GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Ovid Technologies (Wolters Kluwer Health)  (34)
  • 1
    Online Resource
    Online Resource
    Theranostical nanosystem‐mediated identification of an oncogene and highly effective therapy in hepatocellular carcinoma
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Hepatology Vol. 63, No. 4 ( 2016-04), p. 1240-1255
    Details
    In: Hepatology, Ovid Technologies (Wolters Kluwer Health), Vol. 63, No. 4 ( 2016-04), p. 1240-1255
    Abstract: Because the primary surgical treatment options for hepatocellular carcinoma (HCC)—including hepatic resection and liver transplantation—often fail due to recurrence and metastasis, identifying early prognostic biomarkers and therapeutic targets for HCC is of great importance. This study shows that transducin β‐like protein 1–related protein (TBLR1) is a key HCC oncogene that plays important roles in HCC proliferation, antiapoptosis, and angiogenesis by regulating the Wnt/β‐catenin pathway. The folate‐targeted theranostic small interfering RNA (siRNA) nanomedicine Fa‐PEG ‐g‐ PEI‐SPION/ p siRNA‐TBLR1 effectively silences the TBLR1 gene in different human HCC cell lines in vitro and in human HCC samples in vivo , resulting in the simultaneous suppression of HCC cell proliferation, antiapoptosis, and angiogenesis. Because of its multi‐anticancer functions against HCC, intravenous injection of the folate‐targeted siRNA nanomedicine into nude mice bearing intrahepatic or subcutaneous xenografts of human HCC has a significant therapeutic effect. Tumor growth in those animals was almost completely inhibited by treatment with Fa‐PEG ‐g‐ PEI‐SPION/ p siRNA‐TBLR1. Moreover, the SPION‐encapsulated polyplexes possess high magnetic resonance imaging (MRI) detection sensitivity, which makes tumor‐targeted siRNA delivery easily trackable using the clinical MRI technique. Conclusion : The theranostic siRNA nanomedicine examined here possesses great theranostic potential for combined gene therapy and MRI diagnosis of HCC. (H epatology 2016;63:1240–1255)
    Type of Medium: Online Resource
    ISSN: 0270-9139 , 1527-3350
    URL: Article
    DOI: 10.1002/hep.28409
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 1472120-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Genetic Deficiency of Glutathione S -Transferase P Increases Myocardial Sensitivity to Ischemia–Reperfusion Injury
    Ovid Technologies (Wolters Kluwer Health) ; 2015
    In:  Circulation Research Vol. 117, No. 5 ( 2015-08-14), p. 437-449
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 117, No. 5 ( 2015-08-14), p. 437-449
    Abstract: Myocardial ischemia–reperfusion (I/R) results in the generation of oxygen-derived free radicals and the accumulation of lipid peroxidation–derived unsaturated aldehydes. However, the contribution of aldehydes to myocardial I/R injury has not been assessed. Objective: We tested the hypothesis that removal of aldehydes by glutathione S -transferase P (GSTP) diminishes I/R injury. Methods and Results: In adult male C57BL/6 mouse hearts, Gstp1/2 was the most abundant GST transcript followed by Gsta4 and Gstm4.1 , and GSTP activity was a significant fraction of the total GST activity. mGstp1/2 deletion reduced total GST activity, but no compensatory increase in GSTA and GSTM or major antioxidant enzymes was observed. Genetic deficiency of GSTP did not alter cardiac function, but in comparison with hearts from wild-type mice, the hearts isolated from GSTP-null mice were more sensitive to I/R injury. Disruption of the GSTP gene also increased infarct size after coronary occlusion in situ. Ischemia significantly increased acrolein in hearts, and GSTP deficiency induced significant deficits in the metabolism of the unsaturated aldehyde, acrolein, but not in the metabolism of 4-hydroxy- trans -2-nonenal or trans -2-hexanal; on ischemia, the GSTP-null hearts accumulated more acrolein-modified proteins than wild-type hearts. GSTP deficiency did not affect I/R-induced free radical generation, c-Jun N-terminal kinase activation, or depletion of reduced glutathione. Acrolein exposure induced a hyperpolarizing shift in I Na , and acrolein-induced cell death was delayed by SN-6, a Na + /Ca ++ exchange inhibitor. Cardiomyocytes isolated from GSTP-null hearts were more sensitive than wild-type myocytes to acrolein-induced protein crosslinking and cell death. Conclusions: GSTP protects the heart from I/R injury by facilitating the detoxification of cytotoxic aldehydes, such as acrolein.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/CIRCRESAHA.114.305518
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
    detail.hit.zdb_id: 1467838-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Cardiospecific Overexpression of ATPGD1 (Carnosine Synthase) Increases Histidine Dipeptide Levels and Prevents Myocardial Ischemia Reperfusion Injury
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Journal of the American Heart Association Vol. 9, No. 12 ( 2020-06-16)
    Details
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 9, No. 12 ( 2020-06-16)
    Abstract: Myocardial ischemia reperfusion (I/R) injury is associated with complex pathophysiological changes characterized by pH imbalance, the accumulation of lipid peroxidation products acrolein and 4‐hydroxy trans ‐2‐nonenal, and the depletion of ATP levels. Cardioprotective interventions, designed to address individual mediators of I/R injury, have shown limited efficacy. The recently identified enzyme ATPGD1 (Carnosine Synthase), which synthesizes histidyl dipeptides such as carnosine, has the potential to counteract multiple effectors of I/R injury by buffering intracellular pH and quenching lipid peroxidation products and may protect against I/R injury . METHODS AND RESULTS We report here that β‐alanine and carnosine feeding enhanced myocardial carnosine levels and protected the heart against I/R injury. Cardiospecific overexpression of ATPGD 1 increased myocardial histidyl dipeptides levels and protected the heart from I/R injury. Isolated cardiac myocytes from ATPGD 1‐transgenic hearts were protected against hypoxia reoxygenation injury. The overexpression of ATPGD 1 prevented the accumulation of acrolein and 4‐hydroxy trans ‐2‐nonenal–protein adducts in ischemic hearts and delayed acrolein or 4‐hydroxy trans ‐2‐nonenal–induced hypercontracture in isolated cardiac myocytes. Changes in the levels of ATP , high‐energy phosphates, intracellular pH, and glycolysis during low‐flow ischemia in the wild‐type mice hearts were attenuated in the ATPGD 1‐transgenic hearts. Two natural dipeptide analogs (anserine and balenine) that can either quench aldehydes or buffer intracellular pH , but not both, failed to protect against I/R injury. CONCLUSIONS Either exogenous administration or enhanced endogenous formation of histidyl dipeptides prevents I/R injury by attenuating changes in intracellular pH and preventing the accumulation of lipid peroxidation derived aldehydes.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    URL: Article
    DOI: 10.1161/JAHA.119.015222
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 2653953-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Abstract 11928: Cardiospecific Overexpression of Carnosine Synthase Attenuates Myocardial Ischemia Reperfusion Injury
    Ovid Technologies (Wolters Kluwer Health) ; 2014
    In:  Circulation Vol. 130, No. suppl_2 ( 2014-11-25)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 130, No. suppl_2 ( 2014-11-25)
    Abstract: Even though myocardial ischemia/reperfusion (I/R) remains the leading cause of death, the underlying mechanisms remain incompletely understood. Increased formation of reactive carbonyl has been shown to be a common biochemical feature of I/R injury. These carbonyls are generated from the oxidation of proteins and membrane lipids. Reactive carbonyls such as methylglyoxal are generated from increased glycolytic activity during ischemia. Previous work in our lab has shown that the endogenous dipeptide carnosine (β-alanine-histidine) quenches both protein and lipid derived carbonyls. It can also buffer changes in intracellular pH and chelate metals that catalyze ROS production. In the heart, carnosine is synthesized by the ATP grasp enzyme (ATPGD1). Hence, we examined whether overexpression of ATPGD1 could increase carnosine synthesis in the heart and attenuate I/R injury. To overexpress ATPGD1, we generated mice in which the expression of the transgene was driven by cardiospecific α-MHC promoter. Two different ATPGD1Tg mouse lines were generated, which showed 10-15 fold higher abundance of ATPGD1 protein in the heart compared with their wild-type (WT) littermates. Cardiac levels of the histidyl dipeptides anserine and carnosine were approximately 100 fold higher in the ATPGD1Tg than WT mice hearts (WT: anserine 1.8±0.3 pmoles/mg protein, carnosine 6±1 pmoles/mg protein; ATPGD1-Tg: anserine 114±15 pmoles/mg protein, carnosine 615±44 pmoles/mg protein). No changes in the levels of these dipeptides were observed in other tissues of the ATPGD1Tg mice. Echocardiographic analysis showed that ATPGD1 overexpression did not affect cardiac function. When subjected to 30 min of coronary occlusion followed by 24 h of reperfusion, the infarct size was significantly lower in ATPGD1Tg than WT mice. Infarct size as the area of risk of left ventricle was 59±3.02% in WT mice and 38±2.73% in the ATPGD1-Tg mice (p 〈 0.05 vs WT; n=7-8), indicating that increasing carnosine levels attenuates myocardial I/R injury. These findings reveal a novel cardioprotective role of endogenous histidyl dipeptides in decreasing I/R injury and suggest that treatment with such peptides may be a potential therapy for decreasing myocardial I/R injury and its progression of heart failure.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.130.suppl_2.11928
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2014
    detail.hit.zdb_id: 1466401-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Abstract 213: The Late Phase of Ischemic Preconditioning Is Abrogated by a Specific Prostaglandin I2 Receptor Antagonist
    Ovid Technologies (Wolters Kluwer Health) ; 2007
    In:  Circulation Vol. 116, No. suppl_16 ( 2007-10-16)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 116, No. suppl_16 ( 2007-10-16)
    Abstract: Previous studies have shown that cyclooxygenase-2 (COX-2) mediates the late phase of ischemic preconditioning (PC) by producing various cardioprotective prostanoids including prostacyclin (PGI 2 ) and prostaglandin (PG) E 2 (PGE 2 ). Prostanoids are known to act via activation of specific receptors. However, the specific PG receptors responsible for the salubrious actions of COX-2 in PC and myocardial ischemia/reperfusion injury remain unclear. The PGI 2 receptor (IP) mediates the actions of PGI 2 and PGE 2 , the two major COX-2-derived prostanoids with cardioprotective properties. Accordingly, the goal of this study was to determine the role of the IP in late PC. C57BL/6 mice underwent a 30-min coronary occlusion (O) followed by 24 h of reperfusion (R). Administration of the IP receptor selective antagonist, RO 3244794 (group III, 10 mg/kg i.p.), 30 min prior to the 30-min O had no appreciable effect on infarct size compared with untreated and vehicle-treated groups (68.4 ± 1.2 % vs. 63.3 ± 3.1 % and 65.6 ± 3.9 % of the risk region, respectively). When mice were preconditioned with six cycles of 4-min O/4-min R 24 h prior to the 30-min O, infarct size was markedly reduced (group IV, 33.2 ± 2.9 %), indicating a late PC effect. In the vehicle-treated late PC group, infarct size (group V, 37.2 ± 4.9 %) was similar to the late PC group, indicating the vehicle had no effect. However, the protective effect of late PC was completely abrogated by administration of RO 3244794 30 min before the 30-min O (group VI, 63.8 ± 4.5 %). We conclude that the IP receptor is an obligatory mediator of the late phase of ischemic PC in vivo , suggesting that pharmacologic manipulations of this receptor may be therapeutically useful.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.116.suppl_16.II_21-d
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2007
    detail.hit.zdb_id: 1466401-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Gene Dosage-Dependent Effects of Cardiac-Specific Overexpression of the A 3 Adenosine Receptor
    Ovid Technologies (Wolters Kluwer Health) ; 2002
    In:  Circulation Research Vol. 91, No. 2 ( 2002-07-26), p. 165-172
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 91, No. 2 ( 2002-07-26), p. 165-172
    Abstract: We used a genetic approach to determine whether increasing the level of A 3 adenosine receptors (A 3 ARs) expressed in the heart confers protection against ischemia without causing cardiac pathology. We generated mice carrying one (A 3 tg.1) or six (A 3 tg.6) copies of a transgene consisting of the cardiomyocyte-specific α-myosin heavy chain gene promoter and the A 3 AR cDNA. A 3 tg.1 and A 3 tg.6 mice expressed 12.7±3.15 and 66.3±9.4 fmol/mg of the high-affinity G protein–coupled form of the A 3 AR in the myocardium, respectively. Extensive morphological, histological, and functional analyses demonstrated that there were no apparent abnormalities in A 3 tg.1 transgenic mice compared with nontransgenic mice. In contrast, A 3 tg.6 mice exhibited dilated hearts, expression of markers of hypertrophy, bradycardia, hypotension, and systolic dysfunction. When A 3 tg mice were subjected to 30 minutes of coronary occlusion and 24 hours of reperfusion, infarct size was reduced ≈30% in A 3 tg.1 mice and ≈40% in A 3 tg.6 mice compared with nontransgenic littermates. The reduction in infarct size in the transgenic mice was not related to differences in risk region size, systemic hemodynamics, or body temperature, indicating that the cardioprotection was a result of increased A 3 AR signaling in the ischemic myocardium. The results demonstrate that low-level expression of A 3 ARs in the heart provides effective protection against ischemic injury without detectable adverse effects, whereas higher levels of A 3 AR expression lead to the development of a dilated cardiomyopathy.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/01.RES.0000028007.91385.EE
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2002
    detail.hit.zdb_id: 1467838-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Transient Cell Cycle Induction in Cardiomyocytes to Treat Subacute Ischemic Heart Failure
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Circulation Vol. 145, No. 17 ( 2022-04-26), p. 1339-1355
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 145, No. 17 ( 2022-04-26), p. 1339-1355
    Abstract: The regenerative capacity of the heart after myocardial infarction is limited. Our previous study showed that ectopic introduction of 4 cell cycle factors (4F; CDK1 [cyclin-dependent kinase 1], CDK4 [cyclin-dependent kinase 4] , CCNB [cyclin B1], and CCND [cyclin D1] ) promotes cardiomyocyte proliferation in 15% to 20% of infected cardiomyocytes in vitro and in vivo and improves cardiac function after myocardial infarction in mice. Methods: Using temporal single-cell RNA sequencing, we aimed to identify the necessary reprogramming stages during the forced cardiomyocyte proliferation with 4F on a single cell basis. Using rat and pig models of ischemic heart failure, we aimed to start the first preclinical testing to introduce 4F gene therapy as a candidate for the treatment of ischemia-induced heart failure. Results: Temporal bulk and single-cell RNA sequencing and further biochemical validations of mature human induced pluripotent stem cell–derived cardiomyocytes treated with either LacZ or 4F adenoviruses revealed full cell cycle reprogramming in 15% of the cardiomyocyte population at 48 hours after infection with 4F, which was associated mainly with sarcomere disassembly and metabolic reprogramming (n=3/time point/group). Transient overexpression of 4F, specifically in cardiomyocytes, was achieved using a polycistronic nonintegrating lentivirus (NIL) encoding 4F; each is driven by a TNNT2 (cardiac troponin T isoform 2) promoter (TNNT2-4Fpolycistronic-NIL). TNNT2-4Fpolycistronic-NIL or control virus was injected intramyocardially 1 week after myocardial infarction in rats (n=10/group) or pigs (n=6–7/group). Four weeks after injection, TNNT2-4Fpolycistronic-NIL–treated animals showed significant improvement in left ventricular ejection fraction and scar size compared with the control virus–treated animals. At 4 months after treatment, rats that received TNNT2-4Fpolycistronic-NIL still showed a sustained improvement in cardiac function and no obvious development of cardiac arrhythmias or systemic tumorigenesis (n=10/group). Conclusions: This study provides mechanistic insights into the process of forced cardiomyocyte proliferation and advances the clinical feasibility of this approach by minimizing the oncogenic potential of the cell cycle factors owing to the use of a novel transient and cardiomyocyte-specific viral construct.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.121.057641
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1466401-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    The NHLBI-Sponsored Consortium for preclinicAl assESsment of cARdioprotective Therapies (CAESAR) : A New Paradigm for Rigorous, Accurate, and Reproducible Evaluation of Putative Infarct-Sparing Interventions in Mice, Rabbits, and Pigs
    Ovid Technologies (Wolters Kluwer Health) ; 2015
    In:  Circulation Research Vol. 116, No. 4 ( 2015-02-13), p. 572-586
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 116, No. 4 ( 2015-02-13), p. 572-586
    Abstract: Despite 4 decades of intense effort and substantial financial investment, the cardioprotection field has failed to deliver a single drug that effectively reduces myocardial infarct size in patients. A major reason is insufficient rigor and reproducibility in preclinical studies. Objective: To develop a multicenter, randomized, controlled, clinical trial-like infrastructure to conduct rigorous and reproducible preclinical evaluation of cardioprotective therapies. Methods and Results: With support from the National Heart, Lung, and Blood Institute, we established the Consortium for preclinicAl assESsment of cARdioprotective therapies (CAESAR), based on the principles of randomization, investigator blinding, a priori sample size determination and exclusion criteria, appropriate statistical analyses, and assessment of reproducibility. To validate CAESAR, we tested the ability of ischemic preconditioning to reduce infarct size in 3 species (at 2 sites/species): mice (n=22–25 per group), rabbits (n=11–12 per group), and pigs (n=13 per group). During this validation phase, (1) we established protocols that gave similar results between centers and confirmed that ischemic preconditioning significantly reduced infarct size in all species and (2) we successfully established a multicenter structure to support CAESAR’s operations, including 2 surgical centers for each species, a Pathology Core (to assess infarct size), a Biomarker Core (to measure plasma cardiac troponin levels), and a Data Coordinating Center—all with the oversight of an external Protocol Review and Monitoring Committee. Conclusions: CAESAR is operational, generates reproducible results, can detect cardioprotection, and provides a mechanism for assessing potential infarct-sparing therapies with a level of rigor analogous to multicenter, randomized, controlled clinical trials. This is a revolutionary new approach to cardioprotection. Importantly, we provide state-of-the-art, detailed protocols (“CAESAR protocols”) for measuring infarct size in mice, rabbits, and pigs in a manner that is rigorous, accurate, and reproducible.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/CIRCRESAHA.116.305462
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
    detail.hit.zdb_id: 1467838-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    Abstract 1614: Inducible Nitric Oxide Synthase Upregulates Heme Oxygenase-1 (HO-1) in Myocardium by Enhancing Nrf2 Phosphorylation and Binding to the HO-1 Promoter
    Ovid Technologies (Wolters Kluwer Health) ; 2008
    In:  Circulation Vol. 118, No. suppl_18 ( 2008-10-28)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 118, No. suppl_18 ( 2008-10-28)
    Abstract: Previous studies have shown that iNOS gene transfer leads to elevated expression of HO-1, which in turn protects against ischemic injury. However, the mechanism of this effect is unknown. Recently, Nrf2 has emerged as a key transcription factor in response to stress. Thus, we hypothesized that the upregulation of HO-1 by iNOS gene therapy involves an Nrf2-mediated pathway. Mice received injections in anterior LV wall of Av3/LacZ or Av3/iNOS; 3 days later, they were subjected to a 30-min coronary occlusion and 4 h of reperfusion. At 24 h after iNOS gene transfer (confirmed by iNOS immunoblotting), phosphorylated Nrf2 increased significantly in the myocardial nuclear fraction (+ 220% vs. LacZ group, n=6, P 〈 0.05; Fig ); chromatin Nrf2-immunoprecipitation (Nrf2-ChIP) analysis in vivo showed that Nrf2 was specifically recruited to the HO-1 gene promoter (+ 4.7-fold vs. LacZ group, n=4, P 〈 0.05; Fig ). At 3 days after iNOS gene transfer, myocardial HO-1 protein expression increased markedly (+ 2.6-fold vs. LacZ group, n=6, P 〈 0.05; Fig ), but HO-2 did not change (n=3). The infarct-sparing effects of iNOS gene therapy were completely abrogated by disruption of Nrf2 (Nrf2−/−) (62.8±2.1% in Nrf2−/−+Av3/iNOS group, n=5, vs. 15.3±4.3% in WT+Av3/iNOS group, n=7; Fig ). We conclude that iNOS upregulates HO-1 by enhancing Nrf2 phosphorylation and binding to the HO-1 promoter; and targeted disruption of the Nrf2 gene completely abrogates cardioprotection after iNOS gene transfer. These results provide unequivocal molecular genetic evidence for a necessary role of Nrf2 in the protection afforded by iNOS. Thus, activation of Nrf2 is a key molecular event that links iNOS to HO-1.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.118.suppl_18.S_358
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2008
    detail.hit.zdb_id: 1466401-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    Postinfarct Cytokine Therapy Regenerates Cardiac Tissue and Improves Left Ventricular Function
    Ovid Technologies (Wolters Kluwer Health) ; 2006
    In:  Circulation Research Vol. 98, No. 8 ( 2006-04-28), p. 1098-1105
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 98, No. 8 ( 2006-04-28), p. 1098-1105
    Abstract: We systematically investigated the comparative efficacy of three different cytokine regimens, administered after a reperfused myocardial infarction, in regenerating cardiac tissue and improving left ventricular (LV) function. Wild-type (WT) mice underwent a 30-minute coronary occlusion followed by reperfusion and received vehicle, granulocyte colony-stimulating factor (G-CSF)+Flt-3 ligand (FL), G-CSF+stem cell factor (SCF), or G-CSF alone starting 4 hours after reperfusion. In separate experiments, chimeric mice generated by reconstitution of radioablated WT mice with bone marrow from enhanced green fluorescent protein (EGFP) transgenic mice underwent identical protocols. Mice were euthanized 5 weeks later. Echocardiographically, LV function was improved in G-CSF+FL– and G-CSF+SCF–treated but not in G-CSF–treated mice, whereas LV end-diastolic dimensions were smaller in all three groups. Morphometrically, cytokine-treated hearts had smaller LV diameter and volume. Numerous EGFP-positive cardiomyocytes, capillaries, and arterioles were noted in the infarcted region in cytokine-treated chimeric mice treated with G-CSF+FL or G-CSF+SCF, but the numbers were much smaller in G-CSF–treated mice. G-CSF+FL therapy mobilized bone marrow–derived cells exhibiting increased expression of surface antigens (CD62L and CD11a) that facilitate homing. We conclude that postinfarct cytokine therapy with G-CSF+FL or G-CSF+SCF limits adverse LV remodeling and improves LV performance by promoting cardiac regeneration and probably also by exerting other beneficial actions unrelated to regeneration, and that G-CSF alone is less effective .
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/01.RES.0000218454.76784.66
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2006
    detail.hit.zdb_id: 1467838-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...