D L Zhu

Ruijin Hospital North, Shanghai, Shanghai Shi, China

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Publications (34)65.42 Total impact

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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.
    Sheng li xue bao: [Acta physiologica Sinica] 01/2002; 53(6):435-9.
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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.
    Clinical and Experimental Hypertension 11/2001; 23(7):579-89. · 1.28 Impact Factor
  • K X Zhang, D L Zhu, W Huang
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    ABSTRACT: Genes underlie numerous human diseases and traits. Although we have witnessed a great deal of success in identifying disease-susceptible genes, the task remains challenging for most of the complex diseases. This paper reviews evidence for the role of genetic factors in complex diseases, and strategies that can potentially optimize our chance of success in identifying genes involved in complex diseases. Advances in molecular biology, particularly mapping of the human genome, statistical methods that provide more accurate models of complex patterns of inheritance, and advances in basic medical science, which have increased our understanding of disease pathophysiology, will ultimately strengthen the ability of the current generation of genetic epidemiological studies to identify the genetic basis of complex human disorders.
    Sheng li ke xue jin zhan [Progress in physiology] 08/2001; 32(3):215-9.
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    ABSTRACT: To screen the gene mutation in beta and gamma subunits of the epithelial sodium channel (ENaC) of a Chinese family, some of whose members are clinically diagnosed as suffering from Liddle syndrome. Twelve family members were recruited to the study. Among them, two brothers had been clinically diagnosed as suffering from Liddle syndrome. Peripheral blood samples were collected from all members of the family and total genomic DNA was prepared for genetic analysis. Polymerase chain reaction (PCR) was used for amplifying the last exon of beta (codon 513-673) and gamma (codon 503-632) subunits of the ENaC gene. PCR products were purified and subjected to a direct DNA sequence analysis. Genetic analysis of the beta ENaC gene revealed a missense mutation of CCC to CTC at codon 616 in four middle-aged men of the second generation and one young woman of the third generation. There was no mutation of the gamma ENaC gene in any of the individuals examined. Through direct DNA sequencing analysis, we diagnosed the disease present in five members of a Chinese family as Liddle syndrome, and excluded it in some other young offspring suffering from the monogenic disease. Our results provide further evidence that Pro616 is a critical amino acid that has a key role in the inhibition of sodium channel activity.
    Journal of Hypertension 06/2001; 19(5):885-9. · 3.81 Impact Factor
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    ABSTRACT: To identify chromosome regions containing hypertension susceptibility genes in Chinese. A three-stage study was carried out in Chinese siblings ascertained through outpatient clinics. In the first stage, 283 affected sib-pairs from 79 nuclear families were subjected to a genome-wide scan with 240 microsatellite marker loci. The second stage focused on chromosome 2 with additional markers resulting in an average distance of 5 cM and used an independent sample of 637 affected sib-pairs from 161 families. In the third stage, a fine-scale mapping study on the suggestive region was performed in an independent set of 777 affected sib-pairs from 106 families. Fourteen markers were used with an average distance less than 2 cM. Non-parametric linkage analyses (NPL), parametric linkage analyses and transmission-disequilibrium tests were used to assess evidence for linkage and association. Three markers (D2S168 at 27.06 cM, D2S151 at 152.04 cM and D2S142 at 161.26 cM) on chromosome 2 with suggestive linkage to hypertension susceptibility genes were identified in the genome-wide scan. In stage II, the suggestive region around D2S151 and D2S142 was replicated, while the linkage around D2S168 was not. In the stage III fine-scale mapping study, multipoint linkage analyses showed LOD scores greater than 2.0 throughout a region between 157.16 cM and 162.46 cM (all P < 0.001) with a maximum peak of 2.24 (P= 0.00067) at 160.52 cM. We also observed a NPL Z-score peak of 3.27 at 157.55 cM (P= 0.00086). The results of a suggestive region on chromosome 2q14-q23 (D2S112-D2S2370) were consistent between each of the three studies. Interestingly, this region overlaps a syntenic region that contains blood pressure quantitative trait loci identified in rat models of hypertension. These data suggest that the region near D2S142 and D2S151 deserves to be further screened for hypertension susceptibility genes.
    Journal of Hypertension 01/2001; 19(1):55-61. · 3.81 Impact Factor
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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.
    Hypertension Research 08/2000; 23(4):403-6. · 2.79 Impact Factor
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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.
    Hypertension Research 08/2000; 23(4):399-401. · 2.79 Impact Factor
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    ABSTRACT: A total of 1.1 kb including whole ITS (intertranscribed spacer), part of 5.8S rDNA and 2S rDNA were sequenced. The results reveal that D. pallidifrons, Taxon I and Taxon J share the same sequence, and D. albomicans and D. s. neonasuta have the other same one. Among the sequences, there were a handful of insertions, deletions and substitutions. Insertions and deletions occur mainly between outgroup and ingroups; yet only 1 insertion and 12 deletions were detected in D. niveifrons, and 1 deletion was found in D. s. sulfurigaster. Among all the substitutions in outgroup and ingroups, totally 55 transitions and 65 transvertions were detected. The value of transition transvertion is quite different to that of mitochondrial genome. We applied parsimony and NJ methods to reconstruct the phylogenetic relationships of the 7 taxa. They show that D. niveifrons is on the basis of the trees, which suggests that it be less related to the rest; D. albomicans, D. s. neonasuta, D. pallidifrons, Taxon I and Taxon J are more related. We suggested that more related topology of D. s. sulfurigaster and D. s. neonasuta due to the specific evolution of ITS, yet not meaning their real relationships. Sequence variations and phylogeny analysis reveal that the ITS may be not an informative marker to nasuta subgroup. However, secondary structure analysis by using PCFOLD 4.0 reveals that the structure of the ITS is quite conservative; the stem-loop of ITS 3'-end may be an important structure of rDNA splicing.
    Acta Genetica Sinica 02/2000; 27(1):18-25.
  • X Li, B X Ji, D L Zhu, Z C Geng, R Y Chu
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    ABSTRACT: The second exons of the HLA-DQB1 genes in 55 patients with Pathological Myopia were amplified and then digested with ApaI, Bsp1286I, BsaHI, BssHII, HaeII, HaeIII, HpaII, RsaI to determinate the genotypes and the allele frequencies. Among the 16 alleles, HLA-DQB1*0201, *0301, *0303, *0401 alleles in PM patients differed significantly from that of the normal ones in the distribution of the alleles, and seemed to be the pathogenic genes (P < 0.05; AF = 0.1636, 0.1091, 0.1636, 0.1091 vs. 0.0400, 0.0300, 0.0400, 0.0200; RR = 4.2886, 3.5350, 4.2890, 5.0000); While the HLA-DQB1*0601, *0602 frequencies in PM patients were remarkably lower than that of the normal ones, which showed the property of protective genes (Pc = 0.0000, AF = 0.1182, 0.0818 vs. 0.4300, 0.3100). DQB1*05.32, *0504 and *0605 can not be detected. The association of PM with DQB1 was found for the first time in the world, which has great significance both to theoretical study and to clinical diagnosis.
    Acta Genetica Sinica 02/2000; 27(3):189-94.
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    ABSTRACT: In this study, the region corresponding to the Thr-Gly region of the period (per) gene in the Drosophila nasuta subgroup of species was sequenced. The results showed that this region was highly conserved in the D. nasuta subgroup. There were only nine variable sites found in this 300-bp-long region, all located in two small regions highly variable among Drosophila species. No length variation was observed either within this subgroup or in the Yunnan (YN) population of D. albomicans. The deduced amino acid sequences were identical for all 14 taxa in the D. nasuta subgroup, and a stretch of alternating Thr-Gly pairs was not observed in this subgroup. A phylogenetic tree was constructed. The clustering of some species was in general agreement with previous works, but it also raised some question on the phylogenetic relationship between the nasuta species. The data did not implicate the Thr-Gly region playing a role in behavioral isolation in this subgroup of Drosophila.
    Journal of Molecular Evolution 10/1999; 49(3):406-10. · 2.15 Impact Factor
  • 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.
    Sheng li xue bao: [Acta physiologica Sinica] 05/1999; 51(2):181-6.
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    ABSTRACT: Myasthenia Gravis (MG) is an autoimmune disease which is a neuromuscular disorder of autoimmune origin. MG in different races or ethnic groups has different genetic susceptibility. To search for the associations of MG in the Chinese patients with HLA-DQ molecules, PCR-RFLP method was employed for genotyping HLA-DQA1 and -DQB1 genes of MG patients and the normal Chinese. The distributions of alleles of DQA1 and DQB1 in the normal Chinese and the MG patients were listed. The DQB allele, DQB1 * 0302 was positively associated with MG (RR = 2.990, Pc = 0.0307), and a negative association was found for DQA1 * 0501 (RR = 0.4166, Pc = 0.0315). DQ haplotype DQA1 * 0301-DQB1 * 0302 was significantly increased in patients when compared to controls (RR = 7.727, Pc = 0.0109).
    Acta Genetica Sinica 02/1999; 26(4):295-300.
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    ABSTRACT: In this paper we analysed the RFLP of mtDNA in Lanzhou (LZ) population of D. virilis. By reanalysing the RFLP data of our previous work on other natural populations of D. virilis, a phylogenetic tree was produced based on the UPGMA method. It shows three main clusters: the Northern populations (LZ QD), the East China populations (NJ, SH, NB) and the Southern population (QZ). With the mtDNA's RFLP data and the results of our former work on allozyme variation in natural populations of D. virilis, we suggest that there exists a latitudinal cline of genetic variation in natural populations of D.virilis. The mechanism for the maintenance of the observed latitudinal pattern is discussed.
    Acta Genetica Sinica 02/1999; 26(3):198-202.
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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.
    Sheng li xue bao: [Acta physiologica Sinica] 09/1998; 50(4):401-8.
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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.
    Journal of Cardiovascular Pharmacology 06/1998; 31(5):786-93. · 2.38 Impact Factor
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    ABSTRACT: HLA-DQA1 and -DQB1 genes were investigated in two Chinese minor natinalities, Uygur and Kazak using PCR-RFLP genotyping method. Of the 8 DQA1 alleles, DQA1 *0301 was the most common in Uygurs and Kazaks. DQA1 *0401 and *0601 were the rarest alleles in Uygurs and *0601 in Kazaks. Of the 16 DQB1 alleles tested, DQB1 *0201 and *0301 were the most frequent alleles in Uygurs and Kazaks. DQB1 *0502, *05032 and *0504 in Uygurs, *05032, *0504 and *0605 in Kazaks were absent. Neither DQA1 nor DQB1 difference was found between the two populations. From the phylogenetic tree based on the gene frequencies of HLA-DQA1 and -DQB1 in Uygur, Kazak and other 25 related ethnic groups, we suggest that Uygurs and Kazaks have a closer relationship, and they are closer to Mongoloid, not Caucasoid.
    Acta Genetica Sinica 02/1998; 25(3):193-8.
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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.
    International Journal of Cardiology 01/1998; 62 Suppl 2:S79-84. · 5.51 Impact Factor
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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.
    International Journal of Cardiology 01/1998; 62 Suppl 2:S17-22. · 5.51 Impact Factor
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    ABSTRACT: Since in several vascular diseases abnormal vascular smooth-muscle cell (VSMC) proliferation is often associated with the presence of macrophages, we examined whether macrophage-colony-stimulating factor (M-CSF) might play a role in the control of VSMC growth. VSMCs were isolated from rat aorta and maintained in culture. Using a bioassay, a macrophage-colony-stimulating activity was detected in the serum-free supernatant of VSMCs, which could be inhibited by the addition of specific anti-M-CSF antibodies. The presence of M-CSF receptor protein and of M-CSF and M-CSF receptor gene transcripts was demonstrated by immunocytochemistry, using a specific anti-c-Fms antibody and Northern blot analysis respectively. [3H]Thymidine incorporation was measured following the addition to quiescent VSMCs of various dilutions of L929 cell supernatant (as a source of M-CSF) or of recombinant M-CSF. Both exogenous M-CSF and serum-free VSMC conditioned medium promoted DNA synthesis in a concentration-dependent manner, and this effect could be abrogated by the presence of a specific anti-M-CSF antibody. Under similar experimental conditions, L929 cell supernatant modulated proto-oncogene expression, as assessed by Northern blot analysis of c-fos, c-myc, egr-1 and junB. It was further demonstrated that M-CSF could act in synergy with thrombin, platelet-derived growth factor or basic fibroblast growth factor in promoting VSMC DNA synthesis. These results support the hypothesis that M-CSF affects the growth of cultured rat VSMCs through paracrine/autocrine mechanisms. Its effects at both the macrophage and the VSMC level confer to M-CSF a central role in the development of vascular lesions that occurs during atherosclerotic progression.
    Biochemical Journal 08/1997; 325 ( Pt 1):123-8. · 4.65 Impact Factor
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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
    American Journal of Hypertension 03/1997; · 3.67 Impact Factor

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223 Citations
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65.42 Total Impact Points

Institutions

  • 1999–2002
    • Ruijin Hospital North
      Shanghai, Shanghai Shi, China
  • 2001
    • Chinese National Human Genome Center at Shanghai
      Shanghai, Shanghai Shi, China
  • 2000
    • Kunming Institute of Zoology CAS
      Yün-nan, Yunnan, China
  • 1998–1999
    • Fudan University
      • Institute of Genetics
      Shanghai, Shanghai Shi, China
  • 1992–1998
    • Université René Descartes - Paris 5
      Lutetia Parisorum, Île-de-France, France
    • Unité Inserm U1077
      Caen, Lower Normandy, France