47 results on '"Latronico, Michael V. G."'
Search Results
2. Genome-wide analysis of histone marks identifying an epigenetic signature of promoters and enhancers underlying cardiac hypertrophy
- Author
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Papait, Roberto, Cattaneo, Paola, Kunderfranco, Paolo, Greco, Carolina, Carullo, Pierluigi, Guffanti, Alessandro, Viganò, Valentina, Stirparo, Giuliano Giuseppe, Latronico, Michael V. G., Hasenfuss, Gerd, Ju Chen, and Condorelli, Gianluigi
- Published
- 2013
3. Long Noncoding RNA: a New Player of Heart Failure?
- Author
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Papait, Roberto, Kunderfranco, Paolo, Stirparo, Giuliano Giuseppe, Latronico, Michael V. G., and Condorelli, Gianluigi
- Published
- 2013
- Full Text
- View/download PDF
4. Epigenetics: a new mechanism of regulation of heart failure?
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Papait, Roberto, Greco, Carolina, Kunderfranco, Paolo, Latronico, Michael V. G., and Condorelli, Gianluigi
- Published
- 2013
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5. FABP3 as Biomarker of Heart Pathology
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Catalucci, Daniele, primary, Latronico, Michael V. G., additional, and Condorelli, Gianluigi, additional
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- 2014
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6. Therapeutic Use of MicroRNAs in Myocardial Diseases
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Latronico, Michael V. G. and Condorelli, Gianlugi
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- 2011
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7. MicroRNA-133 controls cardiac hypertrophy
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Care, Alessandra, Catalucci, Daniele, Felicetti, Federica, Bonci, Desiree, Addario, Antonio, Gallo, Paolo, Bang, Marie-Louise, Segnalini, Patrizia, Gu, Yusu, Dalton, Nancy D, Elia, Leonardo, Latronico, Michael V G, Hoydal, Morten, Autore, Camillo, Russo, Matteo A, Dorn, Gerald W, II, Ellingsen, Oyvind, Ruiz-Lozano, Pilar, Peterson, Kirk L, Croce, Carlo M, Peschle, Cesare, and Condorelli, Gianluigi
- Abstract
Author(s): Alessandra Care [1, 11]; Daniele Catalucci [2, 3, 11]; Federica Felicetti [1]; Desiree Bonci [1]; Antonio Addario [1]; Paolo Gallo [3, 4]; Marie-Louise Bang [2, 3]; Patrizia Segnalini [1]; [...]
- Published
- 2007
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8. MicroRNAs and cardiac pathology
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Latronico, Michael V. G. and Condorelli, Gianluigi
- Published
- 2009
9. RNA Silencing: Small RNA-Mediated Posttranscriptional Regulation of mRNA and the Implications for Heart Electropathophysiology
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LATRONICO, MICHAEL V. G. and CONDORELLI, GIANLUIGI
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- 2009
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10. MicroRNAs Control Gene Expression: Importance for Cardiac Development and Pathophysiology
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CATALUCCI, DANIELE, LATRONICO, MICHAEL V. G., and CONDORELLI, GIANLUIGI
- Published
- 2008
11. Cardiomyocytes
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Bonci, Dèsirèe, primary, Latronico, Michael V. G., additional, and Condorelli, Gianluigi, additional
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- 2003
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12. Administration of a nitric oxide synthase inhibitor does not suppress low-dose streptozotocin-induced diabetes in mice
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Papaccio, Gianpaolo, Esposito, Vincenzo, Latronico, Michael V. G., and Pisanti, Francesco Aurelio
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- 1995
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13. Regulation of Cell Size and Contractile Function by AKT in Cardiomyocytes
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LATRONICO, MICHAEL V. G., COSTINEAN, STEFAN, LAVITRANO, MARIA LUISA, PESCHLE, CESARE, and CONDORELLI, GIANLUIGI
- Published
- 2004
14. Corrigendum: 3D hydrogel environment rejuvenates aged pericytes for skeletal muscle tissue engineering
- Author
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Fuoco, Claudia, primary, Sangalli, Elena, additional, Vono, Rosa, additional, Testa, Stefano, additional, Sacchetti, Benedetto, additional, Latronico, Michael V. G., additional, Bernardini, Sergio, additional, Madeddu, Paolo, additional, Cesareni, Gianni, additional, Seliktar, Dror, additional, Rizzi, Roberto, additional, Bearzi, Claudia, additional, Cannata, Stefano M., additional, Spinetti, Gaia, additional, and Gargioli, Cesare, additional
- Published
- 2019
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15. DNA hydroxymethylation controls cardiomyocyte gene expression in development and hypertrophy
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Greco, Carolina M., primary, Kunderfranco, Paolo, additional, Rubino, Marcello, additional, Larcher, Veronica, additional, Carullo, Pierluigi, additional, Anselmo, Achille, additional, Kurz, Kerstin, additional, Carell, Thomas, additional, Angius, Andrea, additional, Latronico, Michael V. G., additional, Papait, Roberto, additional, and Condorelli, Gianluigi, additional
- Published
- 2016
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16. 3D hydrogel environment rejuvenates aged pericytes for skeletal muscle tissue engineering
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Fuoco, Claudia, primary, Sangalli, Elena, additional, Vono, Rosa, additional, Testa, Stefano, additional, Sacchetti, Benedetto, additional, Latronico, Michael V. G., additional, Bernardini, Sergio, additional, Madeddu, Paolo, additional, Cesareni, Gianni, additional, Seliktar, Dror, additional, Rizzi, Roberto, additional, Bearzi, Claudia, additional, Cannata, Stefano M., additional, Spinetti, Gaia, additional, and Gargioli, Cesare, additional
- Published
- 2014
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17. MicroRNA-Dependent Control of the Cardiac Fibroblast Secretome
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Latronico, Michael V. G., primary and Condorelli, Gianluigi, additional
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- 2013
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18. microRNAs in hypertrophy and heart failure
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Latronico, Michael V G, primary and Condorelli, Gianluigi, additional
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- 2011
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19. MicroRNA and cardiac pathologies
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Latronico, Michael V. G., primary, Catalucci, Daniele, additional, and Condorelli, Gianluigi, additional
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- 2008
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20. Therapeutic applications of noncoding RNAs.
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Latronico, Michael V. G. and Condorelli, Gianluigi
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- 2015
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21. TNF‐α signal transduction in rat neonatal cardiac myocytes: definition of pathways generating from the TNF‐α receptor
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Condorelli, Gianluigi, primary, Morisco, Carmine, additional, Latronico, Michael V. G., additional, Claudio, Pier Paolo, additional, Dent, Paul, additional, Tsichlis, Philip, additional, Condorelli, Gerolama, additional, Frati, Giacomo, additional, Drusco, Alessandra, additional, Croce, Carlo M., additional, and Napoli, Claudio, additional
- Published
- 2002
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22. Akt induces enhanced myocardial contractility and cell size in vivo in transgenic mice
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Condorelli, Gianluigi, primary, Drusco, Alessandra, additional, Stassi, Giorgio, additional, Bellacosa, Alfonso, additional, Roncarati, Roberta, additional, Iaccarino, Guido, additional, Russo, Matteo A., additional, Gu, Yusu, additional, Dalton, Nancy, additional, Chung, Clarence, additional, Latronico, Michael V. G., additional, Napoli, Claudio, additional, Sadoshima, Junichi, additional, Croce, Carlo M., additional, and Ross, John, additional
- Published
- 2002
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23. Cardiomyocytes.
- Author
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Walker, John M., Federico, Maurizio, Bonci, Dèsirèe, Latronico, Michael V. G., and Condorelli, Gianluigi
- Abstract
Conventional ways of introducing genes into cells, such as calcium phosphate transfections and liposome or lipofectamine-mediated methods, work poorly in cardiomyocytes. They can be useful for gene reporter studies, but are of little value when a gene needs to be introduced into a large number of cardiac cells. Therefore, viral vectors are used to achieve this goal. Type 5 adenoviruses work well in cardiomyocytes, but they are hard to produce, and moreover, their immunogenicity prevents their use in long-term in vivo experiments (1). The adeno-associated virus is suitable for in vivo myocardial gene transduction because of its low or absent immunogenic potential (1), but its use for in vitro studies is limited by the low gene expression achieved (less then 10% in cardiomyocytes) (2). The classical retroviral systems are of no practical value either for studies of growth-arrested cardiomyocytes owing to the requirement of M phase for integration with host genomic DNA. Lentiviruses, however, can enter the nucleus even without mitosis (3), and recently, a new variant of third generation lentivirus ("advanced" generation) has been described (4) in which sequences of the pol gene of human immunodeficiency virus type 1 (HIV-1), central polypurine tract (cPPT) and of the posttranscriptional regulatory element of woodchuck hepatitis virus (WPRE) have been inserted. The cPPT is a cis element that has been associated with increased gene expression in growth-arrested human hematopoietic progenitor cells (4). [ABSTRACT FROM AUTHOR]
- Published
- 2003
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24. Akt Increases Sarcoplasmic Reticulum Ca2+ Cycling by Direct Phosphorylation of Phospholamban at Thr17.
- Author
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Catalucci, Daniele, Latronico, Michael V. G., Ceci, Marcello, Rusconi, Francesca, Young, Howard S., Gallo, Paolo, Santonastasi, Marco, Bellacosa, Alfonso, Brown, Joan Heller, and Condorelli, Gianluigi
- Subjects
- *
HEART cells , *CELL physiology , *PHYSIOLOGICAL adaptation , *SARCOPLASMIC reticulum , *BIOLOGICAL assay , *PHOSPHORYLATION , *HYPERTROPHY , *LABORATORY mice - Abstract
Cardiomyocytes adapt to physical stress by increasing their size while maintaining cell function. The serine/threonine kinase Akt plays a critical role in this process of adaptation. We previously reported that transgenic overexpression of an active form of Akt (Akt-E4AI)K) in mice results in increased cardiac contractility and cell size, as well as improved sarcoplasmic reticulum (SR) Ca2+ handling. Because it is not fully elucidated, we decided to study the molecular mechanism by which Akt-E40K overexpression improves SR Ca2+ handling. To this end, SR Ca2+ uptake and the phosphorylation status of phospholamban (PLN) were evaluated in heart extracts from wild-type and Akt-E40K mice and mice harboring inducible and cardiac specffic knock-out of phosphatidylinositol-dependent kinase-1, the upstream activator of Akt. Moreover, the effect of Akt was assessed in vitro by overexpressing a mutant Akt targeted preferentially to the SR, and by biochemical assays to evaluate potential interaction with PLN. We found that when activated, Akt interacts with and phosphorylates PLN at Thr17, the Ca2+-calmodulin-dependent kinase IIδ site, whereas silencing Akt signaling, through the knock-out of phosphatidylinositol-dependent kinase-1, resulted in reduced phosphorylation of PLN at Thr17. Furthermore, overexpression of SR-targeted Akt in cardiomyocytes improved Ca2+ handling without affecting cell size. Thus, we describe here a new mechanism whereby the preferential translocation of Akt to the SR is responsible for enhancement of contractility without stimulation of hypertrophy. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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25. Circulating MicroRNAs As Potential Biomarkers of Coronary Artery Disease.
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Contu, Riccardo, Latronico, Michael V. G., and Condorelli, Gianluigi
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RNA ,CORONARY disease - Abstract
The article discusses a report by Stephan Fichtlscherer and colleagues on the relationship between levels of circulating microRNAs and human coronary artery disease (CAD).
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- 2010
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26. MTORC1 regulates cardiac function and myocyte survival through 4E-BP1 inhibition in mice.
- Author
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Denghong Zhang, Contu, Riccardo, Latronico, Michael V. G., Jian Ling Zhang, Rizzi, Roberto, Catalucci, Daniele, Miyamoto, Shigeki, Huang, Katherine, Ceci, Marcello, Yusu Gu, Dalton, Nancy D., Peterson, Kirk L., Guan, Kun-Liang, Brown, Joan Heller, Ju Chen, Sonenberg, Nahum, Condorelli, Gianluigi, Zhang, Denghong, Zhang, Jianlin, and Zhang, Jian Ling
- Subjects
- *
RAPAMYCIN , *HEART failure , *APOPTOSIS , *CARRIER proteins , *HEART cells , *HEART physiology , *ANIMAL experimentation , *CELL physiology , *CELLS , *COMPARATIVE studies , *CARDIAC hypertrophy , *RESEARCH methodology , *MEDICAL cooperation , *MICE , *MYOCARDIUM , *PHOSPHOPROTEINS , *PHOSPHORYLATION , *PROTEINS , *RESEARCH , *RESEARCH funding , *TRANSCRIPTION factors , *EVALUATION research , *DILATED cardiomyopathy , *CHEMICAL inhibitors - Abstract
Mechanistic target of rapamycin (MTOR) plays a critical role in the regulation of cell growth and in the response to energy state changes. Drugs inhibiting MTOR are increasingly used in antineoplastic therapies. Myocardial MTOR activity changes during hypertrophy and heart failure (HF). However, whether MTOR exerts a positive or a negative effect on myocardial function remains to be fully elucidated. Here, we show that ablation of Mtor in the adult mouse myocardium results in a fatal, dilated cardiomyopathy that is characterized by apoptosis, autophagy, altered mitochondrial structure, and accumulation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1). 4E-BP1 is an MTOR-containing multiprotein complex-1 (MTORC1) substrate that inhibits translation initiation. When subjected to pressure overload, Mtor-ablated mice demonstrated an impaired hypertrophic response and accelerated HF progression. When the gene encoding 4E-BP1 was ablated together with Mtor, marked improvements were observed in apoptosis, heart function, and survival. Our results demonstrate a role for the MTORC1 signaling network in the myocardial response to stress. In particular, they highlight the role of 4E-BP1 in regulating cardiomyocyte viability and in HF. Because the effects of reduced MTOR activity were mediated through increased 4E-BP1 inhibitory activity, blunting this mechanism may represent a novel therapeutic strategy for improving cardiac function in clinical HF. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
27. Circulating miR-29a, among other up-regulated microRNAs, is the only biomarker for both hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy.
- Author
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Roncarati, Roberta, Viviani Anselmi, Chiara, Losi, Maria Angela, Papa, Laura, Cavarretta, Elena, Da Costa Martins, Paula, Contaldi, Carla, Saccani Jotti, Gloria, Franzone, Anna, Galastri, Laura, Latronico, Michael V G, Imbriaco, Massimo, Esposito, Giovanni, De Windt, Leon, Betocchi, Sandro, and Condorelli, Gianluigi
- Abstract
Objectives: The purpose of this paper was to determine whether microRNAs (miRNAs) involved in myocardial remodeling were differentially expressed in the blood of hypertrophic cardiomyopathy (HCM) patients, and whether circulating miRNAs correlated with the degree of left ventricular hypertrophy and fibrosis.Background: miRNAs-small, noncoding ribonucleic acids (RNAs) that regulate gene expression by inhibiting RNA translation-modulate cellular function. Myocardial miRNAs modulate processes such as cardiomyocyte (CM) hypertrophy, excitation-contraction coupling, and apoptosis; non-CM-specific miRNAs regulate myocardial vascularization and fibrosis. Recently, the possibility that circulating miRNAs may be biomarkers of cardiovascular disease has been raised.Methods: Forty-one HCM patients were characterized with conventional transthoracic echocardiography and cardiac magnetic resonance. Peripheral plasma levels of 21 miRNAs were assessed by quantitative real-time polymerase chain reaction and were compared with levels in a control group of 41 age- and sex-matched blood donors.Results: Twelve miRNAs (miR-27a, -199a-5p, -26a, -145, -133a, -143, -199a-3p, -126-3p, -29a, -155, -30a, and -21) were significantly increased in HCM plasma. However, only 3 miRNAs (miR-199a-5p, -27a, and -29a) correlated with hypertrophy; more importantly, only miR-29a correlated also with fibrosis.Conclusions: Our data suggest that cardiac remodeling associated with HCM determines a significant release of miRNAs into the bloodstream: the circulating levels of both cardiac- and non-cardiac-specific miRNAs are significantly increased in the plasma of HCM patients. However, correlation with left ventricular hypertrophy parameters holds true for only a few miRNAs (i.e., miR-199a-5p, -27a, and -29a), whereas only miR-29a is significantly associated with both hypertrophy and fibrosis, identifying it as a potential biomarker for myocardial remodeling assessment in HCM. [ABSTRACT FROM AUTHOR]- Published
- 2014
- Full Text
- View/download PDF
28. A collagen membrane-based engineered heart tissue improves cardiac function in ischemic rat hearts
- Author
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Gabriele G. Schiattarella, Anna Tampieri, Monica Sandri, Gianluigi Condorelli, Giovanni Esposito, Roberto Rizzi, Giovanni Alfonso Chiariello, Jung Hee Levialdi Ghiron, Gianluigi Pironti, Michael V.G. Latronico, Sandri, Monica, Rizzi, Roberto, Schiattarella, GABRIELE GIACOMO, Levialdi Ghiron, Jung Hee, Latronico, Michael V. G., Pironti, Gianluigi, Chiariello, Giovanni A., Esposito, Giovanni, Tampieri, Anna, and Condorelli, Gianluigi
- Subjects
Cardiac function curve ,collagen ,Materials science ,cardiovascular ,General Engineering ,Collagen membrane ,cell adhesion ,biomaterials ,membrane ,tissue engineering ,Membrane ,Tissue engineering ,Cardiac repair ,cardiovascular system ,Cell adhesion ,Biomedical engineering - Abstract
In the relatively new field of cardiac tissue engineering, different biomaterials, methods and techniques have been tested for cardiac repair, but we are still far from the achievement of a valid model that can be tested for therapeutic goals. In this study, the authors examined the efficacy of newly preformed membranes based on collagen type I for the transplantation of cardiac cells. The membrane prototype, cross-linked with 1,4-butanediol diglycidyl ether (BDDGE) and fibronectin-enriched, gave rise to spontaneously beating heart cell constructs, 5–9 days after seeding with neonatal rat cardiac cells. This membrane was grafted, with and without beating cardiac cells, onto the infarcted area of rat models of heart failure. Seriate echocardiography, performed on rats before transplantation and at 4 and 8 weeks after transplantation, demonstrated that rats treated with collagen membranes previously seeded with beating cells showed an improvement in cardiac function after 8 weeks. These results suggest that this new type of collagen membrane can be used as vector for the transplantation of beating heart cells for the regeneration of the injured myocardium and hence represents an important potential tool for cardiac tissue repair technologies.
- Published
- 2013
29. Chemerin processing in the myocardium: A mechanism in search of a function.
- Author
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Latronico MV and Condorelli G
- Subjects
- Inflammation, Myocardium, Chemokines, Intercellular Signaling Peptides and Proteins
- Published
- 2016
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- View/download PDF
30. microRNAs in cardiovascular diseases: current knowledge and the road ahead.
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Condorelli G, Latronico MV, and Cavarretta E
- Subjects
- Animals, Genetic Therapy methods, Humans, Cardiovascular Diseases genetics, Cardiovascular Diseases therapy, Genetic Therapy trends, MicroRNAs genetics, MicroRNAs therapeutic use
- Abstract
Over the last few years, the field of microribonucleic acid (miRNA) in cardiovascular biology and disease has expanded at an incredible pace. miRNAs are themselves part of a larger family, that of non-coding RNAs, the importance of which for biological processes is starting to emerge. miRNAs are ~22-nucleotide-long RNA sequences that can legate messenger (m)RNAs at partially complementary binding sites, and hence regulate the rate of protein synthesis by altering the stability of the targeted mRNAs. In the cardiovascular system, miRNAs have been shown to be critical regulators of development and physiology. They control basic functions in virtually all cell types relevant to the cardiovascular system (such as endothelial cells, cardiac muscle, smooth muscle, inflammatory cells, and fibroblasts) and, thus, are directly involved in the pathophysiology of many cardiovascular diseases. As a result of their role in disease, they are being studied for exploitation in diagnostics, prognostics, and therapeutics. However, there are still significant obstacles that need to be overcome before they enter the clinical arena. We present here a review of the literature and outline the directions toward their use in the clinic., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
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31. Reply: Platelet reactivity is preferred over genotyping in monitoring efficacy of antiplatelet therapy.
- Author
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Anselmi CV, Briguori C, Roncarati R, Papa L, Visconti G, Focaccio A, De Micco F, Latronico MV, Pagnotta P, and Condorelli G
- Subjects
- Female, Humans, Male, Aryl Hydrocarbon Hydroxylases genetics, Coronary Artery Disease therapy, Drug-Eluting Stents, Percutaneous Coronary Intervention instrumentation, Platelet Aggregation drug effects, Platelet Aggregation Inhibitors therapeutic use, Polymorphism, Genetic, Ticlopidine analogs & derivatives
- Published
- 2014
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- View/download PDF
32. Routine assessment of on-clopidogrel platelet reactivity and gene polymorphisms in predicting clinical outcome following drug-eluting stent implantation in patients with stable coronary artery disease.
- Author
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Viviani Anselmi C, Briguori C, Roncarati R, Papa L, Visconti G, Focaccio A, De Micco F, Latronico MV, Pagnotta P, and Condorelli G
- Subjects
- Aged, Aryl Hydrocarbon Hydroxylases metabolism, Aspirin therapeutic use, Biotransformation genetics, Clopidogrel, Coronary Artery Disease diagnosis, Coronary Artery Disease mortality, Coronary Thrombosis etiology, Cytochrome P-450 CYP2C19, Decision Support Techniques, Drug Therapy, Combination, Female, Genotype, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Myocardial Infarction etiology, Patient Selection, Percutaneous Coronary Intervention adverse effects, Percutaneous Coronary Intervention mortality, Pharmacogenetics, Phenotype, Platelet Aggregation Inhibitors adverse effects, Platelet Aggregation Inhibitors pharmacokinetics, Platelet Function Tests, Predictive Value of Tests, Proportional Hazards Models, Risk Assessment, Risk Factors, Ticlopidine adverse effects, Ticlopidine pharmacokinetics, Ticlopidine therapeutic use, Time Factors, Treatment Outcome, Aryl Hydrocarbon Hydroxylases genetics, Coronary Artery Disease therapy, Drug-Eluting Stents, Percutaneous Coronary Intervention instrumentation, Platelet Aggregation drug effects, Platelet Aggregation Inhibitors therapeutic use, Polymorphism, Genetic, Ticlopidine analogs & derivatives
- Abstract
Objectives: This study sought to assess the usefulness of clopidogrel-pathway genotyping and on-treatment platelet reactivity (OTR) testing in predicting major adverse cardiac events (MACE) in stable coronary artery disease (CAD) patients receiving drug-eluting stents (DES) under dual antiplatelet (clopidogrel plus aspirin) therapy., Background: The role of pharmacogenetics and OTR in predicting MACE-death, myocardial infarction, or stent thrombosis-in stable CAD patients scheduled for DES implantation is still debated., Methods: Patients with stable CAD treated by DES implantation (n = 1,432) were genotyped with a TaqMan OpenArray (Applied Biosystems, Carlsbad, California) and assessed for OTR with the VerifyNow P2Y12 test (Accumetrics Inc., San Diego, California). Genes tested were ABCB1, CYP1A2, CYP2B6*9, CYP2C8*3, CYP2C9*2, CYP2C19, CYP3A4, CYP3A5*3, P2RY12, and PON1CYP2C19. High OTR was defined as P2Y12 reaction units ≥230. The endpoint at 12-month follow-up was MACE occurring during antiplatelet therapy., Results: All groups that were stratified for loss-of-function variants of the cytochrome P450 gene CYP2C19 had significant hazard ratios (HR) for MACE (genotypic HR: 1.41, 95% confidence interval [CI]: 1.06 to 1.89, p = 0.01; allelic HR: 1.56, 95% CI: 2.26 to 1.2, p = 0.01). Variants of other clopidogrel-pathway genes were not significantly associated with MACE. When OTR was assessed, clinical significance was found only in high-risk diabetic (HR: 2.11, 95% CI: 1.29 to 3.45, p < 0.001) and chronic kidney disease (HR: 2.03, 95% CI: 1.03 to 4.02, p = 0.04) patients., Conclusions: CYP2C19 metabolizer status is an independent predictor of MACE after DES implantation and can be used for prognostication in all stable CAD patients. High OTR, as assessed by the VerifyNow P2Y12 test, is an independent predictor of MACE only for high-risk subsets, that is, patients with diabetes or chronic kidney disease., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
33. The might of microRNA in mitochondria.
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Latronico MV and Condorelli G
- Subjects
- Animals, Male, Cell Nucleus genetics, Cell Nucleus metabolism, Genome, Mitochondrial genetics, MicroRNAs physiology, Mitochondria, Heart genetics, Mitochondria, Heart metabolism, Myocytes, Cardiac physiology
- Published
- 2012
- Full Text
- View/download PDF
34. Endothelial-to-mesenchymal transition and microRNA-21: the game is on again.
- Author
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Cavarretta E, Latronico MV, and Condorelli G
- Subjects
- Humans, Cell Transdifferentiation drug effects, Endothelium, Vascular cytology, Mesoderm cytology, MicroRNAs physiology, Transforming Growth Factor beta pharmacology
- Published
- 2012
- Full Text
- View/download PDF
35. Unexpectedly low mutation rates in beta-myosin heavy chain and cardiac myosin binding protein genes in Italian patients with hypertrophic cardiomyopathy.
- Author
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Roncarati R, Latronico MV, Musumeci B, Aurino S, Torella A, Bang ML, Jotti GS, Puca AA, Volpe M, Nigro V, Autore C, and Condorelli G
- Subjects
- Adult, Aged, Base Sequence, Cardiomyopathy, Hypertrophic epidemiology, Chest Pain epidemiology, Chest Pain genetics, Cohort Studies, DNA Mutational Analysis, Electrocardiography, Female, Humans, Italy epidemiology, Male, Middle Aged, Molecular Sequence Data, Polymorphism, Single Nucleotide, Sarcomeres genetics, Cardiac Myosins genetics, Cardiomyopathy, Hypertrophic genetics, Carrier Proteins genetics, Mutation, Myosin Heavy Chains genetics
- Abstract
Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiac disease. Fourteen sarcomeric and sarcomere-related genes have been implicated in HCM etiology, those encoding β-myosin heavy chain (MYH7) and cardiac myosin binding protein C (MYBPC3) reported as the most frequently mutated: in fact, these account for around 50% of all cases related to sarcomeric gene mutations, which are collectively responsible for approximately 70% of all HCM cases. Here, we used denaturing high-performance liquid chromatography followed by bidirectional sequencing to screen the coding regions of MYH7 and MYBPC3 in a cohort (n = 125) of Italian patients presenting with HCM. We found 6 MHY7 mutations in 9/125 patients and 18 MYBPC3 mutations in 19/125 patients. Of the three novel MYH7 mutations found, two were missense, and one was a silent mutation; of the eight novel MYBPC3 mutations, one was a substitution, three were stop codons, and four were missense mutations. Thus, our cohort of Italian HCM patients did not harbor the high frequency of mutations usually found in MYH7 and MYBPC3. This finding, coupled to the clinical diversity of our cohort, emphasizes the complexity of HCM and the need for more inclusive investigative approaches in order to fully understand the pathogenesis of this disease., (Copyright © 2011 Wiley-Liss, Inc.)
- Published
- 2011
- Full Text
- View/download PDF
36. MTORC1 regulates cardiac function and myocyte survival through 4E-BP1 inhibition in mice.
- Author
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Zhang D, Contu R, Latronico MV, Zhang J, Rizzi R, Catalucci D, Miyamoto S, Huang K, Ceci M, Gu Y, Dalton ND, Peterson KL, Guan KL, Brown JH, Chen J, Sonenberg N, and Condorelli G
- Subjects
- Adaptor Proteins, Signal Transducing, Animals, Apoptosis, Cardiomegaly etiology, Cardiomyopathy, Dilated etiology, Carrier Proteins genetics, Carrier Proteins physiology, Cell Cycle Proteins, Cell Survival, Eukaryotic Initiation Factors, Female, Male, Mechanistic Target of Rapamycin Complex 1, Mice, Mice, Inbred C57BL, Mice, Knockout, Multiprotein Complexes, Myocardium pathology, Phosphoproteins genetics, Phosphoproteins physiology, Phosphorylation, Proteins, TOR Serine-Threonine Kinases, Carrier Proteins antagonists & inhibitors, Heart physiology, Myocytes, Cardiac physiology, Phosphoproteins antagonists & inhibitors, Transcription Factors physiology
- Abstract
Mechanistic target of rapamycin (MTOR) plays a critical role in the regulation of cell growth and in the response to energy state changes. Drugs inhibiting MTOR are increasingly used in antineoplastic therapies. Myocardial MTOR activity changes during hypertrophy and heart failure (HF). However, whether MTOR exerts a positive or a negative effect on myocardial function remains to be fully elucidated. Here, we show that ablation of Mtor in the adult mouse myocardium results in a fatal, dilated cardiomyopathy that is characterized by apoptosis, autophagy, altered mitochondrial structure, and accumulation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1). 4E-BP1 is an MTOR-containing multiprotein complex-1 (MTORC1) substrate that inhibits translation initiation. When subjected to pressure overload, Mtor-ablated mice demonstrated an impaired hypertrophic response and accelerated HF progression. When the gene encoding 4E-BP1 was ablated together with Mtor, marked improvements were observed in apoptosis, heart function, and survival. Our results demonstrate a role for the MTORC1 signaling network in the myocardial response to stress. In particular, they highlight the role of 4E-BP1 in regulating cardiomyocyte viability and in HF. Because the effects of reduced MTOR activity were mediated through increased 4E-BP1 inhibitory activity, blunting this mechanism may represent a novel therapeutic strategy for improving cardiac function in clinical HF.
- Published
- 2010
- Full Text
- View/download PDF
37. microRNAs in heart disease: putative novel therapeutic targets?
- Author
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Condorelli G, Latronico MV, and Dorn GW 2nd
- Subjects
- Adult, Animals, Heart growth & development, Heart Diseases metabolism, Humans, Mice, Myocardium metabolism, RNA, Messenger metabolism, RNA-Induced Silencing Complex, Heart Diseases genetics, MicroRNAs physiology
- Abstract
microRNAs (miRs) are short, approximately 22-nucleotide-long non-coding RNAs involved in the control of gene expression. They guide ribonucleoprotein complexes that effect translational repression or messenger RNA degradation to targeted messenger RNAs. miRs were initially thought to be peculiar to the developmental regulation of the nematode worm, in which they were first described in 1993. Since then, hundreds of different miRs have been reported in diverse organisms, and many have been implicated in the regulation of physiological processes of adult animals. Of importance, misexpression of miRs has been uncovered as a pathogenic mechanism in several diseases. Here, we first outline the biogenesis and mechanism of action of miRs, and then discuss their relevance to heart biology, pathology, and medicine.
- Published
- 2010
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38. Akt increases sarcoplasmic reticulum Ca2+ cycling by direct phosphorylation of phospholamban at Thr17.
- Author
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Catalucci D, Latronico MVG, Ceci M, Rusconi F, Young HS, Gallo P, Santonastasi M, Bellacosa A, Brown JH, and Condorelli G
- Subjects
- 3-Phosphoinositide-Dependent Protein Kinases, Animals, Calcium-Binding Proteins genetics, Calcium-Calmodulin-Dependent Protein Kinase Type 2 genetics, Calcium-Calmodulin-Dependent Protein Kinase Type 2 metabolism, Cells, Cultured, Mice, Mice, Transgenic, Myocytes, Cardiac cytology, Myocytes, Cardiac metabolism, Phosphorylation, Protein Serine-Threonine Kinases metabolism, Proto-Oncogene Proteins c-akt genetics, Calcium metabolism, Calcium-Binding Proteins metabolism, Proto-Oncogene Proteins c-akt metabolism, Sarcoplasmic Reticulum metabolism, Threonine metabolism
- Abstract
Cardiomyocytes adapt to physical stress by increasing their size while maintaining cell function. The serine/threonine kinase Akt plays a critical role in this process of adaptation. We previously reported that transgenic overexpression of an active form of Akt (Akt-E40K) in mice results in increased cardiac contractility and cell size, as well as improved sarcoplasmic reticulum (SR) Ca(2+) handling. Because it is not fully elucidated, we decided to study the molecular mechanism by which Akt-E40K overexpression improves SR Ca(2+) handling. To this end, SR Ca(2+) uptake and the phosphorylation status of phospholamban (PLN) were evaluated in heart extracts from wild-type and Akt-E40K mice and mice harboring inducible and cardiac specific knock-out of phosphatidylinositol-dependent kinase-1, the upstream activator of Akt. Moreover, the effect of Akt was assessed in vitro by overexpressing a mutant Akt targeted preferentially to the SR, and by biochemical assays to evaluate potential interaction with PLN. We found that when activated, Akt interacts with and phosphorylates PLN at Thr(17), the Ca(2+)-calmodulin-dependent kinase IIdelta site, whereas silencing Akt signaling, through the knock-out of phosphatidylinositol-dependent kinase-1, resulted in reduced phosphorylation of PLN at Thr(17). Furthermore, overexpression of SR-targeted Akt in cardiomyocytes improved Ca(2+) handling without affecting cell size. Thus, we describe here a new mechanism whereby the preferential translocation of Akt to the SR is responsible for enhancement of contractility without stimulation of hypertrophy.
- Published
- 2009
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39. Inhibition of class I histone deacetylase with an apicidin derivative prevents cardiac hypertrophy and failure.
- Author
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Gallo P, Latronico MV, Gallo P, Grimaldi S, Borgia F, Todaro M, Jones P, Gallinari P, De Francesco R, Ciliberto G, Steinkühler C, Esposito G, and Condorelli G
- Subjects
- Animals, Cell Line, Cells, Cultured, Disease Models, Animal, Echocardiography, Heart Failure metabolism, Heart Failure pathology, Histone Deacetylases metabolism, Humans, Hypertrophy pathology, Hypertrophy prevention & control, Hypertrophy, Left Ventricular metabolism, Hypertrophy, Left Ventricular pathology, Myocytes, Cardiac drug effects, Myocytes, Cardiac pathology, Rats, Rats, Wistar, Enzyme Inhibitors pharmacology, Heart Failure prevention & control, Histone Deacetylase Inhibitors, Hypertrophy, Left Ventricular prevention & control, Peptides, Cyclic pharmacology
- Abstract
Aims: Recent studies have demonstrated the importance of chromatin remodelling via histone acetylation/deacetylation for the control of cardiac gene expression. Specific histone deacetylases (HDACs) can, in fact, play a positive or negative role in determining cardiac myocyte (CM) size. Here, we report on the effect on hypertrophy development of three inhibitors (HDACi) of class I HDACs., Methods and Results: The compounds were first analysed in vitro by scoring hypertrophy, expression of foetal genes, and apoptosis of neonatal rat CMs stimulated with phenylephrine, an alpha1-adrenergic agonist. This initial screening indicated that a truncated derivative of apicidin with class I HDAC specificity, denoted API-D, had the highest efficacy to toxicity ratio, and was thus selected for further analysis in vivo. Administration of this drug significantly decreased myocardial hypertrophy and foetal gene expression after 1 week of pressure overload induced by thoracic aortic constriction (TAC) in mice. After 9 weeks of TAC, when manifest heart failure is encountered, mice treated with API-D presented with significantly improved echocardiographic and haemodynamic parameters of cardiac function when compared with untreated TAC-operated mice., Conclusion: The apicidin derivative, API-D, is capable of reducing hypertrophy and, consequently, the transition to heart failure in mice subjected to TAC. Treatment with this substance, therefore, holds promise as an important therapeutic option for heart failure.
- Published
- 2008
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40. On the road to the definition of the cardiac miRNome in human disease states.
- Author
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Latronico MV and Condorelli G
- Subjects
- Animals, Cells, Cultured, Disease Progression, Heart Diseases pathology, Humans, Mice, Myocardium pathology, Cardiology trends, Heart Diseases genetics, Heart Diseases metabolism, MicroRNAs metabolism, Myocardium metabolism
- Published
- 2008
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41. Heart failure: targeting transcriptional and post-transcriptional control mechanisms of hypertrophy for treatment.
- Author
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Latronico MV, Elia L, Condorelli G, and Catalucci D
- Subjects
- Animals, Cardiomegaly metabolism, Heart Failure etiology, Heart Failure pathology, Histone Deacetylases metabolism, Humans, MicroRNAs metabolism, Cardiomegaly genetics, Heart Failure drug therapy, Heart Failure genetics, RNA Processing, Post-Transcriptional, Transcription, Genetic
- Abstract
Heart failure (HF) is a syndrome caused by diminished heart function that arises from pathologies like hypertension, infarction, and diabetes. Neurohormonal, cardiorenal and cardiocirculatory models have been developed to explain HF but they have not provided sufficient understanding for the elaboration of therapies to conquer the syndrome. In fact, even though progress has been made in improving survival, HF remains a frequent cause of hospitalization and death. Since in most forms of HF, development of the disorder is associated with an alteration of cardiomyocyte structure, perceived as an increase in heart mass due to cell hypertrophy, effort is being directed to address hypertrophy as a therapeutic target. Here, we outline recent understanding of two gene-silencing regulatory mechanisms underlying cardiomyocyte hypertrophy, i.e., transcriptional control by HDACs, and post-transcriptional control by microRNAs.
- Published
- 2008
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42. Physiological myocardial hypertrophy: how and why?
- Author
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Catalucci D, Latronico MV, Ellingsen O, and Condorelli G
- Subjects
- Animals, Cell Proliferation, Female, Humans, Hypertrophy, Insulin-Like Growth Factor I metabolism, Male, Models, Biological, Neovascularization, Pathologic, Phosphatidylinositol 3-Kinases metabolism, Pregnancy, Proto-Oncogene Proteins c-akt metabolism, Receptors, Adrenergic metabolism, Signal Transduction, Myocardium pathology
- Abstract
Cardiac hypertrophy is defined by augmentation of ventricular mass as a result of increased cardiomyocyte size, and is the adaptive response of the heart to enhanced hemodynamic loads due to either physiological stimuli (post-natal developmental growth, training, and pregnancy) or pathological states (such as hypertension, valvular insufficiency, etc). The mechanisms leading to hypertrophy during pathological and physiological states are distinct but, in general, evidence indicates that hypertrophy results from the interaction of mechanical forces and neurohormonal factors. Hemodynamic overload creates a mechanical burden on the heart and results in stretch of the myocyte and induction of gene expression of cardiac growth factors. Insulin-like growth factor 1 (IGF1) has recently been shown to be the most important cardiac growth factor involved in physiological hypertrophy. In this review, IGF1 and the pathways it triggers will be discussed.
- Published
- 2008
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43. Emerging role of microRNAs in cardiovascular biology.
- Author
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Latronico MV, Catalucci D, and Condorelli G
- Subjects
- Animals, Endothelium, Vascular growth & development, Gene Expression Regulation, Developmental physiology, Humans, Cardiovascular System growth & development, MicroRNAs physiology
- Abstract
The heart is among the most conserved organs of the body and is susceptible to defects more than any other organ. Heart malformations, in fact, occur in roughly 1% of newborns. Moreover, cardiovascular disease arising during adult life is among the main causes of morbidity and mortality in developed countries. It is not surprising, therefore, that much effort is being channeled into understanding the development, physiology, and pathology of the cardiovascular system. MicroRNAs, a newly discovered class of small ribonucleotide-based regulators of gene expression, are being implicated in an increasing number of biological processes, and the study of their role in cardiovascular biology is just beginning. Here, we briefly overview microRNAs in general and report on the recent findings regarding their importance for the heart and vasculature, in particular. The new insights that are being gained will permit not only a greater understanding of cardiovascular pathologies but also, hopefully, the development of novel therapeutic strategies.
- Published
- 2007
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44. Isolation and expansion of adult cardiac stem cells from human and murine heart.
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Messina E, De Angelis L, Frati G, Morrone S, Chimenti S, Fiordaliso F, Salio M, Battaglia M, Latronico MV, Coletta M, Vivarelli E, Frati L, Cossu G, and Giacomello A
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Animals, Cell Aggregation, Cell Differentiation, Cell Division, Cells, Cultured cytology, Child, Child, Preschool, Clone Cells cytology, Coculture Techniques, Flow Cytometry, Genes, Reporter, Humans, Immunophenotyping, Infant, Infant, Newborn, Mice, Mice, Mutant Strains, Mice, SCID, Mice, Transgenic, Middle Aged, Myocardial Contraction, Myocardial Infarction therapy, Organoids cytology, Rats, Stem Cell Transplantation, Cell Separation methods, Myocardium cytology, Myocytes, Cardiac cytology, Stem Cells cytology
- Abstract
Cardiac myocytes have been traditionally regarded as terminally differentiated cells that adapt to increased work and compensate for disease exclusively through hypertrophy. However, in the past few years, compelling evidence has accumulated suggesting that the heart has regenerative potential. Recent studies have even surmised the existence of resident cardiac stem cells, endothelial cells generating cardiomyocytes by cell contact or extracardiac progenitors for cardiomyocytes, but these findings are still controversial. We describe the isolation of undifferentiated cells that grow as self-adherent clusters (that we have termed "cardiospheres") from subcultures of postnatal atrial or ventricular human biopsy specimens and from murine hearts. These cells are clonogenic, express stem and endothelial progenitor cell antigens/markers, and appear to have the properties of adult cardiac stem cells. They are capable of long-term self-renewal and can differentiate in vitro and after ectopic (dorsal subcutaneous connective tissue) or orthotopic (myocardial infarction) transplantation in SCID beige mouse to yield the major specialized cell types of the heart: myocytes (ie, cells demonstrating contractile activity and/or showing cardiomyocyte markers) and vascular cells (ie, cells with endothelial or smooth muscle markers).
- Published
- 2004
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45. Cardiomyocytes.
- Author
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Bonci D, Latronico MV, and Condorelli G
- Subjects
- Animals, Flow Cytometry methods, Genetic Vectors, Humans, Lentivirus, Rats, Myocytes, Cardiac physiology, Transduction, Genetic methods
- Published
- 2003
- Full Text
- View/download PDF
46. TNF-alpha signal transduction in rat neonatal cardiac myocytes: definition of pathways generating from the TNF-alpha receptor.
- Author
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Condorelli G, Morisco C, Latronico MV, Claudio PP, Dent P, Tsichlis P, Condorelli G, Frati G, Drusco A, Croce CM, and Napoli C
- Subjects
- Animals, Animals, Newborn, Chromones pharmacology, Enzyme Activation drug effects, Enzyme Inhibitors pharmacology, I-kappa B Proteins genetics, I-kappa B Proteins physiology, JNK Mitogen-Activated Protein Kinases, Luciferases genetics, Luciferases metabolism, Mitogen-Activated Protein Kinases metabolism, Morpholines pharmacology, Myocardium cytology, NF-kappa B genetics, NF-kappa B metabolism, Phosphoinositide-3 Kinase Inhibitors, Phosphorylation drug effects, Proto-Oncogene Proteins metabolism, Proto-Oncogene Proteins c-akt, Rats, Rats, Wistar, Receptors, Tumor Necrosis Factor physiology, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins metabolism, Signal Transduction drug effects, Myocardium metabolism, Protein Serine-Threonine Kinases, Tumor Necrosis Factor-alpha pharmacology
- Abstract
Cardiomyocyte hypertrophy and apoptosis have been implicated in the loss of contractile function during heart failure (HF). Moreover, patients with HF have been shown to exhibit increased levels of tumor necrosis factor alpha (TNF-alpha) in the myocardium. However, the multiple signal transduction pathways generating from the TNF-alpha receptor in cardiomyocytes and leading preferentially to apoptosis or hypertrophy are still unknown. Here we demonstrate in neonatal rat cardiomyocytes that 1) TNF-alpha induces phosphorylation of AKT, activation of NF-kappaB, and the phosphorylation of JUN kinase; 2) blocking AKT activity prevents NF-kappaB activation, suggesting a role for AKT in regulating NF-kappaB function; 3) AKT and JUN are both critical for the hypertrophic effects of TNF-alpha, since dominant-negative mutants of these genes are capable of inhibiting TNF-alpha-induced ANF-promoter up-regulation and increase in cardiomyocyte cell size, and 4) blocking NF-kappaB, AKT, or JUN alone or in combination does not sensitize cardiomyocytes to the proapoptotic effects of TNF-alpha, in contrast to other cell types, suggesting a cardiac-specific pathway regulating the anti-apoptotic events induced by TNF-alpha. Altogether, the data presented evidence the role of AKT and JUN in TNF-alpha-induced cardiomyocyte hypertrophy and apoptosis.
- Published
- 2002
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- View/download PDF
47. Th1 and Th2 cytokines exert regulatory effects upon islet microvascular areas in the NOD mouse.
- Author
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Papaccio G, Pisanti FA, Montefiano RD, Graziano A, and Latronico MV
- Subjects
- Animals, Blood Glucose analysis, Cell Culture Techniques, Endothelium, Vascular cytology, Endothelium, Vascular metabolism, Female, Intercellular Adhesion Molecule-1 metabolism, Interleukins pharmacology, Islets of Langerhans cytology, Islets of Langerhans metabolism, Mice, Mice, Inbred NOD, Microcirculation physiology, Microscopy methods, Nitrates analysis, Nitric Oxide metabolism, Nitrites analysis, Oxidoreductases metabolism, RNA biosynthesis, Reverse Transcriptase Polymerase Chain Reaction, Time Factors, Cytokines physiology, Islets of Langerhans blood supply, Th1 Cells metabolism, Th2 Cells metabolism
- Abstract
In this study, we show that intra- and peri-islet microvascular areas undergo different changes during the islet inflammation in the nonobese diabetes-prone female mice. Actually, although the islet vascular area (IVA) considerably decreases while the infiltration progresses, at 15 weeks of age, the peri-islet vascular bed is unexpectedly and significantly increased. On the contrary, the intra-IVA is significantly decreased, due to vessel dilation. Later, by 20-25 weeks of age, a decrease of both IVA occur, due to a significant islet beta cell loss. Moreover, a dramatic fall of natural free radical scavenger values, which, in turn, exert an influence upon vessels, is observed. These effects are completely counteracted by the administration of IL-4, a Th2 protective cytokine; IL-10, another putative Th2 cytokine, exerts direct effects upon endothelial cell (EC) function, as shown by the increase of endothelial nitric oxide synthase (eNOS) mRNA transcripts and by the release of endothelial NO which, in turn, exert vasodilatory effects; moreover, this cytokine significantly upregulates adhesion molecules on endothelia. On the other hand, IL-1beta, a Th1 proinflammatory cytokine, dramatically increases nitrite and nitrate levels, as well as inducible nitric oxide synthase (iNOS) transcripts and also upregulates islet ICAM-1 expression as well as circulating ICAM-1 levels. Taken together, our findings clearly show that cytokines and islet endothelia are directly involved in the pathophysiology of the disease. Their reciprocal influence gives new insight to understand the role of microvasculature during islet beta cell attack., (Copyright 2002 Wiley-Liss, Inc.)
- Published
- 2002
- Full Text
- View/download PDF
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