Biomedical subjects

Y Sun

Publications and source records attributed to Y Sun.

At least 595 records · Page 33Linked to original sources

PubMed1997

Two orphan seven-transmembrane segment receptors which are expressed in CD4-positive cells support simian immunodeficiency virus infection.

Clinical isolates of primate immunodeficiency viruses, including human immunodeficiency virus type 1 (HIV-1), enter target cells by sequential binding to CD4 and the chemokine receptor CCR5, a member of the seven-transmembrane receptor family. HIV-1 variants which use additional chemokine receptors are present in the central nervous system or emerge during the course of infection. Simian immunodeficiency viruses (SIV) have been shown to use CCR5 as a coreceptor, but no other receptors for these viruses have been identified. Here we show that two orphan seven-transmembrane segment receptors, gpr1 and gpr15, serve as coreceptors for SIV, and are expressed in human alveolar macrophages. The more efficient of these, gpr15, is also expressed in human CD4(+) T lymphocytes and activated rhesus macaque peripheral blood mononuclear cells. The gpr15 and gpr1 proteins lack several hallmarks of chemokine receptors, but share with CCR5 an amino-terminal motif rich in tyrosine residues. These results underscore the potential diversity of seven-transmembrane segment receptors used as entry cofactors by primate immunodeficiency viruses, and may contribute to an understanding of viral variation and pathogenesis.

Amino Acid Sequence↗

PubMed1997

A comparison of murine and human factor XI.

Factor XI is a plasma glycoprotein that is required for contact activation initiated fibrin formation in vitro and for normal hemostasis in vivo. In preparation for developing a mouse model of factor XI deficiency to facilitate investigations into this protease's contributions to coagulation, we cloned the complementary DNA for murine factor XI, expressed the protein in a mammalian expression system, and compared its properties with human recombinant factor XI. The 2.8-kb murine cDNA codes for a protein of 624 amino acids with 78% homology to human factor XI. Both recombinant murine and human factor XI are 160 kD homodimers comprised of two 80 kD polypeptides connected by disulfide bonds. Murine factor XI shortens the clotting time of human factor XI deficient plasma in an activated partial thromboplastin time assay, with a specific activity 50% to 70% that of the human protein. In a purified system, murine factor XI is activated by human factor XIIa and thrombin in the presence of dextran sulfate. Murine factor XI differs from human factor XI in that it undergoes autoactivation slowly in the presence of dextran sulfate. This is due primarily to murine factor XIa preferentially cleaving a site on zymogen factor XI within the light chain, rather than the activation site between Arg371 and Val372. Northern blots of polyadenylated messenger RNA show that murine factor XI message is expressed, as expected, primarily in the liver. In contrast, messenger RNA for human factor XI was identified in liver, pancreas, and kidney. The studies show that murine and human factor XI have similar structural and enzymatic properties. However, there may be variations in tissue specific expression and subtle differences in enzyme activity across species.

Amino Acid Sequence↗

PubMed1997

A multivalent PDZ-domain protein assembles signalling complexes in a G-protein-coupled cascade.

How are signalling molecules organized into different pathways within the same cell? In Drosophila, the inaD gene encodes a protein consisting of five PDZ domains which serves as a scaffold to assemble different components of the phototransduction cascade, including the principal light-activated ion channels, the effector phospholipase C-beta and protein kinase C. Null inaD mutants have a dramatically reorganized subcellular distribution of signalling molecules, and a total loss of transduction complexes. Also, mutants defective in a single PDZ domain produce signalling complexes that lack the target protein and display corresponding defects in their physiology. A picture emerges of a highly organized unit of signalling, a 'transduclisome', with PDZ domains functioning as key elements in the organization of transduction complexes in vivo.

Amino Acid Sequence↗

PubMed1997

Chronic expression of murine flt3 ligand in mice results in increased circulating white blood cell levels and abnormal cellular infiltrates associated with splenic fibrosis.

The effect of chronic expression of flt3 ligand (FL) on in vivo hematopoiesis was studied. Retroviral vector-mediated gene transfer was used in a mouse model of bone marrow transplantation to enforce expression of mouse FL cDNA in hematopoietic tissues. As early as 2 weeks posttransplantation, peripheral blood white blood cell counts in FL-overexpressing recipients were significantly elevated compared with controls. With the exception of eosinophils, all nucleated cell lineages studied were similarly affected in these animals. Experimental animals also exhibited severe anemia and progressive loss of marrow-derived erythropoiesis. All of the FL-overexpressing animals, but none of the controls, died between 10 and 13 weeks posttransplantation. Upon histological examination, severe splenomegaly was noted, with progressive fibrosis and infiltration by abnormal lymphoreticular cells. Abnormal cell infiltration also occurred in other organ systems, including bone marrow and liver. In situ immunocytochemistry on liver sections showed that the cellular infiltrate was CD3+/NLDC145+/CD11c+, but B220- and F4/80-, suggestive of a mixed infiltrate of dendritic cells and activated T lymphocytes. Infiltration of splenic blood vessel perivascular spaces resulted in vascular compression and eventual occlusion, leading to splenic necrosis consistent with infarction. These results show that FL can affect both myeloid and lymphoid cell lineages in vivo and further demonstrate the potential toxicity of in vivo treatment with FL.

Animals↗

PubMed1997

Differential functional significance of AP-1 binding sites in the promoter of the gene encoding mouse tissue inhibitor of metalloproteinases-3.

Tissue inhibitor of metalloproteinases-3 (TIMP-3) is an extracellular-matrix-associated protein that suppresses tumorigenicity or invasion in several model systems. We have identified, by in vitro footprinting, six AP-1 (activator protein-1) or AP-1-like binding sites in the mouse TIMP-3 promoter that bind purified c-Jun homodimers. Electrophoretic mobility shift assays revealed that the non-consensus fifth AP-1 binding site (AP-720; nt -720 to -714) had the strongest binding activity for recombinant c-Jun protein, and that the fourth binding site (AP-763; nt -763 to -754) and AP-720 showed strong binding activity for cellular nuclear proteins. Antibody supershift and blocking experiments suggest that AP-720, but not AP-763, binds authentic AP-1 components. Transient transfection reporter assays of deletion constructs showed that the region spanning AP-720 has the highest transcriptional activity, and that sequences 5' to this region (nt -2846 to -747) may contain negative regulatory elements. The deletion construct containing about 500 nt 5' to the transcriptional start, but no AP-1 sites, showed lower but significant activity, suggesting both AP-1-dependent and -independent regulation of the mouse TIMP-3 promoter. Mutational inactivation of AP-720 abolished the activity increment that distinguished the reporter construct containing both AP-720 and sixth AP-1 binding site (AP-617; nt -617 to -611) from that containing only AP-617. In summary, we report here that both AP-1 and non-AP-1 elements contribute to activity, with the non-consensus AP-1 site at -720 showing the greatest functional significance among the AP-1 sites.

3T3 Cells↗

PubMed1997

Expression and characterization of the small subunit of human DNA polymerase delta.

DNA polymerase delta is a heterodimer consisting of a catalytic subunit of 125 kDa and a small subunit of 50 kDa (p50). We have overexpressed p50 in Escherichia coli and have characterized the recombinant protein. p50 was readily overexpressed using the pET vector as an insoluble protein. A procedure was developed for its purification and renaturation. Examination of the physicochemical properties of renatured p50 showed that it is a monomeric protein with an apparent molecular weight of 60,000, a Stokes radius of 34 A, and a sedimentation coefficient of 4.1 S. Its physical properties were indistinguishable from p50 expressed as a soluble protein using the pTACTAC vector. Examination of the effects of recombinant p50 on the activity of DNA polymerase delta showed that p50 is able to slightly stimulate (about 2-fold) the activity of the recombinant 125-kDa catalytic subunit using poly(dA).oligo(dT) as a template in the absence of proliferating cell nuclear antigen. In the presence of proliferating cell nulear antigen, activity is stimulated about 5-fold. Seven stable hybridoma cell lines were established that produced monoclonal antibodies against p50. One of these antibodies (13D5) inhibited the activity of calf thymus DNA polymerase delta. This antibody, when coupled to a solid support, also was found to provide a method for the immunoafffinity purification of recombinant p50 and of DNA polymerase delta from calf thymus or HeLa extracts. Immunoprecipitation and enzyme-linked immunosorbent assays also confirmed that p50 interacts with the catalytic subunit of DNA polymerase delta.

DNA Polymerase III↗

PubMed1997

Induction of glutathione synthetase by 1,10-phenanthroline.

The differential display (DD) was employed to identify the gene(s) responsible for 1,10-phenanthroline (OP)-induced apoptosis in murine tumor cells (Sun, Y., Bian, J., Wang, Y. and Jacobs, C. (1997) Oncogene 14, 385-393 [1]). An OP-inducible gene was isolated which encodes mouse glutathione synthetase (GSS). The GSS mRNA level began to increase 6 h post OP treatment and remained at a high level thereafter up to 24 h tested. Induction of GSS was found not to be associated with p53 activation. No significant induction of DNA fragmentation was detected in two murine tumor lines upon GSS transfection. This is the first observation indicating that GSS is inducible rather specifically by a metal chelator and that induction of GSS, however, is not sufficient to induce apoptosis. It may merely reflect a cellular response to OP-induced redox disturbance.

Animals↗

PubMed1997

An equine herpesvirus-1 gene 71 deletant is attenuated and elicits a protective immune response in mice.

The pathogenesis of pulmonary infection and the immune response following intranasal inoculation of mice with two equine herpesvirus type 1 (EHV-1) deletion mutants have been assessed. The mutants, ED71 and ED75, have deletions in genes 71 (EUS4) and 75 (10K), respectively. Deletions were replaced by the Escherichia coli lacZ gene driven by the simian virus 40 (SV40) early promoter. It has previously been shown that the protein products of genes 71 and 75 are dispensable in vitro but that removal of gene 71 results in a defect in virus maturation and capsid envelopment which impairs the ability of mutant virus to spread via release and readsorption. This study demonstrated that the 192-kDa gene 71 product is required for full expression of virulence in mice, whereas the putative 10-kDa product of gene 75 has minimal effect. Both mutants exhibited the same tissue and cytotropism as wild-type EHV-1 and induced both humoral and cell-mediated immune responses indistinguishable from those induced by the parental strain. Irrespective of the reduced pathogenicity of the gene 71 mutant, infected mice were protected against a challenge with wild-type EHV-1. These findings highlight the potential of ED71 as a vaccine candidate.

Animals↗

PubMed1997

Regulation of neuropeptide expression in sympathetic neurons. Paracrine and retrograde influences.

Sympathetic neurons and other peripheral neurons exhibit a great deal of plasticity in their neuropeptide phenotype in adulthood. In this review, two phenotypes have been described in detail: that of normal sympathetic neurons and that of axotomized neurons. Two factors produced by nonneuronal cells, LIF and NGF, determine which of these phenotypes is expressed. Under normal conditions, the neurons receive NGF primarily, if not exclusively, from the target tissues they innervate. Prior to surgery, the nonneuronal cells within the ganglion and nerve tract express little, if any, LIF. This milieu favors the expression of NPY and suppresses the expression of VIP, galanin, and substance P (Fig. 6). After axotomy, however, this situation is reversed. The neuronal cell bodies are deprived of target-derived NGF and are exposed to LIF both within the ganglion and at the site of the injury (Fig 6). Both the removal of NGF and the exposure to LIF inhibit NPY expression, while promoting the expression of VIP and galanin. Expression of substance P after axotomy occurs primarily, if not entirely, because of the effects of LIF, with the removal of NGF playing no obvious role in the regulation of this peptide.

Animals↗

PubMed1997

The capital-asset-pricing model and arbitrage pricing theory: a unification.

We present a model of a financial market in which naive diversification, based simply on portfolio size and obtained as a consequence of the law of large numbers, is distinguished from efficient diversification, based on mean-variance analysis. This distinction yields a valuation formula involving only the essential risk embodied in an asset's return, where the overall risk can be decomposed into a systematic and an unsystematic part, as in the arbitrage pricing theory; and the systematic component further decomposed into an essential and an inessential part, as in the capital-asset-pricing model. The two theories are thus unified, and their individual asset-pricing formulas shown to be equivalent to the pervasive economic principle of no arbitrage. The factors in the model are endogenously chosen by a procedure analogous to the Karhunen-Loéve expansion of continuous time stochastic processes; it has an optimality property justifying the use of a relatively small number of them to describe the underlying correlational structures. Our idealized limit model is based on a continuum of assets indexed by a hyperfinite Loeb measure space, and it is asymptotically implementable in a setting with a large but finite number of assets. Because the difficulties in the formulation of the law of large numbers with a standard continuum of random variables are well known, the model uncovers some basic phenomena not amenable to classical methods, and whose approximate counterparts are not already, or even readily, apparent in the asymptotic setting.

Journal Article↗

PubMed1997

HIV-1 entry and macrophage inflammatory protein-1beta-mediated signaling are independent functions of the chemokine receptor CCR5.

The human immunodeficiency virus type 1 (HIV-1) requires the presence of specific chemokine receptors in addition to CD4 to enter its target cell. The chemokine receptor CCR5 is used by macrophage-tropic strains of HIV-1, which predominate during the asymptomatic stages of infection. Here we investigate whether the ability of CCR5 to signal in response to its beta-chemokine ligands is necessary or sufficient for viral entry. Three CCR5 mutants with little or no ability to mobilize calcium in response to macrophage inflammatory protein-1beta could nonetheless support HIV-1 entry and the early steps in the virus life cycle with efficiencies comparable with those of wild-type CCR5. Conversely, a chimeric receptor with the N terminus of CCR2 replacing that of CCR5 responded to macrophage inflammatory protein-1beta and MCP-1 but did not efficiently support viral entry. These results demonstrate that chemokine signaling and HIV-1 entry are separable functions of CCR5 and that only viral entry requires the N-terminal domain of CCR5.

Animals↗

PubMed1997

Activation of p53 transcriptional activity by 1,10-phenanthroline, a metal chelator and redox sensitive compound.

p53, a tumor suppressor gene, functioning as a transcription factor, has been recently shown in a cell free system to be subject to redox (reduction/oxidation) regulation. Oxidants or metal chelating reagents disrupt wildtype p53 conformation and decrease or abolish its DNA binding activity, while reductants restore wildtype conformation and increase DNA binding. We have extended these observations to intact cell systems by using luciferase transactivation assay in two murine tumor cell lines, both harboring endogenous wildtype p53. The results showed that none of these in vitro active reagents, except 1,10-phenanthroline (OP) has a significant effect on p53 transactivation activity. OP, a metal chelator and p53 inactivator in cell free systems, however, induces p53 transactivation activity as well as sequence-specific DNA binding in a dose dependent manner. OP also differentially induces endogenous expression of several known p53 target genes such as Waf-1 and Mdm-2, but not Bax, Gadd45, and PCNA. Increased p53 activity induced by OP is not due to elevated p53 mRNA nor to protein levels. Furthermore, the OP-induced p53 transcriptional activation is not due to its potential DNA intercalating activity, but mainly due to its metal chelating activity. OP was also found to induce dramatically apoptotic cell death in these tumor cells harboring wildtype p53, to a less extent in MEF cells from p53 knockout mice and not at all in Saos-2 cells without p53 or Rb. We concluded from this study that (a) unlike what has been seen in vitro, OP induces p53 activity in intact cells (b) OP activates p53 transcriptional activity without increasing p53 protein; and (c) activation of p53 may contribute to apoptosis, but is not required.

Animals↗

PubMed1997

Nuclear import of HIV-1 DNA in resting CD4+ T cells requires a cyclosporin A-sensitive pathway.

Using PCR to monitor early (LTR/LTR (long terminal repeat)) and late (LTR/gag) products of reverse transcription and the formation of HIV-1 LTR circles (indicating nuclear import), we explored the relationship between T cell activation signals and early events in the life cycle of HIV-1 infection. The combination of TCR ligation with either CD28 cross-linking or exogenous IL-2 was required for HIV-1 LTR circle formation in resting CD4+ T cells. Ligation of the TCR or CD28 receptors or addition of IL-2 alone did not induce this process. However, cross-linking the TCR, or IL-2 alone, unlike CD28 ligation, could induce the completion of viral reverse transcription. In contrast, the initiation of HIV-1 reverse transcription could occur in resting CD4+ T cells without any stimulation. Cyclosporin A (CsA), an inhibitor of T cell activation, completely blocked HIV-1 DNA nuclear import in activated CD4+ T cells. The completion of HIV-1 reverse transcription was blocked by CsA in infected CD4+ T cells activated by TCR ligation and IL-2, but not in cells stimulated by TCR and CD28 ligation. The costimulation of CD3 and CD28 mAbs in the presence of IL-2 could not overcome the CsA inhibitory effect on nuclear import of viral DNA. Therefore, the factor(s) involved in a CsA-sensitive pathway plays a critical role in HIV-1 DNA transport from the cytoplasm into the nucleus. Production and movement of HIV-1 DNA in resting CD4+ T cells require two signals: one signal from the TCR, which normally regulates the G0 to G1 transition, induces completion of viral reverse transcription; the other signal through CD28 or an IL-2R-dependent process is sensitive to CsA treatment and regulates viral DNA entry into the nucleus.

Antibodies, Monoclonal↗

PubMed1997

Human prostatic carcinoma oncogene PTI-1 is expressed in human tumor cell lines and prostate carcinoma patient blood samples.

Rapid expression cloning and differential RNA display identifies a gene, named prostate tumor inducing gene-1 (PTI-1), that is differentially expressed in prostate cancer versus normal prostate and benign prostatic hypertrophy. PTI-1 encodes a truncated and mutated human elongation factor 1 alpha, and its 5' untranslated region (UTR) shares significant homology with the 23S rRNA gene of Mycoplasma hyopneumoniae. PCR with human genomic DNAs, using PTI-1 5' UTR-specific primers, suggests that this sequence is part of the human genome. Furthermore, reverse transcription (RT)-PCR, with one primer specific to the 5' UTR region and the other to the elongation factor 1 alpha coding region, amplifies PTI-1 transcripts from total RNA of various human tumor cell lines and blood samples from prostate carcinoma patients. RT-PCR products with the predicted size and sequence of PTI-1 are detected in RNAs from cell lines of human prostate, breast, and colon carcinomas. This RT-PCR product is shown by Southern blotting and sequence analyses to contain the junction sequence between the 5' UTR and the coding region of the PTI-1 gene. Furthermore, RT-PCR analysis indicates that the PTI-1 gene is also expressed in prostate carcinoma patient-derived blood samples. On the basis of serial dilution experiments, PTI-1 can detect 1 prostate carcinoma cell in 10(8) cells not expressing PTI-1. In this context, PTI-1 represents a sensitive marker for detecting human prostate cancer in the bloodstream. This study confirms the authenticity of the PTI-1 gene and documents its potential clinical utility as a sensitive and specific indicator of prostate cancer progression.

Base Sequence↗

PubMed1997

Sensitivity and specificity of left ventricular ejection fraction by echocardiographic automated border detection: comparison with radionuclide ventriculography.

BACKGROUND: Echocardiographic automated border detection (ABD) provides on-line, beat-to-beat estimation of left ventricular (LV) ejection fraction (EF). Sensitivity and specificity of using ABD-EF for diagnosing LV dysfunction in routine clinical situations have not been previously studied. HYPOTHESIS: Analysis of ABD-EF data based on receiver operating characteristic (ROC) should provide useful information about sensitivity and specificity for clinical diagnosis of LV function based on ABD-EF. METHODS: The study group included 50 consecutive patients with EF measured by both ABD and radionuclide ventriculography (RVG). ABD-EF was recorded for 25 consecutive heart beats in the apical four-chamber view. Data were analyzed statistically by linear regression, Bland-Altman plot, and ROC. In ROC analysis, abnormal LV function was defined RVG-EF < or = 40%. RESULTS: ABD and RVG showed a moderate correlation in the EF measurements: slope = 0.93, intercept = 17%, r = 0.79 (n = 50). Interbeat variability in ABD was diminished by averaging consecutive beats; standard error of estimate (SEE) decreased from 15.6% without averaging to 12.5% with 25-beat averaging. Bland-Altman analysis indicated that ABD-EF compared unfavorably with RVG-EF, with limits of agreement from -11% to 39%. ABD-EF showed a systematic overestimation (p < 0.005), which was compensated by increasing the threshold for abnormal ABD-EF to 56%. With the optimized threshold, ABD-EF provided 89% sensitivity and 89% specificity (85% overall diagnostic accuracy) for diagnosing abnormal LV function. CONCLUSION: This study explored the limitations of on-line echocardiographic measurement of EF in a clinical setting and provided useful data for assessing interbeat variability, sensitivity, and specificity.

Aged↗

PubMed1997

TIMP-3 induces cell death by stabilizing TNF-alpha receptors on the surface of human colon carcinoma cells.

Matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) regulate the structural integrity of the extracellular matrix (ECM). Constitutive expression of human TIMP-3 in human DLD colon carcinoma cells renewed serum-responses and inhibited tumour formation in nude mice. To elucidate the mechanism of TIMP-3-mediated tumour suppression, we compared parental DLD and TIMP-3 expressing DLD cells (TIMP-3/DLD), finding them to be significantly different. TIMP-3/DLD cultures have fewer mitotic cells, are delayed in G1, and die after serum starvation. TIMP-3/DLD conditioned media activates cell death on fibroblast cells. The cell death induced by serum starvation and conditioned media was inhibited by 70%, in the presence of neutralizing tumour necrosis factor alpha (TNF-alpha) antibody. TIMP-3/DLD whole cell lysate contained p55 TNF-alpha receptor, while vector/DLD lysate had p55 TNF-alpha receptor and p46 soluble TNF-alpha inhibitor. Vector/DLD conditioned media had p46, while no soluble TNF-alpha receptor was detected in TIMP-3/DLD conditioned media. In addition, FACS analysis revealed that TIMP-3/DLD cells have more TNF-alpha surface binding sites, suggesting a direct correlation between TIMP-3 expression and surface receptors. The mechanism of tumorigenic reversion induced by TIMP-3 in DLD cells may involve protection of receptors from the proteolytic activity of MMPs. Putative TIMP-3-mediated inhibition of MMPs restores the TNF-alpha p55 signalling pathway and the carcinoma cell is killed by autocrine TNF-alpha. Thus, DLD cells have specific ECM MMPs that cleave cytokines and cytokine receptors. TIMP-3 specifically inhibits MMPs involved in receptor shedding.

Antigens, CD↗

PubMed1997

Fibrous tissue and angiotensin II.

Myofibroblasts (myoFb) are cells responsible for fibrous tissue formation in injured systemic organs such as the heart. Cultured myoFb, obtained from rat cardiac scar tissue, express genes that encode components requisite for angiotensin (Ang) II generation, which in turn regulates myoFb collagen turnover in an autocrine/paracrine manner. In this study, we tested the hypothesis that these wound-healing fibroblast-like cells and locally generated Ang II are involved in other repairing tissue. To test this hypothesis, we used a granuloma pouch model, where a subcutaneous air sac is created followed by injection of croton oil. Pouch tissue was collected at days 4, 7, 14 and 21. The presence of myoFb was determined by immunohistochemical alpha-smooth muscle actin (alpha-SMA) labeling and collagen accumulation by picrosirius red staining. Angiotensin converting enzyme (ACE) and Ang II receptor binding were detected by in vitro quantitative autoradiography using 125I-351A and 125I[Sar1, Ile8]Ang II, respectively, while Ang II receptor subtype was defined by displacement studies using either an AT1 (losartan) or AT2 (PD123177) receptor antagonist. Cells expressing ACE were determined by immunohistochemistry. Ang II content in pouch tissue was measured by radioimmunoassay following HPLC separation while its capacity to generate Ang II was assessed in tissue bath, with and without exogenous Ang I or lisinopril, an ACE inhibitor. Collagen accumulation in pouch tissue was examined by determining hydroxyproline content in response to lisinopril, AT1 or AT2 receptor antagonists (losartan or PD123177). In pouch tissue, we found: (1) myoFb at day 4 which became more extensive at days 7, 14 and 21; (2) morphologic evidence of collagen deposition evident at day 4, which gradually became more extensive thereafter; (3) ACE and Ang II receptor binding was evident at day 4 and remained invariant on days 7, 14 and 21; (4) the predominant Ang II receptor subtype expressed was AT1; (5) myoFb express ACE and AT1 receptors; (6) picogram quantities of Ang II (per g tissue) was evident on days 7, 14 and 21; and (7) Ang II was generated from Ang I substrate. Lisinopril and losartan, but not PD123177, significantly attenuated pouch weight and accumulation of collagen. Thus, in this model of cutaneous repair, the appearance of myoFb is associated with Ang II generation that regulates fibrogenesis by AT1 receptor binding. Signals involved in the appearance of myoFb remain uncertain. Further studies are required to address the regulation of Ang II generation in pouch tissue of the rat.

Actins↗

PubMed1997

Local angiotensin II and myocardial fibrosis.

Tissue repair appears in the infarcted heart at both infarcted and noninfarcted myocardium. Experimental evidence gathered to date indicates that myoFb are the predominant cell responsible for collagen formation at sites of repair in the rat heart and related structures. These phenotypically transformed fibroblast-like cells are not normal residents of ventricular tissue. They appear on day 4 at sites of injury and remain abundant for weeks therefore. MyoFb express type I collagen mRNA and ACE and AT1 receptors. ACE inhibitors or AT1 receptor antagonists attenuate collagen accumulation in both infarcted and noninfarcted myocardium. These findings suggest locally generated AngII may have an autocrine function in regulating myoFb collagen turnover.

Angiotensin II↗