34 results on '"Zaccagnini, Germana"'
Search Results
2. Hypoxia-induced miR-210 modulates the inflammatory response and fibrosis upon acute ischemia
- Author
-
Zaccagnini Germana, Greco Simona, Longo Marialucia, Maimone Biagina, Voellenkle Christine, Fuschi Paola, Carrara Matteo, Creo Pasquale, Maselli Davide, Tirone Mario, Mazzone Massimiliano, Gaetano Carlo, Spinetti Gaia, and Martelli Fabio
- Subjects
Cytology ,QH573-671 - Abstract
Abstract Hypoxia-induced miR-210 is a crucial component of the tissue response to ischemia, stimulating angiogenesis and improving tissue regeneration. Previous analysis of miR-210 impact on the transcriptome in a mouse model of hindlimb ischemia showed that miR-210 regulated not only vascular regeneration functions, but also inflammation. To investigate this event, doxycycline-inducible miR-210 transgenic mice (Tg-210) and anti-miR-210 LNA-oligonucleotides were used. It was found that global miR-210 expression decreased inflammatory cells density and macrophages accumulation in the ischemic tissue. To dissect the underpinning cell mechanisms, Tg-210 mice were used in bone marrow (BM) transplantation experiments and chimeric mice underwent hindlimb ischemia. MiR-210 overexpression in the ischemic tissue was sufficient to increase capillary density and tissue repair, and to reduce inflammation in the presence of Wt-BM infiltrating cells. Conversely, when Tg-210-BM cells migrated in a Wt ischemic tissue, dysfunctional angiogenesis, inflammation, and impaired tissue repair, accompanied by fibrosis were observed. The fibrotic regions were positive for α-SMA, Vimentin, and Collagen V fibrotic markers and for phospho-Smad3, highlighting the activation of TGF-β1 pathway. Identification of Tg-210 cells by in situ hybridization showed that BM-derived cells contributed directly to fibrotic areas, where macrophages co-expressing fibrotic markers were observed. Cell cultures of Tg-210 BM-derived macrophages exhibited a pro-fibrotic phenotype and were enriched with myofibroblast-like cells, which expressed canonical fibrosis markers. Interestingly, inhibitors of TGF-β type-1-receptor completely abrogated this pro-fibrotic phenotype. In conclusion, a context-dependent regulation by miR-210 of the inflammatory response was identified. miR-210 expression in infiltrating macrophages is associated to improved angiogenesis and tissue repair when the ischemic recipient tissue also expresses high levels of miR-210. Conversely, when infiltrating an ischemic tissue with mismatched miR-210 levels, macrophages expressing high miR-210 levels display a pro-fibrotic phenotype, leading to impaired tissue repair, fibrosis, and dysfunctional angiogenesis.
- Published
- 2021
- Full Text
- View/download PDF
3. Correction: Hypoxia-induced miR-210 modulates the inflammatory response and fibrosis upon acute ischemia
- Author
-
Zaccagnini, Germana, Greco, Simona, Longo, Marialucia, Maimone, Biagina, Voellenkle, Christine, Fuschi, Paola, Carrara, Matteo, Creo, Pasquale, Maselli, Davide, Tirone, Mario, Mazzone, Massimiliano, Gaetano, Carlo, Spinetti, Gaia, and Martelli, Fabio
- Published
- 2021
- Full Text
- View/download PDF
4. Stable Oxidative Cytosine Modifications Accumulate in Cardiac Mesenchymal Cells From Type2 Diabetes Patients: Rescue by α-Ketoglutarate and TET-TDG Functional Reactivation
- Author
-
Spallotta, Francesco, Cencioni, Chiara, Atlante, Sandra, Garella, Davide, Cocco, Mattia, Mori, Mattia, Mastrocola, Raffaella, Kuenne, Carsten, Guenther, Stefan, Nanni, Simona, Azzimato, Valerio, Zukunft, Sven, Kornberger, Angela, Sürün, Duran, Schnütgen, Frank, von Melchner, Harald, Di Stilo, Antonella, Aragno, Manuela, Braspenning, Maarten, van Criekinge, Wim, De Blasio, Miles J., Ritchie, Rebecca H., Zaccagnini, Germana, Martelli, Fabio, Farsetti, Antonella, Fleming, Ingrid, Braun, Thomas, Beiras-Fernandez, Andres, Botta, Bruno, Collino, Massimo, Bertinaria, Massimo, Zeiher, Andreas M., and Gaetano, Carlo
- Published
- 2018
- Full Text
- View/download PDF
5. Reduction of Cardiac Fibrosis by Interference With YAP-Dependent Transactivation
- Author
-
Garoffolo, Gloria, primary, Casaburo, Manuel, additional, Amadeo, Francesco, additional, Salvi, Massimo, additional, Bernava, Giacomo, additional, Piacentini, Luca, additional, Chimenti, Isotta, additional, Zaccagnini, Germana, additional, Milcovich, Gesmi, additional, Zuccolo, Estella, additional, Agrifoglio, Marco, additional, Ragazzini, Sara, additional, Baasansuren, Otgon, additional, Cozzolino, Claudia, additional, Chiesa, Mattia, additional, Ferrari, Silvia, additional, Carbonaro, Dario, additional, Santoro, Rosaria, additional, Manzoni, Martina, additional, Casalis, Loredana, additional, Raucci, Angela, additional, Molinari, Filippo, additional, Menicanti, Lorenzo, additional, Pagano, Francesca, additional, Ohashi, Toshiro, additional, Martelli, Fabio, additional, Massai, Diana, additional, Colombo, Gualtiero I., additional, Messina, Elisa, additional, Morbiducci, Umberto, additional, and Pesce, Maurizio, additional
- Published
- 2022
- Full Text
- View/download PDF
6. Increased BACE1-AS long noncoding RNA and β-amyloid levels in heart failure
- Author
-
Greco, Simona, Zaccagnini, Germana, Fuschi, Paola, Voellenkle, Christine, Carrara, Matteo, Sadeghi, Iman, Bearzi, Claudia, Maimone, Biagina, Castelvecchio, Serenella, Stellos, Konstantinos, Gaetano, Carlo, Menicanti, Lorenzo, and Martelli, Fabio
- Published
- 2017
- Full Text
- View/download PDF
7. HDAC2 Blockade by Nitric Oxide and Histone Deacetylase Inhibitors Reveals a Common Target in Duchenne Muscular Dystrophy Treatment
- Author
-
Colussi, Claudia, Mozzetta, Chiara, Gurtner, Aymone, Illi, Barbara, Rosati, Jessica, Straino, Stefania, Ragone, Gianluca, Pescatori, Mario, Zaccagnini, Germana, Antonini, Annalisa, Minetti, Giulia, Martelli, Fabio, Piaggio, Giulia, Gallinari, Paola, Steinkuhler, Christian, Clementi, Emilio, Dell'Aversana, Carmela, Altucci, Lucia, Mai, Antonello, Capogrossi, Maurizio C., Puri, Pier Lorenzo, and Gaetano, Carlo
- Published
- 2008
- Full Text
- View/download PDF
8. Hypoxia-Induced miR-210 Is Necessary for Vascular Regeneration upon Acute Limb Ischemia
- Author
-
Zaccagnini, Germana, primary, Maimone, Biagina, additional, Fuschi, Paola, additional, Longo, Marialucia, additional, Da Silva, Daniel, additional, Carrara, Matteo, additional, Voellenkle, Christine, additional, Perani, Laura, additional, Esposito, Antonio, additional, Gaetano, Carlo, additional, and Martelli, Fabio, additional
- Published
- 2019
- Full Text
- View/download PDF
9. GMP-based CD133+ cells isolation maintains progenitor angiogenic properties and enhances standardization in cardiovascular cell therapy
- Author
-
Gaipa, Giuseppe, Tilenni, Manuela, Straino, Stefania, Burba, Ilaria, Zaccagnini, Germana, Belotti, Daniela, Biagi, Ettore, Valentini, Marco, Perseghin, Paolo, Parma, Matteo, Campli, Cristiana Di, Biondi, Andrea, Capogrossi, Maurizio C., Pompilio, Giulio, and Pesce, Maurizio
- Published
- 2010
- Full Text
- View/download PDF
10. p66ShcA modulates oxidative stress and survival of endothelial progenitor cells in response to high glucose
- Author
-
Stefano, Valeria Di, Cencioni, Chiara, Zaccagnini, Germana, Magenta, Alessandra, Capogrossi, Maurizio C., and Martelli, Fabio
- Published
- 2009
11. Reverse Transcriptase Activity in Mature Spermatozoa of Mouse
- Author
-
Giordano, Roberto, Magnano, Anna Rosa, Zaccagnini, Germana, Pittoggi, Carmine, Moscufo, Nicola, Lorenzini, Rodolfo, and Spadafora, Corrado
- Published
- 2000
12. Implication of long noncoding RNAs in the endothelial cell response to hypoxia revealed by RNA-sequencing
- Author
-
Voellenkle, Christine, Garcia-Manteiga, Jose Manuel, Pedrott, Simona, De Toma, Ilario, Da Silva, Daniel, Maimone, Biagina, Greco, Simona, Fasanaro, Pasquale, Creo, Pasquale, Zaccagnini, Germana, Gaetano, Carlo, and Martelli, Fabio
- Subjects
embryonic structures ,ddc:610 - Abstract
Long noncoding RNAs (lncRNAs) are non-protein coding RNAs regulating gene expression. Although for some lncRNAs a relevant role in hypoxic endothelium has been shown, the regulation and function of lncRNAs is still largely unknown in the vascular physio-pathology. Taking advantage of next-generation sequencing techniques, transcriptomic changes induced by endothelial cell exposure to hypoxia were investigated. Paired-end sequencing of polyadenylated RNA derived from human umbilical vein endothelial cells (HUVECs) exposed to 1% O2 or normoxia was performed. Bioinformatics analysis identified ≈2000 differentially expressed genes, including 122 lncRNAs. Extensive validation was performed by both microarray and qPCR. Among the validated lncRNAs, H19, MIR210HG, MEG9, MALAT1 and MIR22HG were also induced in a mouse model of hindlimb ischemia. To test the functional relevance of lncRNAs in endothelial cells, knockdown of H19 expression was performed. H19 inhibition decreased HUVEC growth, inducing their accumulation in G1 phase of the cell cycle; accordingly, p21 (CDKN1A) expression was increased. Additionally, H19 knockdown also diminished HUVEC ability to form capillary like structures when plated on matrigel. In conclusion, a high-confidence signature of lncRNAs modulated by hypoxia in HUVEC was identified and a significant impact of H19 lncRNA was shown.
- Published
- 2017
13. miR-210 Enhances the Therapeutic Potential of Bone-Marrow-Derived Circulating Proangiogenic Cells in the Setting of Limb Ischemia
- Author
-
Besnier, Marie, primary, Gasparino, Stefano, additional, Vono, Rosa, additional, Sangalli, Elena, additional, Facoetti, Amanda, additional, Bollati, Valentina, additional, Cantone, Laura, additional, Zaccagnini, Germana, additional, Maimone, Biagina, additional, Fuschi, Paola, additional, Da Silva, Daniel, additional, Schiavulli, Michele, additional, Aday, Sezin, additional, Caputo, Massimo, additional, Madeddu, Paolo, additional, Emanueli, Costanza, additional, Martelli, Fabio, additional, and Spinetti, Gaia, additional
- Published
- 2018
- Full Text
- View/download PDF
14. Overexpression of miR-210 and its significance in ischemic tissue damage
- Author
-
Zaccagnini, Germana, Maimone, Biagina, Fuschi, Paola, Maselli, Davide, Spinetti, Gaia, Gaetano, Carlo, Martelli, Fabio, Zaccagnini, Germana, Maimone, Biagina, Fuschi, Paola, Maselli, Davide, Spinetti, Gaia, Gaetano, Carlo, and Martelli, Fabio
- Abstract
Hypoxia-induced miR-210 displays a pro-survival, cytoprotective and pro-angiogenic role in several in vitro systems. In vivo, we previously found that miR-210 inhibition increases ischemic damage. Here we describe the generation of a versatile transgenic mouse model allowing the evaluation of miR-210 therapeutic potential in ischemic cardiovascular diseases. We generated a Tet-On miR-210 transgenic mouse strain (TG-210) by targeted transgenesis in the ROSA26 locus. To functionally validate miR-210 transgenic mice, hindlimb ischemia was induced by femoral artery dissection. Blood perfusion was evaluated by power Doppler while tissue damage and inflammation were assessed by histological evaluation. We found that miR-210 levels were rapidly increased in TG-210 mice upon doxycycline administration. miR-210 overexpression was maintained over time and remained within physiological levels in multiple tissues. When hindlimb ischemia was induced, miR-210 overexpression protected from both muscular and vascular ischemic damage, decreased inflammatory cells density and allowed to maintain a better calf perfusion. In conclusion, we generated and functionally validated a miR-210 transgenic mouse model. Albeit validated in the context of a specific cardiovascular ischemic disease, miR-210 transgenic mice may also represent a useful model to assess the function of miR-210 in other physio-pathological conditions.
- Published
- 2017
15. Long noncoding RNA dysregulation in ischemic heart failure
- Author
-
Greco, Simona, Zaccagnini, Germana, Perfetti, Alessandra, Fuschi, Paola, Valaperta, Rea, Voellenkle, Christine, Castelvecchio, Serenella, Gaetano, Carlo, Finato, Nicoletta, Beltrami, Antonio Paolo, Menicanti, Lorenzo, Martelli, Fabio, Greco, Simona, Zaccagnini, Germana, Perfetti, Alessandra, Fuschi, Paola, Valaperta, Rea, Voellenkle, Christine, Castelvecchio, Serenella, Gaetano, Carlo, Finato, Nicoletta, Beltrami, Antonio Paolo, Menicanti, Lorenzo, and Martelli, Fabio
- Abstract
Background: Long noncoding RNAs (lncRNAs) are non-protein coding transcripts regulating a variety of physiological and pathological functions. However, their implication in heart failure is still largely unknown. The aim of this study is to identify and characterize lncRNAs deregulated in patients affected by ischemic heart failure. Methods: LncRNAs were profiled and validated in left ventricle biopsies of 18 patients affected by non end-stage dilated ischemic cardiomyopathy and 17 matched controls. Further validations were performed in left ventricle samples derived from explanted hearts of end-stage heart failure patients and in a mouse model of cardiac hypertrophy, obtained by transverse aortic constriction. Peripheral blood mononuclear cells of heart failure patients were also analyzed. LncRNA distribution in the heart was assessed by in situ hybridization. Function of the deregulated lncRNA was explored analyzing the expression of the neighbor mRNAs and by gene ontology analysis of the correlating coding transcripts. Results: Fourteen lncRNAs were significantly modulated in non end-stage heart failure patients, identifying a heart failure lncRNA signature. Nine of these lncRNAs (CDKN2B-AS1/ANRIL, EGOT, H19, HOTAIR, LOC285194/TUSC7, RMRP, RNY5, SOX2-OT and SRA1) were also confirmed in end-stage failing hearts. Intriguingly, among the conserved lncRNAs, h19, rmrp and hotair were also induced in a mouse model of heart hypertrophy. CDKN2B-AS1/ANRIL, HOTAIR and LOC285194/TUSC7 showed similar modulation in peripheral blood mononuclear cells and heart tissue, suggesting a potential role as disease biomarkers. Interestingly, RMRP displayed a ubiquitous nuclear distribution, while H19 RNA was more abundant in blood vessels and was both cytoplasmic and nuclear. Gene ontology analysis of the mRNAs displaying a significant correlation in expression with heart failure lncRNAs identified numerous pathways and functions involved in heart failure progression. Conclusions: Thes
- Published
- 2017
16. MOESM2 of Long noncoding RNA dysregulation in ischemic heart failure
- Author
-
Greco, Simona, Zaccagnini, Germana, Perfetti, Alessandra, Fuschi, Paola, Valaperta, Rea, Voellenkle, Christine, Castelvecchio, Serenella, Gaetano, Carlo, Finato, Nicoletta, Beltrami, Antonio, Menicanti, Lorenzo, and Martelli, Fabio
- Abstract
Additional file 2: Figure S1. Cardiac hypertrophy of non end-stage patients. Sections were derived from FFPE LV biopsies of controls (A) and HF patients (B). Hematoxylin and eosin staining showed a clear cardiomyocyte hypertrophy. Representative pictures are shown (HF n=16; CTR n=4; calibration bar=100 µm; magnification 20X). The bar graphs show the RT-qPCR measurement of MYH6 and NPPA hypertrophy markers, that are down- and up-regulated as expected (HF=10; CTR=5; **p≤0.01; *** p≤0.001) (C and D). Figure S2: Quality control of RNA extracted from heart biopsies of patients and controls. Total RNA was extracted from LV samples derived from non end-stage HF (n=18, panel A), end-stage HF (n=11, panel B) or controls (n=17, panel C). Integrity and amount of RNAs were measured by Bioanalyzer electrophoresis. Representative patterns and RNA Integrity Numbers (RIN) are shown. Figure S3: LncRNAs profiling in non end-stage HF patients. (A) Profiling of lncRNAs by RT-qPCR in 13 HF patients and 12 age-and sex-matched controls. (B) Validation of significantly deregulated lncRNAs in 18 HF and 17 controls. The bar graph (A) and table (B) shows the average fold change values with respect to controls (*p≤0.05, **p≤0.01; *** p≤0.001). Figure S4: Transverse aortic constriction induces cardiac hypertrophy. LV pressure overload was induced by TAC in C57BL/6J mice and cardiac hypertrophy markers were measured by RT-qPCR, 7 days after surgery. As expected atp2a2 was down- modulated and nppa, nppb and acta were increased (TAC=10; CTR=8; *p≤0.05, **p≤0.01). Figure S5: Mouse-human genomic alignment of HF lncRNAs. Gene locations from GRCh38.p5 (GCA_000001405.20) and from GRCm38.p4 (GCA_000001635.6) human and mouse genome assemblies, respectively, were used to compare the lncRNA sequence alignment in human and mouse by using Clustal Omega (http://www.ebi.ac.uk/Tools/msa/clustalo/). The percentage of identity is indicated. Figure S6: LncRNA/mRNA correlation analysis in HF. HF lncRNAs levels correlated to the levels of the mRNA expressed in the same samples. The bar graph indicates the number of transcripts significantly correlated for each lncRNA, either positively (white) or negatively (black). Figure S7: Venn’s diagram of enriched pathways in common between LV and PBMCs in HF patients GSE26887, GSE9128 and GSE1869 GEO datasets. The comparison of the 89, 99 and 53 enriched pathways of GSE26887, GSE9128 and GSE1869 datasets, respectively, identified 43 enriched pathways in common. Transcriptomic changes observed in LV and PBMCs of HF patients were determined in the following GEO datasets: for LV, GSE26887, and for PBMCs, GSE9128 and GSE1869. Common deregulated pathways were plotted as a Venn’s diagram.
- Published
- 2016
- Full Text
- View/download PDF
17. Long noncoding RNA dysregulation in ischemic heart failure
- Author
-
Greco, Simona, primary, Zaccagnini, Germana, additional, Perfetti, Alessandra, additional, Fuschi, Paola, additional, Valaperta, Rea, additional, Voellenkle, Christine, additional, Castelvecchio, Serenella, additional, Gaetano, Carlo, additional, Finato, Nicoletta, additional, Beltrami, Antonio Paolo, additional, Menicanti, Lorenzo, additional, and Martelli, Fabio, additional
- Published
- 2016
- Full Text
- View/download PDF
18. microRNAs in ischaemic cardiovascular diseases
- Author
-
Greco, Simona, primary, Zaccagnini, Germana, additional, Voellenkle, Christine, additional, and Martelli, Fabio, additional
- Published
- 2016
- Full Text
- View/download PDF
19. Magnetic resonance imaging allows the evaluation of tissue damage and regeneration in a mouse model of critical limb ischemia
- Author
-
Zaccagnini, Germana, Palmisano, Anna, Canu, Tamara, Maimone, Biagina, Lo Russo, Francesco M., Ambrogi, Federico, Gaetano, Carlo, De Cobelli, Francesco, Del Maschio, Alessandro, Esposito, Antonio, Martelli, Fabio, Zaccagnini, Germana, Palmisano, Anna, Canu, Tamara, Maimone, Biagina, Lo Russo, Francesco M., Ambrogi, Federico, Gaetano, Carlo, De Cobelli, Francesco, Del Maschio, Alessandro, Esposito, Antonio, and Martelli, Fabio
- Abstract
Magnetic resonance imaging (MRI) provides non-invasive, repetitive measures in the same individual, allowing the study of a physio-pathological event over time. In this study, we tested the performance of 7 Tesla multi-parametric MRI to monitor the dynamic changes of mouse skeletal muscle injury and regeneration upon acute ischemia induced by femoral artery dissection. T2-mapping (T2 relaxation time), diffusion-tensor imaging (Fractional Anisotropy) and perfusion by Dynamic Contrast-Enhanced MRI (K-trans) were measured and imaging results were correlated with histological morphometric analysis in both Gastrocnemius and Tibialis anterior muscles. We found that tissue damage positively correlated with T2-relaxation time, while myofiber regeneration and capillary density positively correlated with Fractional Anisotropy. Interestingly, K-trans positively correlated with capillary density. Accordingly, repeated MRI measurements between day 1 and day 28 after surgery in ischemic muscles showed that: 1) T2-relaxation time rapidly increased upon ischemia and then gradually declined, returning almost to basal level in the last phases of the regeneration process; 2) Fractional Anisotropy dropped upon ischemic damage induction and then recovered along with muscle regeneration and neoangiogenesis; 3) K-trans reached a minimum upon ischemia, then progressively recovered. Overall, Gastrocnemius and Tibialis anterior muscles displayed similar patterns of MRI parameters dynamic, with more marked responses and less variability in Tibialis anterior. We conclude that MRI provides quantitative information about both tissue damage after ischemia and the subsequent vascular and muscle regeneration, accounting for the differences between subjects and, within the same individual, between different muscles.
- Published
- 2015
20. Magnetic Resonance Imaging Allows the Evaluation of Tissue Damage and Regeneration in a Mouse Model of Critical Limb Ischemia
- Author
-
Zaccagnini, Germana, primary, Palmisano, Anna, additional, Canu, Tamara, additional, Maimone, Biagina, additional, Lo Russo, Francesco M., additional, Ambrogi, Federico, additional, Gaetano, Carlo, additional, De Cobelli, Francesco, additional, Del Maschio, Alessandro, additional, Esposito, Antonio, additional, and Martelli, Fabio, additional
- Published
- 2015
- Full Text
- View/download PDF
21. Proliferation of Multiple Cell Types in the Skeletal Muscle Tissue Elicited by Acute p21 Suppression
- Author
-
Biferi, Maria Grazia, primary, Nicoletti, Carmine, additional, Falcone, Germana, additional, Puggioni, Eleonora M R, additional, Passaro, Nunzia, additional, Mazzola, Alessia, additional, Pajalunga, Deborah, additional, Zaccagnini, Germana, additional, Rizzuto, Emanuele, additional, Auricchio, Alberto, additional, Zentilin, Lorena, additional, De Luca, Gabriele, additional, Giacca, Mauro, additional, Martelli, Fabio, additional, Musio, Antonio, additional, Musarò, Antonio, additional, and Crescenzi, Marco, additional
- Published
- 2015
- Full Text
- View/download PDF
22. GMP-based CD133+ cells isolation maintains progenitor angiogenic properties and enhances standardization in cardiovascular cell therapy
- Author
-
Gaipa, Giuseppe, primary, Tilenni, Manuela, additional, Straino, Stefania, additional, Burba, Ilaria, additional, Zaccagnini, Germana, additional, Belotti, Daniela, additional, Biagi, Ettore, additional, Valentini, Marco, additional, Perseghin, Paolo, additional, Parma, Matteo, additional, Campli, Cristiana Di, additional, Biondi, Andrea, additional, Capogrossi, Maurizio C., additional, Pompilio, Giulio, additional, and Pesce, Maurizio, additional
- Published
- 2009
- Full Text
- View/download PDF
23. p66ShcA modulates oxidative stress and survival of endothelial progenitor cells in response to high glucose
- Author
-
Di Stefano, Valeria, primary, Cencioni, Chiara, additional, Zaccagnini, Germana, additional, Magenta, Alessandra, additional, Capogrossi, Maurizio C., additional, and Martelli, Fabio, additional
- Published
- 2009
- Full Text
- View/download PDF
24. p66ShcA and Oxidative Stress Modulate Myogenic Differentiation and Skeletal Muscle Regeneration after Hind Limb Ischemia
- Author
-
Zaccagnini, Germana, primary, Martelli, Fabio, additional, Magenta, Alessandra, additional, Cencioni, Chiara, additional, Fasanaro, Pasquale, additional, Nicoletti, Carmine, additional, Biglioli, Paolo, additional, Pelicci, Pier Giuseppe, additional, and Capogrossi, Maurizio C., additional
- Published
- 2007
- Full Text
- View/download PDF
25. Telomerase Mediates Vascular Endothelial Growth Factor-dependent Responsiveness in a Rat Model of Hind Limb Ischemia
- Author
-
Zaccagnini, Germana, primary, Gaetano, Carlo, additional, Della Pietra, Linda, additional, Nanni, Simona, additional, Grasselli, Annalisa, additional, Mangoni, Antonella, additional, Benvenuto, Roberta, additional, Fabrizi, Manuela, additional, Truffa, Silvia, additional, Germani, Antonia, additional, Moretti, Fabiola, additional, Pontecorvi, Alfredo, additional, Sacchi, Ada, additional, Bacchetti, Silvia, additional, Capogrossi, Maurizio C., additional, and Farsetti, Antonella, additional
- Published
- 2005
- Full Text
- View/download PDF
26. p66 ShcA Modulates Tissue Response to Hindlimb Ischemia
- Author
-
Zaccagnini, Germana, primary, Martelli, Fabio, additional, Fasanaro, Pasquale, additional, Magenta, Alessandra, additional, Gaetano, Carlo, additional, Di Carlo, Anna, additional, Biglioli, Paolo, additional, Giorgio, Marco, additional, Martin-Padura, Ines, additional, Pelicci, Pier Giuseppe, additional, and Capogrossi, Maurizio C., additional
- Published
- 2004
- Full Text
- View/download PDF
27. Increased Production of Mouse Embryos in In Vitro Fertilization by Preincubating Sperm Cells with the Nuclease Inhibitor Aurintricarboxylic Acid1
- Author
-
Zaccagnini, Germana, primary, Maione, Barbara, additional, Lorenzini, Rodolfo, additional, and Spadafora, Corrado, additional
- Published
- 1998
- Full Text
- View/download PDF
28. GMP-based CD133+ cells isolation maintains progenitor angiogenic properties and enhances standardization in cardiovascular cell therapy.
- Author
-
Gaipa, Giuseppe, Tilenni, Manuela, Straino, Stefania, Burba, Ilaria, Zaccagnini, Germana, Belotti, Daniela, Biagi, Ettore, Valentini, Marco, Perseghin, Paolo, Parma, Matteo, Campli, Cristiana Di, Biondi, Andrea, Capogrossi, Maurizio C., Pompilio, Giulio, and Pesce, Maurizio
- Subjects
VASCULAR endothelial growth factors ,BONE marrow ,CLINICAL trials ,ISCHEMIA ,CARDIOMYOPATHIES - Abstract
The aim of the present study was to develop and validate a good manufacturing practice (GMP) compliant procedure for the preparation of bone marrow (BM) derived CD133
+ cells for cardiovascular repair. Starting from available laboratory protocols to purify CD133+ cells from human cord blood, we implemented these procedures in a GMP facility and applied quality control conditions defining purity, microbiological safety and vitality of CD133+ cells. Validation of CD133+ cells isolation and release process were performed according to a two-step experimental program comprising release quality checking (step 1) as well as ‘proofs of principle’ of their phenotypic integrity and biological function (step 2). This testing program was accomplished using in vitro culture assays and in vivo testing in an immunosuppressed mouse model of hindlimb ischemia. These criteria and procedures were successfully applied to GMP production of CD133+ cells from the BM for an ongoing clinical trial of autologous stem cells administration into patients with ischemic cardiomyopathy. Our results show that GMP implementation of currently available protocols for CD133+ cells selection is feasible and reproducible, and enables the production of cells having a full biological potential according to the most recent quality requirements by European Regulatory Agencies. [ABSTRACT FROM AUTHOR]- Published
- 2010
- Full Text
- View/download PDF
29. p66ShcA and Oxidative Stress Modulate Myogenic Differentiation and Skeletal Muscle Regeneration after Hind Limb lschemia.
- Author
-
Zaccagnini, Germana, Martelli, Fabio, Magenta, Alessandra, Cencioni, Chiara, Fasanaro, Pasquale, Nicoletti, Carmine, Biglioli, Paolo, Pelicci, Pier Giuseppe, and Capogrossi, Maurizio C.
- Subjects
- *
OXIDATIVE stress , *OXIDATION-reduction reaction , *MYOBLASTS , *CELL differentiation , *MUSCLE regeneration , *ISCHEMIA , *BIOCHEMISTRY - Abstract
Oxidative stress plays a pivotal role in ischemic injury, and p66ShcAko mice exhibit both lower oxidative stress and decreased tissue damage following hind limb ischemia. Thus, it was investigated whether tissue regeneration following acute hind limb ischemia was altered in p66ShcAko mice. Upon femoral artery dissection, muscle regeneration started earlier and was completed faster than in wild-type (WT) control. Moreover, faster regeneration was associated with decreased oxidative stress. Unlike ischemia, cardiotoxin injury induced similar skeletal muscle damage in both genotypes. However, p66ShcAko mice regenerated faster, in agreement with the regenerative advantage upon ischemia. Since no difference between p66ShcAwt and knock-out (ko) mice was found in blood perfusion recovery after ischemia, satellite cells (SCs), a resident population of myogenic progenitors, were examined. Similar SCs numbers were present in WT and ko mice. However, in vitro cultured p66ShcAko SCs displayed lower oxidative stress levels and higher proliferation rate and differentiated faster than WT, Furthermore, when exposed to sublethal H2O2 doses, p6ShcAko SCs were resistant to H2O2- induced inhibition of differentiation. Finally, myogenic conversion induced by MyoD overexpression was more efficient in p66ShcAko fibroblasts compared with WI. The present work demonstrates that oxidative stress and p66ShcA play a crucial role in the regenerative pathways activated by acute ischemia. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
30. p21Waf1/Cip1/Sdi1 mediates shear stress-dependent antiapoptotic function
- Author
-
Mattiussi, Stefania, Turrini, Paolo, Testolin, Lucia, Martelli, Fabio, Zaccagnini, Germana, Mangoni, Antonella, Barlucchi, Laura M., Antonini, Annalisa, Illi, Barbara, Cirielli, Corrado, Padron, Julio, Nicolò, Chiara, Testi, Roberto, Osculati, Francesco, Biglioli, Paolo, Capogrossi, Maurizio C., and Gaetano, Carlo
- Subjects
APOPTOSIS ,HYPOXEMIA ,ISCHEMIA ,ENDOTHELIUM - Abstract
Objective: The antiapoptotic effect of p21
Waf1/Cip1/Sdi1 (p21) was examined in human umbilical vein endothelial cells (HUVEC) exposed to laminar shear stress (SS) or to the nitric oxide donor sodium nitroprusside (SNP) and in a mouse model of hindlimb ischemia. Methods: In vitro: Cells were cultured without serum and in the presence of cobalt chloride to simulate hypoxia for 12 h (T0). Shear stress was applied to endothelial cells for additional 12 h. In vivo: Hindlimb ischemia was realized in mice by femoral artery ligation. SNP was acutely administered by subcutaneous injection or by Alzet osmotic pumps for a longer treatment. Results: At T0, HUVEC were either exposed to SS (15 dyn/cm2 /s−1 ), treated with SNP or kept in static condition (ST) for 1–12 h; after additional 12 h in ST, 30–35% of cells still alive at T0 had died. In this condition, both SS and SNP treatments markedly increased p21 levels and reduced apoptosis in HUVEC. Recombinant adenoviruses carrying p21 (AdCMV.p21) or antisense p21 (AdCMV.ASp21) cDNA revealed that AdCMV.p21-infected HUVEC were protected from death while AdCMV.ASp21 reduced SS- and SNP-dependent protection from apoptosis. In mice, apoptosis was detected in endothelial cells of ischemic hindlimbs as early as 8 h after femoral artery ligation. Treatment with SNP enhanced p21 expression and protected ischemic tissue from damage. Remarkably, direct in vivo injection of AdCMV.p21 significantly reduced the number of apoptotic nuclei in the presence of ischemia. Conclusions: The present study establishes that, under our experimental conditions, (a) p21 plays an important role in SS and nitric oxide antiapoptotic effect in vitro, and (b) p21 gene transfer prevents apoptosis in vitro and in vivo, following acute interruption of blood flow. [Copyright &y& Elsevier]- Published
- 2004
- Full Text
- View/download PDF
31. Hypoxia-Induced miR-210 Is Necessary for Vascular Regeneration upon Acute Limb Ischemia.
- Author
-
Zaccagnini, Germana, Maimone, Biagina, Fuschi, Paola, Longo, Marialucia, Da Silva, Daniel, Carrara, Matteo, Voellenkle, Christine, Perani, Laura, Esposito, Antonio, Gaetano, Carlo, and Martelli, Fabio
- Subjects
- *
VENTRICULAR remodeling , *ISCHEMIA , *PERIPHERAL vascular diseases , *MYOCARDIAL infarction , *LIFE expectancy , *TRANSGENIC mice - Abstract
Critical limb ischemia is the most serious form of peripheral artery disease, characterized by severe functional consequences, difficult clinical management and reduced life expectancy. The goal of this study was to investigate the miR-210 role in the neo-angiogenic response after acute limb ischemia. Complementary approaches were used in a mouse model of hindlimb ischemia: miR-210 loss-of-function was obtained by administration of LNA-oligonucleotides anti-miR-210; for miR-210 gain-of-function, a doxycycline-inducible miR-210 transgenic mouse was used. We tested miR-210 ability to stimulate vascular regeneration following ischemia. We found that miR-210 was necessary and sufficient to stimulate blood perfusion recovery, as well as arteriolar and capillary density increase, in the ischemic muscle. To clarify the molecular events underpinning miR-210 pro-angiogenic action, the transcriptomic changes in ischemic muscles upon miR-210 blocking were analyzed. We found that miR-210 impacted the transcriptome significantly, regulating pathways and functions linked to vascular regeneration. In agreement with a pro-angiogenic role, miR-210 also improved cardiac function and left ventricular remodeling after myocardial infarction. Moreover, miR-210 blocking decreased capillary density in a Matrigel plug assay, indicating that miR-210 is necessary for angiogenesis independently of ischemia. Collectively, these data indicate that miR-210 plays a pivotal role in promoting vascular regeneration. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
32. Proliferation of multiple cell types in the skeletal muscle tissue elicited by acute p21 suppression
- Author
-
Mauro Giacca, Alberto Auricchio, Nunzia Passaro, Maria Grazia Biferi, Gabriele De Luca, Marco Crescenzi, Germana Falcone, Eleonora M. R. Puggioni, Alessia Mazzola, Emanuele Rizzuto, Antonio Musarò, Antonio Musio, Deborah Pajalunga, Lorena Zentilin, Fabio Martelli, Germana Zaccagnini, Carmine Nicoletti, Biferi, Mg, Nicoletti, C, Falcone, G, Puggioni, Em, Passaro, N, Mazzola, A, Pajalunga, D, Zaccagnini, G, Rizzuto, E, Auricchio, Alberto, Zentilin, L, De Luca, G, Giacca, M, Martelli, F, Musio, A, Musarò, A, Crescenzi, M., Biferi, Maria Grazia, Nicoletti, Carmine, Falcone, Germana, Puggioni, Eleonora M. R., Passaro, Nunzia, Mazzola, Alessia, Pajalunga, Deborah, Zaccagnini, Germana, Rizzuto, Emanuele, Zentilin, Lorena, De Luca, Gabriele, Giacca, Mauro, Martelli, Fabio, Musio, Antonio, Musarò, Antonio, and Crescenzi, Marco
- Subjects
Cellular differentiation ,Gene Expression ,Mice ,Genes, Reporter ,Transduction, Genetic ,Drug Discovery ,Myocyte ,RNA, Small Interfering ,Gene knockdown ,p21 ,Cell Cycle ,Cell Differentiation ,Skeletal ,Hyperplasia ,Cell cycle ,Dependovirus ,Dependoviru ,Immunohistochemistry ,3. Good health ,Cell biology ,Satellite Cells ,Gene Knockdown Techniques ,Fibroblast ,DNA fragmentation ,Muscle ,Molecular Medicine ,Original Article ,RNA Interference ,Genetic Vector ,Human ,Muscle Contraction ,Cyclin-Dependent Kinase Inhibitor p21 ,Cell type ,Satellite Cells, Skeletal Muscle ,Skeletal Muscle ,muscle regeneration ,cell cycle ,Genetic Vectors ,Biology ,Small Interfering ,Serogroup ,Chromosome Aberration ,Transduction ,Genetic ,medicine ,Genetics ,Animals ,Humans ,Muscle, Skeletal ,Reporter ,Molecular Biology ,Cell Proliferation ,Chromosome Aberrations ,Pharmacology ,Animal ,Cell growth ,Drug Discovery3003 Pharmaceutical Science ,Fibroblasts ,medicine.disease ,Molecular biology ,Genes ,Gene Knockdown Technique ,Mutation ,RNA - Abstract
Although in the last decades the molecular underpinnings of the cell cycle have been unraveled, the acquired knowledge has been rarely translated into practical applications. Here, we investigate the feasibility and safety of triggering proliferation in vivo by temporary suppression of the cyclin-dependent kinase inhibitor, p21. Adeno-associated virus (AAV)-mediated, acute knockdown of p21 in intact skeletal muscles elicited proliferation of multiple, otherwise quiescent cell types, notably including satellite cells. Compared with controls, p21-suppressed muscles exhibited a striking two- to threefold expansion in cellularity and increased fiber numbers by 10 days post-transduction, with no detectable inflammation. These changes partially persisted for at least 60 days, indicating that the muscles had undergone lasting modifications. Furthermore, morphological hyperplasia was accompanied by 20% increases in maximum strength and resistance to fatigue. To assess the safety of transiently suppressing p21, cells subjected to p21 knockdown in vitro were analyzed for γ-H2AX accumulation, DNA fragmentation, cytogenetic abnormalities, ploidy, and mutations. Moreover, the differentiation competence of p21-suppressed myoblasts was investigated. These assays confirmed that transient suppression of p21 causes no genetic damage and does not impair differentiation. Our results establish the basis for further exploring the manipulation of the cell cycle as a strategy in regenerative medicine.
- Published
- 2015
33. p66ShcA modulates tissue response to hindlimb ischemia.
- Author
-
Zaccagnini G, Martelli F, Fasanaro P, Magenta A, Gaetano C, Di Carlo A, Biglioli P, Giorgio M, Martin-Padura I, Pelicci PG, and Capogrossi MC
- Subjects
- Adaptor Proteins, Signal Transducing deficiency, Adaptor Proteins, Signal Transducing genetics, Animals, Apoptosis, Capillaries pathology, Cells, Cultured drug effects, Endothelial Cells drug effects, Ischemia pathology, Male, Mice, Mice, Knockout, Muscle Cells drug effects, Muscle Fibers, Skeletal pathology, Necrosis, Oxidative Stress, Phosphorylation, Protein Processing, Post-Translational, Reactive Oxygen Species, Reperfusion Injury physiopathology, Shc Signaling Adaptor Proteins, Src Homology 2 Domain-Containing, Transforming Protein 1, Thiobarbituric Acid Reactive Substances analysis, Vascular Endothelial Growth Factor A biosynthesis, Vascular Endothelial Growth Factor A genetics, Adaptor Proteins, Signal Transducing physiology, Hindlimb blood supply, Ischemia physiopathology
- Abstract
Background: Oxidative stress plays a pivotal role in ischemia and ischemia/reperfusion injury. Because p66(ShcA)-null (p66(ShcA)-/-) mice exhibit both lower levels of intracellular reactive oxygen species and increased resistance to cell death induced by oxidative stress, we investigated whether tissue damage that follows acute ischemia or ischemia/reperfusion was altered in p66(ShcA)-/- mice., Methods and Results: Unilateral hindlimb ischemia was induced by femoral artery dissection, and ischemia/reperfusion was induced with an elastic tourniquet. Both procedures caused similar changes in blood perfusion in p66(ShcA) wild-type (p66(ShcA)wt) and p66(ShcA)-/- mice. However, significant differences in tissue damage were found: p66(ShcA)wt mice displayed marked capillary density decrease and muscle fiber necrosis. In contrast, in p66(ShcA)-/- mice, minimal capillary density decrease and myofiber death were present. When apoptosis after ischemia was assayed, significantly lower levels of apoptotic endothelial cells and myofibers were found in p66(ShcA)-/- mice. In agreement with these data, both satellite muscle cells and endothelial cells isolated from p66(ShcA)-/- mice were resistant to apoptosis induced by simulated ischemia in vitro. Lower apoptosis levels after ischemia in p66(ShcA)-/- cells correlated with decreased levels of oxidative stress both in vivo and in vitro., Conclusions: p66(ShcA) plays a crucial role in the cell death pathways activated by acute ischemia and ischemia/reperfusion, indicating p66(ShcA) as a potential therapeutic target for prevention and treatment of ischemic tissue damage.
- Published
- 2004
- Full Text
- View/download PDF
34. p21(Waf1/Cip1/Sdi1) mediates shear stress-dependent antiapoptotic function.
- Author
-
Mattiussi S, Turrini P, Testolin L, Martelli F, Zaccagnini G, Mangoni A, Barlucchi LM, Antonini A, Illi B, Cirielli C, Padron J, Nicolò C, Testi R, Osculati F, Biglioli P, Capogrossi MC, and Gaetano C
- Subjects
- Adenoviridae genetics, Animals, Apoptosis drug effects, Cells, Cultured, Cyclin-Dependent Kinase Inhibitor p21, Cyclins genetics, DNA, Antisense administration & dosage, Genetic Vectors administration & dosage, Hindlimb, Humans, Ischemia drug therapy, Ischemia metabolism, Ischemia pathology, Male, Mice, Mice, Inbred Strains, Mice, Nude, Nitric Oxide Donors pharmacology, Nitroprusside pharmacology, Stress, Mechanical, Transduction, Genetic, Cyclins pharmacology, Endothelial Cells drug effects
- Abstract
Objective: The antiapoptotic effect of p21(Waf1/Cip1/Sdi1) (p21) was examined in human umbilical vein endothelial cells (HUVEC) exposed to laminar shear stress (SS) or to the nitric oxide donor sodium nitroprusside (SNP) and in a mouse model of hindlimb ischemia., Methods: In vitro: Cells were cultured without serum and in the presence of cobalt chloride to simulate hypoxia for 12 h (T0). Shear stress was applied to endothelial cells for additional 12 h. In vivo: Hindlimb ischemia was realized in mice by femoral artery ligation. SNP was acutely administered by subcutaneous injection or by Alzet osmotic pumps for a longer treatment., Results: At T0, HUVEC were either exposed to SS (15 dyn/cm2/s(-1)), treated with SNP or kept in static condition (ST) for 1-12 h; after additional 12 h in ST, 30-35% of cells still alive at T0 had died. In this condition, both SS and SNP treatments markedly increased p21 levels and reduced apoptosis in HUVEC. Recombinant adenoviruses carrying p21 (AdCMV.p21) or antisense p21 (AdCMV.ASp21) cDNA revealed that AdCMV.p21-infected HUVEC were protected from death while AdCMV.ASp21 reduced SS- and SNP-dependent protection from apoptosis. In mice, apoptosis was detected in endothelial cells of ischemic hindlimbs as early as 8 h after femoral artery ligation. Treatment with SNP enhanced p21 expression and protected ischemic tissue from damage. Remarkably, direct in vivo injection of AdCMV.p21 significantly reduced the number of apoptotic nuclei in the presence of ischemia., Conclusions: The present study establishes that, under our experimental conditions, (a) p21 plays an important role in SS and nitric oxide antiapoptotic effect in vitro, and (b) p21 gene transfer prevents apoptosis in vitro and in vivo, following acute interruption of blood flow.
- Published
- 2004
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.