension are influenced by natriuretic peptide activity, CIRCULATION, Vol: 107, Pages: 234-237, ISSN: 0009-7322
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- Citations: 80
Zhao L, Mason NA, Morrell NW, et al., 2001, Sildenafil inhibits hypoxia-induced pulmonary hypertension, CIRCULATION, Vol: 104, Pages: 424-428, ISSN: 0009-7322
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- Citations: 367
Zhao L, Sebkhi A, Nunez DJR, et al., 2001, Right ventricular hypertrophy secondary to pulmonary hypertension is linked to rat chromosome 17 - Evaluation of cardiac ryanodine Ryr2 receptor as a candidate, CIRCULATION, Vol: 103, Pages: 442-447, ISSN: 0009-7322
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- Citations: 23
Sebkhi A, Zhao L, Lu L, et al., 1999, Genetic determination of cardiac mass in normotensive rats - Results from an F344 x WKY cross, HYPERTENSION, Vol: 33, Pages: 949-953, ISSN: 0194-911X
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- Citations: 32
Zhao L, Long L, Morrell NW, et al., 1999, NPR-A-deficient mice show increased susceptibility to hypoxia-induced pulmonary hypertension, CIRCULATION, Vol: 99, Pages: 605-607, ISSN: 0009-7322
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- Citations: 73
Li L, He J, Zhao L, 1998, [Epidemiologic features of viral hepatitis in Fujian]., Zhonghua Liu Xing Bing Xue Za Zhi, Vol: 19, Pages: 89-92, ISSN: 0254-6450
To study the prevalence and the epidemiologic features of viral hepatitis in Fujian, a seroepidemiological survey on five kinds of viral hepatitis infection has been carried out in Fujian province since 1992. Using stratified mulitistage random cluster sampling, 3,809 serum samples were collected from 1,237 families in general population in the disease surveillance points in Fujian province. HBsAg, anti-HBs and anti-HBc were screened by RIA and HBeAg, anti-HAV, anti-HCV anti-HDV anti-HEV were by EIA. The results showed that the standardized prevalence rates of HAV, HBV, HCV, HDV, HEV, HBsAg, anti-HBs, anti-HBc and HBeAg were 76.60%, 77.26%, 3.99%, 2.10%, 18.80%, 17.25%, 34.33%, 68.58% and 8.42% respectively. The HAV, HBV, HEV prevalence rates in rural were higher than in urban areas. The HBsAg prevalence rate among males was higher than females, with peaks evidenced in 5-9 years old and 20-29 years old. There seemed to be significant family clusterings of HBV and HEV infection. There was higher HEV prevalence rate among the young-robusts but lower HAV prevalence rate among children in urban areas. These results suggested that Fujian is a highly prevalent area for HAV, HBV, HCV and HEV infections. Thus HA and HB vaccination should play as the most effective strategy in the prevention of HAV and HBV infections.
Zhao L, Al-Tubuly R, Sebkhi A, et al., 1996, Angiotensin II receptor expression and inhibition in the chronically hypoxic rat lung, British Journal of Pharmacology, Vol: 119, Pages: 1217-1222
1. Angiotensin II (AII) binding density and the effect of chronic AII receptor blockade were examined in the rat model of hypoxia-induced pulmonary hypertension. 2. [125I]-[Sar1,Ile2]AII binding capacity was increased in lung membranes from rats exposed to hypoxia (10% fractional inspired O2) for 7 days compared to normal rats (Bmax 108 +/- 12 vs 77 +/- 3 fmol mg-1 protein; P < 0.05), with no significant change in dissociation constant. Competition with specific AII receptor subtype antagonists demonstrated that AT1 is the predominant subtype in both normal and hypoxic lung. 3. Rats treated intravenously with the AT1 antagonist, GR138950C, 1 mg kg-1 day-1 rather than saline alone during 7 days of exposure to hypoxia developed less pulmonary hypertension (pulmonary arterial pressure: 21.3 +/- 1.7 vs 28.3 +/- 1.1 mmHg; P < 0.05), right ventricular hypertrophy (right/left ventricle weight ratio: 0.35 +/- 0.01 vs 0.45 +/- 0.01; P < 0.05) and pulmonary artery remodelling (abundance of thick-walled pulmonary vessels: 9.6 +/- 1.4% vs 20.1 +/- 0.9%; P < 0.05). 4. The reduction in cardiac hypertrophy and pulmonary remodelling with the AT1 antagonist was greater than that achieved by a dose of sodium nitroprusside (SNP) that produced a comparable attenuation of the rise in pulmonary arterial pressure during hypoxia. 5. The data suggest that AII, via the AT1 receptor, has a role in the early pathogenesis of hypoxia-induced pulmonary hypertension in the rat.
Zhao L, Brown LA, Owji AA, et al., 1996, Adrenomedullin activity in chronically hypoxic rat lungs, American Journal of Physiology - Heart and Circulatory Physiology, Vol: 40, ISSN: 0363-6135
Adrenomedullin (AM) is a novel vasodilator with structural similarities to calcitonin gene-related peptide (CGRP). This study investigated AM activity in the rat lung during hypoxia-induced pulmonary hypertension. Both rat AM (0.2-10 nmol) and α-CGRP (0.2-2 nmol) produced dose-related reductions in pulmonary artery pressure in the isolated perfused lung ventilated with 2% O 2 . Pretreatment with α-CGRP, which demonstrated tachyphylaxis, or its antagonist, CGRP-(8-37), reduced the hypotensive response to AM, suggesting that part of the response to AM is mediated by CGRP receptors. 125 I-labeled AM and 125 I-labeled CGRP binding was significantly increased in lung membranes from 7-day hypoxic animals (AM from 1.94 ± 0.3 to 3.36 ± 0.4 and CGRP from 0.06 ± 0.01 to 0.12 ± 0.02 pmol/mg protein), with no change in dissociation constant. Moreover, the hypotensive response to both peptides was increased in the lungs of 7-day hypoxic rats. There was no significant change in lung immunoreactive AM concentrations (hypoxic 5.04 ± 0.48 vs. control 6.28 ± 0.76 pmol/g wet wt of tissue) or steady-state AM mRNA levels in 7-day hypoxic rats. Nonetheless, AM may be useful for the acute pharmacological manipulation of pulmonary artery pressure in hypoxiainduced pulmonary hypertension. Copyright © 1996 the American Physiological Society.
Zhao L, Brown LA, Owji AA, et al., 1996, Adrenomedullin activity in chronically hypoxic rat lungs, AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, Vol: 271, Pages: H622-H629, ISSN: 0363-6135
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- Citations: 38
Zhao L, Brown LA, Owji AA, et al., 1996, Adrenomedullin activity in chronically hypoxic rat lungs, American Journal of Physiology - Heart and Circulatory Physiology, Vol: 271, ISSN: 0363-6135
Adrenomedullin (AM) is a novel vasodilator with structural similarities to calcitonin gene-related peptide (CGRP). This study investigated AM activity in the rat lung during hypoxia-induced pulmonary hypertension. Both rat AM (0.2-10 nmol) and (α-CGRP (0.2-2 nmol) produced dose-related reductions in pulmonary artery pressure in the isolated perfused lung ventilated with 2% O2. Pretreatment with α-CGRP, which demonstrated tachyphylaxis, or its antagonist, CGRP-(8-37), reduced the hypotensive response to AM, suggesting that part of the response to AM is mediated by CGRP receptors. 125I-labeled AM and 125I-labeled CGRP binding was significantly increased in lung membranes from 7-day hypoxic animals (AM from 1.94 ± 0.3 to 3.36 ± 0.4 and CGRP from 0.06 ± 0.01 to 0.12 ± 0.02 pmol/mg protein), with no change in dissociation constant. Moreover, the hypotensive response to both peptides was increased in the lungs of 7-day hypoxic rats. There was no significant change in lung immunoreactive AM concentrations (hypoxic 5.04 ± 0.48 vs. control 6.28 ± 0.76 pmol/g wet wt of tissue) or steady-state AM mRNA levels in 7-day hypoxic rats. Nonetheless, AM may be useful for the acute pharmacological manipulation of pulmonary artery pressure in hypoxia-induced pulmonary hypertension.
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