D L Zhu

Shanghai Medical University, Shanghai, Shanghai Shi, China

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Publications (28)100.13 Total impact

  • PJ Gao · ZQ Che · DL Zhu

    No preview · Conference Paper · May 2005
  • Y. Li · J. G. Wang · G. L. Wang · YS Qian · P. J. Gao · JA Staessen · D. L. Zhu

    No preview · Article · Jun 2004 · Journal of Hypertension
  • Y. Li · P. J. Gao · G. L. Wang · D. L. Zhu

    No preview · Article · Jun 2004 · Journal of Hypertension

  • No preview · Article · Feb 2004 · Journal of Hypertension
  • A J Sun · P J Gao · J J Liu · K D Ji · D L Zhu
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    ABSTRACT: To identify the genes that are differentially expressed during the phenotypic transition from vascular adventitial fibroblasts to myofibroblasts, the adventitial fibroblasts were cultured from rat thoracic aorta, and myofibroblasts were obtained by treatment of fibroblasts with TGF-beta1. Differential display PCR (DD-PCR) was used to screen for differentially expressed genes by comparison of mRNA extracted from the two cell populations. Bands upregulated or downregulated on DD gels were excised, reamplified, cloned and sequenced. DD results were verified by quantitative PCR and Northern blot analysis.Antisense oligonucleotide was transfected to study the effect of osteopontin on migration of AF. Differential display showed a significant difference in gene expression profile between the two cell types. A transcript that was downregulated in myofibroblasts showed high DNA sequence homology to part of the gene for NADH dehydrogenase subunit 5. An upregulated transcript showed significant sequence homology to osteopontin gene. Quantitative PCR and Northern blot analysis confirmed the DD results. Among the other differential bands detected, 4 candidate sequences showed no homology to the known genes. The AF numbers of migration were significantly decreased by use of OPN antisense oligonucleotide. This study suggests that the downregulation of gene encoding NADH dehydrogenase subunit 5 and upregulation of osteopontin gene and several other unknown genes may be involved in the phenotypic transition of adventitial fibroblasts to myofibroblats. Inhibition of the expression of OPN may play an important role in the process of vascular remodeling.
    No preview · Article · Jan 2002 · Sheng li xue bao: [Acta physiologica Sinica]
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    ABSTRACT: Adducin is a membrane skeletal protein that is involved in the regulation of membrane ion transport and cellular signal transduction. Essential hypertension has been linked to alpha-adducin gene locus, and association of a polymorphism of the gene has been found in some studies, but results of linkage or association studies on alpha-adducin gene are controversial among different populations. This study was designed to examine the linkage between alpha-adducin gene locus and essential hypertension and to reveal the relationship between an alpha-adducin gene polymorphism (Gly460Trp) and essential hypertension in a Chinese population. For the linkage study, one hundred and six Chinese nuclear families were recruited, including 417 hypertensive patients in all 474 individuals. Those samples were genotyped at D4S412 and D4S3038. The distances between the two microsatellite markers and the alpha-adducin gene locus are less than 3cM. Parametric, non-parametric linkage (NPL) analyses using the GENEHUNTER software were carried out. Sib transmission-dise- quilibrium test (S-TDT), as well as transmission-disequilibrium test (TDT). was also implemented with TDT/S-TDT Program 1.1. Serum levels of uric acid, creatinine, blood urea nitrogen (BUN), fasting glucose and lipids were determined as phenotypes. In an association study, 138 hypertensive and 121 normotensive subjects were genotyped at Gly460Trp of the alpha-adducin gene to examine a possible association between this polymorphism and blood pressure or other phenotypes. We fail to find the linkage between the two markers and essential hypertension by parametric, NPL analysis or TDT/S-TDT study. With the use of the simple association and the multivariate logistic regression analyses, we also fail to reveal a significant association between the Gly460Trp polymorphism in alpha-adducin gene and the blood pressure variation, or blood biochemical indices studied. The frequency of the 460Trp allele in Chinese (46-48%) is similar to that found in Japanese (54-60%) while the allele frequency is less common in Caucasian (13%-23%). These findings suggest that in our Chinese population, alpha-adducin 460Trp variant may not play an important role in the etiology of EH. And the negative results of linkage and TDT/ S-TDT further supports this conclusion.
    No preview · Article · Nov 2001 · Clinical and Experimental Hypertension
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    YH Ke · B Su · XF Song · DR Lu · LF Chen · HY Li · CJ Qi · S Marzuki · R Deka · P Underhill · [...] · D Wallace · R S Wells · M Seielstad · P Oefner · DL Zhu · JZ Jin · W Huang · R Chakraborty · Z Chen · L Jin ·
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    ABSTRACT: To test the hypotheses of modern human origin in East Asia, we sampled 12,127 male individuals from 163 populations and typed for three Y chromosome biallelic markers (YAP, M89, and M130). All the individuals carried a mutation at one of the three sites. These three mutations (YAP+, M89T, and M130T) coalesce to another mutation (M168T), which originated in Africa about 35,000 to 89,000 years ago. Therefore, the data do not support even a minimal in situ hominid contribution in the origin of anatomically modern humans in East Asia.
    Full-text · Article · Jun 2001 · Science
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    ABSTRACT: The abnormal proliferation of vascular smooth muscle cells (VSMCs) is closely related to vascular diseases. There is growing evidence that calcium antagonists inhibit VSMC growth/proliferation, yet their molecular mechanisms remain to be determined. Recent reports suggest that p42/p44 mitogen-activated protein kinases (MAPKs) play an important role in cell growth and proliferation induced by growth factors. This study was designed to determine whether these MAPKs are involved in VSMC proliferation induced by basic fibroblast growth factor (bFGF) and to examine the inhibitory effect of amlodipine. Human VSMCs were obtained from inner mammary artery. p42/p44 MAPKs activity was measured by immunoblotting assay using anti-p42/p44 phospho-MAPK antibody. 1) bFGF (20 ng/ml) significantly activated p42/p44 MAPKs with a peak time of 5-15 min, which was maintained for 3 h. PD98059 (100 nM-10 microM), a specific inhibitor of MAPK kinase, inhibited bFGF-induced p42/p44 MAPKs activation in a dose-dependent manner. 2) Amlodipine (1-100 nM) dose-dependently inhibited p42/p44 MAPKs activation by bFGF. 3) Amlodipine (10 nM) could inhibit both short-term and long-term p42/p44 MAPKs activation by bFGF. Our results indicate that bFGF could activate p42/p44 MAPKs. Amlodipine, which could inhibit bFGF-induced human VSMC proliferation, inhibited both short-term and sustained p42/p44 MAPKs activation by bFGF, suggesting that bFGF-induced VSMC proliferation may be related to p42/p44 MAPKs activation, and that the antiproliferative effect of amlodipine may be related to its inhibition of p42/p44 MAPKs activation.
    No preview · Article · Aug 2000 · Hypertension Research
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    ABSTRACT: The replication and activation of both vascular smooth muscle cells and macrophages, which have previously entered the arterial wall, are key events in the atherosclerotic process. The importance of macrophage colony-stimulating factor (MCSF) in control of the growth/proliferation of both cell types confers to this compound a central role in the development of vascular lesions. In order to gain insight into the mechanisms of macrophage proliferation, we investigated the effect of MCSF upon the proliferation of DEL cells. DEL cells constitute a monocyte/histiocytic cell line that differentiates along a macrophage lineage following exposure to phorbol ester. DEL cells constitutively express MCSF, and its receptor MCSFR is encoded by c-fms. We examined whether MCSF might play a role in the proliferation of cultured DEL cells. [3H]Thymidine or 5-bromo-2-deoxyuridine (BrdU) incorporation was measured following the addition of recombinant MCSF or L929 cell supernatant (as a source of MCSF) to quiescent DEL cells. In DEL cells, serum-free L929 cell supernatant induced DNA synthesis in a dose-dependent manner, and such an effect could be blunted by pretreatment of L929 cell supernatant with anti-mouse MCSF antibody. In these cells, DNA synthesis could also be triggered in a dose-dependent manner by the addition of recombinant human MCSF (rh MCSF) or thrombin. These findings clearly show that MCSF influences DEL cell proliferation and suggest an autocrine loop activation. They indicate that MCSF plays an important role in the development of vascular lesions, which occur during atherosclerotic progression.
    No preview · Article · Aug 2000 · Hypertension Research
  • D L Zhu · J Gogusev · P Marche
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    ABSTRACT: The resulats of this study are as follows. (1) As measured by a bioassay, a macrophage colony-stimulating activity was detected in the serum-free conditioned medium of rat aortic vascular smooth muscle cells (VSMCs), which could be subdued by the addition of specific anti macrophage colony-stimulating factor (MCSF) antibody. (2) The presence of MCSF receptor was confirmed by immunocytochemistry using a specific anti c-Fms antibody. (3) The presence of mRNAs for MCSF and c-fms (which encoded MCSF receptor) was determined by Northern blot analysis. Their expressions were detectable in quiescent VSMCs and markedly increased after addition of serum. These data demonstrated for the first time the production of MCSF and the presence of MCSF receptor in cultured rat VSMCs. It is suggested that MCSF might modulate VSMCs functions via both autocrine and paracrine mechanisms. Rat VSMCs appear to be a suitable cell model for studying the cell proliferation effect of MCSF.
    No preview · Article · May 1999 · Sheng li xue bao: [Acta physiologica Sinica]
  • P J Gao · D L Zhu · Y M Zhan · O Stepien · P Marche · G S Zhao
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    ABSTRACT: Cell growth and proliferation were evaluated in cultured vascular smooth muscle cells (VSMCs) isolated from spontaneously hypertensive rat (SHR) and normotensive Wistar-Kyoto (WKY) rat aortae by measuring [3H]-thymidine incorporation into newly synthesized DNA and by determining cell number, respectively. The results showed that in cultures from both rat strains (1) serum-, basic fibroblast growth factor (bFGF)- and thrombin-induced DNA synthesis were inhibited by L-phenylalanine dose-dependently; (2) L-phenylalanine inhibited cell proliferation in response to serum in a concentration-dependent manner; (3) L-phenylalanine inhibited serum-induced proto-oncogene c-fos and c-myc expression; (4) L-tyrosine, L-histidine and D-phenylalanine failed to mimic the inhibitory effect of L-phenylalanine. All these data demonstrate that L-phenylalanine could exert a direct and specific antiproliferative effect on VSMCs suggesting that such effect can account for the antihypertensive action of this amino acid observed in SHR.
    No preview · Article · Sep 1998 · Sheng li xue bao: [Acta physiologica Sinica]
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    ABSTRACT: Atherosclerosis, like several other vascular diseases, exhibits structural and functional abnormalities resulting partially from an exaggerated proliferation of vascular smooth-muscle cells (VSMCs). Ca2+ channel blockers, such as amlodipine, have been suggested to retard or even prevent the progression of atherosclerosis. To determine the mechanisms involved in these effects, we investigated the influence of amlodipine on VSMC proliferation by using rat aortic VSMCs in culture. Amlodipine (0.1-10 microM) inhibited serum-, basic fibroblast growth factor (bFGF)-, and thrombin-induced VSMC proliferation and DNA synthesis in a concentration-dependent manner, as demonstrated by cell count and bromodeoxyuridine (BrdU)-incorporation measurements, respectively. Delayed addition of amlodipine after VSMC stimulation showed that the drug exerted its effect early in G1 phase of the cell cycle. This observation was confirmed by the finding that amlodipine did not influence DNA synthesis in VSMCs arrested to the G1/S boundary by hydroxyurea treatment. Consistent with its effects on VSMC growth/proliferation, amlodipine also decreased c-myc, c-fos, and c-jun protooncogene expression induced by serum, thrombin, or bFGF within 1 h after cell activation, as assessed by semiquantitative reverse transcriptase (RT)-polymerase chain reaction (PCR) analysis. The calcium channel agonist Bay K 8644, which counteracted the inhibition by nifedipine of bFGF-, thrombin- or serum-induced DNA synthesis, was ineffective to antagonize the inhibitory effect of amlodipine. The aforementioned effects of amlodipine were of similar amplitude, irrespective of the growth-enhancing agent used. This strongly indicates that amlodipine acts downstream of receptor activation to exert its antiproliferative action, probably early in the G1 phase of the cell cycle. Moreover, the lack of antagonistic effect between amlodipine and Bay K 8644 suggests that, in addition to its L-type Ca2+ channel inhibitory effect, amlodipine inhibits other intracellular signaling pathways. Such an interference of amlodipine with mitogenic signaling pathways might contribute to confer a blood vessel-protecting potential on amlodipine.
    No preview · Article · Jun 1998 · Journal of Cardiovascular Pharmacology
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    ABSTRACT: Increased proliferation of intimal smooth muscle cells (SMCs), resulting in myointimal hyperplasia and luminal narrowing, is a characteristic of the early phase of atherogenesis. Since agents that reduce this process could potentially be considered as alternatives to lipid-lowering therapy in the prevention/treatment of atherosclerosis, it is of interest to elucidate the mechanisms involved in myointimal proliferation. This review focuses on the main mechanisms that control vascular SMC reactivity/proliferation with particular reference to spontaneously hypertensive rat-derived arterial cells, which exhibit exaggerated growth and hyperresponsiveness to stimuli compared with cells from normotensive Wistar-Kyoto rats. In view of the fact that overall cell reactivity is under the control of free Ca2+ ions, the beneficial effects of calcium antagonists on the prevention/treatment of atherosclerosis are discussed. In particular, the mechanisms whereby amlodipine--a vascular selective inhibitor of inward Ca2+ current carried by the L-type Ca2+ channels--can affect cell growth and exhibit antiatherogenic properties are reviewed.
    No preview · Article · Jan 1998 · International Journal of Cardiology
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    ABSTRACT: In both atherosclerosis and arterial hypertension, structural and functional abnormalities result in vascular hypertrophy that is associated with an increased ratio of vascular media thickness to lumen diameter and hyperreactivity of vascular smooth muscle cells (VSMCs), resulting in uncontrolled cell migration and growth in vivo. In culture, VSMCs isolated from the spontaneously hypertensive rat (SHR) also display exaggerated growth and/or proliferation compared to VSMCs isolated from normotensive control Wistar Kyoto (WKY) rats. In vitro studies of cultured VSMCs can therefore be used as a model to investigate the mechanisms whereby a drug such as amlodipine can exert its antihypertensive and antiatherogenic effects. The present in vitro investigations examine the mechanisms whereby amlodipine reduces VSMC growth/proliferation promoted by basic fibroblast growth factor (bFGF), a peptide growth factor likely to participate in the vascular smooth muscle hypertrophy of the SHR. VSMCs from SHR and/or WKY rat aortae were isolated, passaged, and cultured. The influence of amlodipine on VSMC growth/proliferation was studied by measuring DNA synthesis and cell number under experimental conditions, which allowed us to determine the cell cycle phase in which amlodipine exerts its effects. Amlodipine was found to inhibit growth and bFGF-induced DNA synthesis in a concentration-dependent manner. Delayed addition of amlodipine showed that the drug exerts its effect early in the G1 phase, a result that was confirmed by the finding that amlodipine could not inhibit bFGF-induced DNA synthesis in VSMCs arrested at the G1/S boundary. In comparative experiments, the inhibitory effect of amlodipine on both cell growth and DNA synthesis was found to be of similar magnitude in SHR- and WKY-derived VSMCs. It is therefore likely that by modulating cell growth/proliferation induced by bFGF, amlodipine may reduce the vascular hypertrophy of the SHR. Since amlodipine also has been found to inhibit VSMC migration, one may reasonably envisage that these characteristics are important components of the antiatherogenic properties of the drug.
    No preview · Article · Jan 1998 · International Journal of Cardiology
  • P. Marche · O. Stépien · L. Iouzalen · D. L. Zhu

    No preview · Article · Oct 1997 · Atherosclerosis
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    ABSTRACT: Am J Hypertens (1997) 10, 37A–37A; doi: 10.1016/S0895-7061(97)88769-9 C6: Inhibition of growth factor-induced vascular hypertrophy by amlodipine O. Stépien, D.L. Zhu, L. Iouzalen, T. Hérembert, J. Gogusev and P. Marche
    No preview · Article · Mar 1997 · American Journal of Hypertension
  • P Marche · T Herembert · D L Zhu
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    ABSTRACT: 1. In primary hypertension, an abnormally high vascular resistance can be explained in terms of alterations in vessel wall structure. Arterial cell hypertrophy and/or hyperplasia have been implicated as playing a central role in the vascular abnormalities noted in spontaneously hypertensive rats (SHR). Cultured arterial cells appear therefore as attractive models for studying m vitro the mechanisms whereby cells originating from hypertensives exhibit hyperproliferation and/or hyper-responsiveness. 2. This review summarized our present knowledge on growth and related biochemical events of cultured SHR-derived vascular smooth muscle cells or aortic adventitial fibroblasts, in response to various polypeptide growth factors and vasoactive agents. 3. Exaggerated growth response to various mitogens in cultured SHR-derived vascular cells has been well documented. However, the molecular mechanisms of abnormal growth in SHR remain unknown. This abnormality seems not to be a consequence of the alterations at the levels of receptors or of some key mitogenic events of early signalling pathways such as phospholipase C, protein kinase C and G-proteins. Further studies should therefore focus on the more distal events related to cell growth.
    No preview · Article · Jan 1996 · Clinical and experimental pharmacology & physiology. Supplement
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    T Hérembert · D L Zhu · P Marche
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    ABSTRACT: 1. To gain insight into the parameters which control vascular structure, we investigated the mechanisms whereby nifedipine, and other dihydropyridines, inhibit the growth of cultured fibroblasts isolated from the adventitia of the aorta of spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats. 2. The effects of nifedipine on cell proliferation and on serum-induced DNA synthesis were determined by measuring the cell number and the incorporation of [3H]-thymidine, respectively. The mechanism of action of nifedipine was studied by adding the drug either to randomly growing cells or to quiescent, G0/G1 arrested and synchronized cells. The effects of varying the duration of drug treatment were also examined. 3. In randomly growing cultures nifedipine, like other dihydropyridines concentration-dependently inhibited cell proliferation; the rank order of effect (measured at a concentration of 10 microM) was nifedipine > nisoldipine > nitrendipine approximately nimodipine. 4. In G0/G1 arrested cell cultures, nifedipine concentration-dependently inhibited serum-induced [3H]-thymidine incorporation. In this respect it had similar effects in cell cultures from WKY and SHR. In both SHR and WKY cultures, nifedipine delayed the transition from G0/G1 to S phase, and inhibited serum-induced DNA synthesis possibly by acting on the early G1 phase. 5. In cell cultures from both SHR and WKY, serum-induced DNA synthesis was similarly (approximately 40%) inhibited after a 1 day treatment with 10 microM nifedipine. In contrast, after 5 days treatment with the drug, the inhibition of DNA synthesis was approximately 65% and approximately 10% in SHR and WKY cultures, respectively. The inhibitory effects of nifedipine against proliferation of fibroblasts were 25% and 60%, respectively,after 1 and 5 days of treatment, and were similar in cells derived from SHR and WKY. This indicates that 5 days treatment with nifedipine inhibited the proliferation of SHR and WKY fibro blasts by acting mostly on the early G1 phase and the M phase, respectively.6. Irrespective of the duration of treatment (1 or 5 days) with 10 microM nifedipine, the inhibition of DNA synthesis could be abolished and partially reduced by Bay K 8644 (1 microM) in WKY and SHR fibroblasts,respectively. In cell cultures from both SHR and WKY the inhibitory effects of a short term and of along term treatment with nifedipine against cell proliferation were reduced and unaffected, respectively by Bay K 8644.7. These results indicate that nifedipine inhibited cell proliferation and serum-induced DNA synthesis by altering the cell cycle through different mechanisms in SHR and WKY fibroblasts. They also suggest the existence in aortic fibroblasts of interactions between calcium channel blockers of the dihydropyridine series and the mitogenic signalling pathways of growth factors contained in serum.
    Preview · Article · May 1995 · British Journal of Pharmacology
  • T Hérembert · P Marche · DL Zhu

    No preview · Article · Apr 1995
  • P. Marche · J. Gogusev · D. L. Zhu
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    ABSTRACT: Introduction: The administration of recombinant erythropoietin (rHuEpo) to anaemic chronic renal failure patients may be associated with an increase in blood pressure, possibly by direct effects on peripheral blood vessels. In the present study, experiments were designed to explore the hypothesis that rHuEpo could enhance vascular resistance by a mitogenic effect on vascular smooth muscle cells (VSMQ, and mat pre-existing hypertension might be a predisposing condition. Methods: Cultured VSMC from the thoracic aortae of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were studied for DNA synthesis, phospholipase C activity, and cell growth-related protooncogene expression in the presence of rHuEpo. Results: In cells from both strains, rHuEpo dose-dependently increased DNA syndiesis and stimulated phospholipase C activity, as indicated by 3H-thymidine incorporation and 3H-inositol phosphate formation, respectively (median effective concentration +/- 4 U/ml). Exposure of VSMC to rHuEpo for various times gradually increased the levels of c-myc and JunB and transiendy induced c-fos expression, as determined by Northern analysis. rHuEpo-induced DNA synthesis was markedly enhanced in VSMC from SHR compared with those from WKY rats. In contrast, rHuEpo-induced phospholipase C activity and proto-oncogene expression was similar in the two strains. Conclusions: Taken together, these results suggest that rHuEpo may function as a VSMC growth-promoting factor through activation of the phospholipase C cascade and modulation of protooncogene expression. It could thereby contribute to vascular hypertrophy and arterial hypertension.
    No preview · Article · Sep 1994 · Journal of Hypertension

Publication Stats

405 Citations
100.13 Total Impact Points

Institutions

  • 2004
    • Shanghai Medical University
      Shanghai, Shanghai Shi, China
    • Shanghai Ruijin Hospital
      Shanghai, Shanghai Shi, China
  • 2000-2002
    • Ruijin Hospital North
      Shanghai, Shanghai Shi, China
  • 1992-1996
    • Université René Descartes - Paris 5
      Lutetia Parisorum, Île-de-France, France