102 results on '"Loffredo, Francesco S"'
Search Results
2. The Desmoplakin Phenotype Spectrum: Is the Inflammation the "Fil Rouge" Linking Myocarditis, Arrhythmogenic Cardiomyopathy, and Uncommon Autoinflammatory Systemic Disease?
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D'Elia, Saverio, Caputo, Adriano, Natale, Francesco, Pezzullo, Enrica, Limongelli, Giuseppe, Golino, Paolo, Cimmino, Giovanni, and Loffredo, Francesco S.
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DILATED cardiomyopathy ,HEART failure ,VENTRICULAR arrhythmia ,PHYSIOLOGICAL stress ,SYMPTOMS - Abstract
Myocarditis is an inflammatory condition of cardiac tissue presenting significant variability in clinical manifestations and outcomes. Its etiology is diverse, encompassing infectious agents (primarily viruses, but also bacteria, protozoa, and helminths) and non-infectious factors (autoimmune responses, toxins, and drugs), though often the specific cause remains unidentified. Recent research has highlighted the potential role of genetic susceptibility in the development of myocarditis (and in some cases the development of inflammatory dilated cardiomyopathy, i.e., the condition in which there is chronic inflammation (>3 months) and left ventricular dysfunction\dilatation), with several studies indicating a correlation between myocarditis and genetic backgrounds. Notably, pathogenic genetic variants linked to dilated or arrhythmic cardiomyopathy are found in 8–16% of myocarditis patients. Genetic predispositions can lead to recurrent myocarditis and a higher incidence of ventricular arrhythmias and heart failure. Moreover, the presence of DSP mutations has been associated with distinct pathological patterns and clinical outcomes in arrhythmogenic cardiomyopathy (hot phases). The interplay between genetic factors and environmental triggers, such as viral infections and physical stress, is crucial in understanding the pathogenesis of myocarditis. Identifying these genetic markers can improve the diagnosis, risk stratification, and management of patients with myocarditis, potentially guiding tailored therapeutic interventions. This review aims to synthesize current knowledge on the genetic underpinnings of myocarditis, with an emphasis on desmoplakin-related arrhythmogenic cardiomyopathy, to enhance clinical understanding and inform future research directions. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Mitophagy modulation for the treatment of cardiovascular diseases.
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Forte, Maurizio, D'Ambrosio, Luca, Schiattarella, Gabriele G., Salerno, Nadia, Perrone, Marco Alfonso, Loffredo, Francesco S., Bertero, Edoardo, Pilichou, Kalliopi, Manno, Girolamo, Valenti, Valentina, Spadafora, Luigi, Bernardi, Marco, Simeone, Beatrice, Sarto, Gianmarco, Frati, Giacomo, Perrino, Cinzia, and Sciarretta, Sebastiano
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CARDIOVASCULAR diseases ,THERAPEUTICS ,CARDIOVASCULAR system ,VASCULAR diseases ,HEART failure - Abstract
Background: Defects of mitophagy, the selective form of autophagy for mitochondria, are commonly observed in several cardiovascular diseases and represent the main cause of mitochondrial dysfunction. For this reason, mitophagy has emerged as a novel and potential therapeutic target. Methods: In this review, we discuss current evidence about the biological significance of mitophagy in relevant preclinical models of cardiac and vascular diseases, such as heart failure, ischemia/reperfusion injury, metabolic cardiomyopathy and atherosclerosis. Results: Multiple studies have shown that cardiac and vascular mitophagy is an adaptive mechanism in response to stress, contributing to cardiovascular homeostasis. Mitophagy defects lead to cell death, ultimately impairing cardiac and vascular function, whereas restoration of mitophagy by specific compounds delays disease progression. Conclusions: Despite previous efforts, the molecular mechanisms underlying mitophagy activation in response to stress are not fully characterized. A comprehensive understanding of different forms of mitophagy active in the cardiovascular system is extremely important for the development of new drugs targeting this process. Human studies evaluating mitophagy abnormalities in patients at high cardiovascular risk also represent a future challenge. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Constrictive Pericarditis After a Stab Wound of the Chest
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Del Giudice, Carmen, primary, Cosimo, Renato, additional, Caracciolo D'Aquino, Marco Malvezzi, additional, Pezzullo, Enrica, additional, Bussani, Rossana, additional, Massa, Laura, additional, Pozzan, Marco, additional, Korcova, Renata, additional, Ruggiero, Danilo, additional, Mazzaro, Enzo, additional, Sinagra, Gianfranco, additional, Golino, Paolo, additional, and Loffredo, Francesco S., additional
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- 2024
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5. Wet-dry-wet drug screen leads to the synthesis of TS1, a novel compound reversing lung fibrosis through inhibition of myofibroblast differentiation
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Ring, Nadja Anneliese Ruth, Volpe, Maria Concetta, Stepišnik, Tomaž, Mamolo, Maria Grazia, Panov, Panče, Kocev, Dragi, Vodret, Simone, Fortuna, Sara, Calabretti, Antonella, Rehman, Michael, Colliva, Andrea, Marchesan, Pietro, Camparini, Luca, Marcuzzo, Thomas, Bussani, Rossana, Scarabellotto, Sara, Confalonieri, Marco, Pham, Tho X., Ligresti, Giovanni, Caporarello, Nunzia, Loffredo, Francesco S., Zampieri, Daniele, Džeroski, Sašo, and Zacchigna, Serena
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- 2022
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6. Evolving Concepts of the SCORE System: Subtracting Cholesterol from Risk Estimation: A Way for a Healthy Longevity?
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Natale, Francesco, Franzese, Rosa, Marotta, Luigi, Mollo, Noemi, Solimene, Achille, Luisi, Ettore, Gentile, Carmine, Loffredo, Francesco S., Golino, Paolo, and Cimmino, Giovanni
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CIGARETTE smoke ,LOW density lipoproteins ,ACUTE coronary syndrome ,CHOLESTEROL ,CARDIOVASCULAR diseases risk factors ,LDL cholesterol ,NICOTINE - Abstract
The role of cholesterol, mainly low-density lipoproteins (LDL-C), as a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) is now established and accepted by the international scientific community. Based on this evidence, the European and American guidelines recommend early risk stratification and "rapid" achievement of the suggested target according to the risk estimation to reduce the number of major cardiovascular events. Prolonged exposure over the years to high levels of LDL-C is one of the determining factors in the development and progression of atherosclerotic plaque, on which the action of conventional risk factors (cigarette smoking, excess weight, sedentary lifestyle, arterial hypertension, diabetes mellitus) as well as non-conventional risk factors (gut microbiota, hyperuricemia, inflammation), alone or in combination, favors the destabilization of the atherosclerotic lesion with rupture/fissuration/ulceration and consequent formation of intravascular thrombosis, which leads to the acute clinical manifestations of acute coronary syndromes. In the current clinical practice, there is a growing number of cases that, although extremely common, are emblematic of the concept of long-term exposure to the risk factor (LDL hypercholesterolemia), which, not adequately controlled and in combination with other risk factors, has favored the onset of major cardiovascular events. The triple concept of "go lower, start earlier and keep longer!" should be applied in current clinical practice at any level of prevention. In the present manuscript, we will review the current evidence and documents supporting the causal role of LDL-C in determining ASCVD and whether it is time to remove it from any score. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Arrhythmogenic Left Ventricular Cardiomyopathy: From Diagnosis to Risk Management.
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Mauriello, Alfredo, Roma, Anna Selvaggia, Ascrizzi, Antonia, Molinari, Riccardo, Loffredo, Francesco S., D'Andrea, Antonello, and Russo, Vincenzo
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ARRHYTHMOGENIC right ventricular dysplasia ,CARDIAC magnetic resonance imaging ,CARDIOMYOPATHIES ,CARDIAC arrest ,DIAGNOSIS ,GENETIC testing - Abstract
Purpose of Review: Left ventricular arrhythmogenic cardiomyopathy (ALVC) is a rare and poorly characterized cardiomyopathy that has recently been reclassified in the group of non-dilated left ventricular cardiomyopathies. This review aims to summarize the background, diagnosis, and sudden cardiac death risk in patients presenting this cardiomyopathy. Recent Findings: Although there is currently a lack of data on this condition, arrhythmogenic left ventricular dysplasia can be considered a specific disease of the left ventricle (LV). We have collected the latest evidence about the management and the risks associated with this cardiomyopathy. Summary: Left ventricular arrhythmogenic cardiomyopathy is still poorly characterized. ALVC is characterized by fibrofatty replacement in the left ventricular myocardium, with variable phenotypic expression. Diagnosis is based on a multiparametric approach, including cardiac magnetic resonance (CMR) and genetic testing, and is important for sudden cardiac death (SCD) risk stratification and management. Recent guidelines have improved the management of left ventricular arrhythmogenic cardiomyopathy. Further studies are necessary to improve knowledge of this cardiomyopathy. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Non-Conventional Risk Factors: “Fact” or “Fake” in Cardiovascular Disease Prevention?
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Cimmino, Giovanni, primary, Natale, Francesco, additional, Alfieri, Roberta, additional, Cante, Luigi, additional, Covino, Simona, additional, Franzese, Rosa, additional, Limatola, Mirella, additional, Marotta, Luigi, additional, Molinari, Riccardo, additional, Mollo, Noemi, additional, Loffredo, Francesco S, additional, and Golino, Paolo, additional
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- 2023
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9. Exogenous GDF11, but not GDF8, reduces body weight and improves glucose homeostasis in mice
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Walker, Ryan G., Barrandon, Ornella, Poggioli, Tommaso, Dagdeviren, Sezin, Carroll, Shannon H., Mills, Melanie J., Mendello, Kourtney R., Gomez, Yanet, Loffredo, Francesco S., Pancoast, James R., Macias-Trevino, Claudio, Marts, Colin, LeClair, Katherine B., Noh, Hye-Lim, Kim, Taekyoon, Banks, Alexander S., Kim, Jason K., Cohen, David E., Wagers, Amy J., Melton, Douglas A., and Lee, Richard T.
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- 2020
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10. Echocardiographic evaluation of centenarians in Trieste
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Cannatà, Antonio, Gentile, Piero, Paldino, Alessia, Nuzzi, Vincenzo, Camparini, Luca, Ciucci, Giulio, Manca, Paolo, Artico, Jessica, Dal Ferro, Matteo, Marcon, Gabriella, Tettamanti, Mauro, Merlo, Marco, Sinagra, Gianfranco, and Loffredo, Francesco S.
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- 2020
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11. Engineered heart tissue maturation inhibits cardiomyocyte proliferative response to cryoinjury.
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Ciucci, Giulio, Rahhali, Karim, Cimmino, Giovanni, Natale, Francesco, Golino, Paolo, Sinagra, Gianfranco, Collesi, Chiara, and Loffredo, Francesco S
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HEART ,CARDIAC regeneration ,DNA synthesis ,MYOCARDIAL infarction ,MYOCARDIAL injury ,TISSUES ,IMMUNE system - Abstract
The cellular and molecular mechanisms that are responsible for the poor regenerative capacity of the adult heart after myocardial infarction (MI) are still unclear and their understanding is crucial to develop novel regenerative therapies. Considering the lack of reliable in vitro tissue-like models to evaluate the molecular mechanisms of cardiac regeneration, we used cryoinjury on rat Engineered Heart Tissues (rEHTs) as a new model which recapitulates in part the in vivo response after myocardial injury of neonatal and adult heart. When we subjected to cryoinjury immature and mature rEHTs, we observed a significant increase in cardiomyocyte (CM) DNA synthesis when compared to the controls. As expected, the number of mitotic CMs significantly increases in immature rEHTs when compared to mature rEHTs, suggesting that the extent of CM maturation plays a crucial role in their proliferative response after cryoinjury. Moreover, we show that cryoinjury induces a temporary activation of fibroblast response in mature EHTs, similar to the early response after MI, that is however incomplete in immature EHTs. Our results support the hypothesis that the endogenous maturation program in cardiac myocytes plays a major role in determining the proliferative response to injury. Therefore, we propose rEHTs as a robust, novel tool to in vitro investigate critical aspects of cardiac regeneration in a tissue-like asset free from confounding factors in response to injury, such as the immune system response or circulating inflammatory cytokines. [ABSTRACT FROM AUTHOR]
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- 2023
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12. Colchicine in Athero-Thrombosis: Molecular Mechanisms and Clinical Evidence
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Cimmino, Giovanni, primary, Loffredo, Francesco S., additional, De Rosa, Gennaro, additional, and Cirillo, Plinio, additional
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- 2023
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13. Catch the Cath or Not? A Hamletic Dilemma after 10 Years
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Natale, Francesco, primary, Raucci, Giuseppe, additional, Molinari, Riccardo, additional, Alfieri, Roberta, additional, D’Arienzo, Diego, additional, Pezzullo, Enrica, additional, Loffredo, Francesco S, additional, Golino, Paolo, additional, and Cimmino, Giovanni, additional
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- 2023
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14. Restoring Systemic GDF11 Levels Reverses Age-Related Dysfunction in Mouse Skeletal Muscle
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Sinha, Manisha, Jang, Young C., Oh, Juhyun, Khong, Danika, Wu, Elizabeth Y., Manohar, Rohan, Miller, Christine, Regalado, Samuel G., Loffredo, Francesco S., Pancoast, James R., Hirshman, Michael F., Lebowitz, Jessica, Shadrach, Jennifer L., Cerletti, Massimiliano, Kim, Mi-Jeong, Serwold, Thomas, Goodyear, Laurie J., Rosner, Bernard, Lee, Richard T., and Wagers, Amy J.
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- 2014
15. Vascular and Neurogenic Rejuvenation of the Aging Mouse Brain by Young Systemic Factors
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Katsimpardi, Lida, Litterman, Nadia K., Schein, Pamela A., Miller, Christine M., Loffredo, Francesco S., Wojtkiewicz, Gregory R., Chen, John W., Lee, Richard T., Wagers, Amy J., and Rubin, Lee L.
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- 2014
16. Growth Differentiation Factor 11 Is a Circulating Factor that Reverses Age-Related Cardiac Hypertrophy
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Loffredo, Francesco S., Steinhauser, Matthew L., Jay, Steven M., Gannon, Joseph, Pancoast, James R., Yalamanchi, Pratyusha, Sinha, Manisha, Dall’Osso, Claudia, Khong, Danika, Shadrach, Jennifer L., Miller, Christine M., Singer, Britta S., Stewart, Alex, Psychogios, Nikolaos, Gerszten, Robert E., Hartigan, Adam J., Kim, Mi-Jeong, Serwold, Thomas, Wagers, Amy J., and Lee, Richard T.
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- 2013
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17. Bone Marrow-Derived Cell Therapy Stimulates Endogenous Cardiomyocyte Progenitors and Promotes Cardiac Repair
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Loffredo, Francesco S., Steinhauser, Matthew L., Gannon, Joseph, and Lee, Richard T.
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- 2011
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18. Wet-dry-wet drug screen leads to the synthesis of TS1, a novel compound reversing lung fibrosis through inhibition of myofibroblast differentiation
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Ring, Nadja Anneliese Ruth, primary, Volpe, Maria Concetta, additional, Stepišnik, Tomaž, additional, Mamolo, Maria Grazia, additional, Panov, Panče, additional, Kocev, Dragi, additional, Vodret, Simone, additional, Fortuna, Sara, additional, Calabretti, Antonella, additional, Rehman, Michael, additional, Colliva, Andrea, additional, Marchesan, Pietro, additional, Camparini, Luca, additional, Marcuzzo, Thomas, additional, Bussani, Rossana, additional, Scarabellotto, Sara, additional, Confalonieri, Marco, additional, Pham, Tho X., additional, Ligresti, Giovanni, additional, Caporarello, Nunzia, additional, Loffredo, Francesco S., additional, Zampieri, Daniele, additional, Džeroski, Sašo, additional, and Zacchigna, Serena, additional
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- 2021
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19. Targeted Delivery to Cartilage Is Critical for In Vivo Efficacy of Insulin-like Growth Factor 1 in a Rat Model of Osteoarthritis
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Loffredo, Francesco S., Pancoast, James R., Cai, Lei, Vannelli, Todd, Dong, Jesse Z., Lee, Richard T., and Patwari, Parth
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- 2014
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20. Peripheral Artery Disease and Abdominal Aortic Aneurysm: The Forgotten Diseases in COVID-19 Pandemic. Results from an Observational Study on Real-World Management
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Natale, Francesco, primary, Capasso, Raffaele, additional, Casalino, Alfonso, additional, Crescenzi, Clotilde, additional, Sangiuolo, Paolo, additional, Golino, Paolo, additional, Loffredo, Francesco S., additional, and Cimmino, Giovanni, additional
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- 2021
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21. Percutaneous Left Atrial Appendage Occlusion: An Emerging Option in Patients with Atrial Fibrillation at High Risk of Bleeding
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Cimmino, Giovanni, primary, Loffredo, Francesco S., additional, Gallinoro, Emanuele, additional, Prozzo, Dario, additional, Fabiani, Dario, additional, Cante, Luigi, additional, Salerno, Gemma, additional, Cappelli Bigazzi, Maurizio, additional, and Golino, Paolo, additional
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- 2021
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22. Targeted Approach to Distinguish and Determine Absolute Levels of GDF8 and GDF11 in Mouse Serum
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Camparini, Luca, primary, Kollipara, Laxmikanth, additional, Sinagra, Gianfranco, additional, Loffredo, Francesco S., additional, Sickmann, Albert, additional, and Shevchuk, Olga, additional
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- 2020
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23. Colchicine reduces platelet aggregation by modulating cytoskeleton rearrangement via inhibition of cofilin and LIM domain kinase 1
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Cimmino, Giovanni, primary, Tarallo, Roberta, additional, Conte, Stefano, additional, Morello, Andrea, additional, Pellegrino, Grazia, additional, Loffredo, Francesco S., additional, Calì, Gaetano, additional, De Luca, Nicola, additional, Golino, Paolo, additional, Trimarco, Bruno, additional, and Cirillo, Plinio, additional
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- 2018
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24. Immune-Inflammatory Activation in Acute Coronary Syndromes: A Look into the Heart of Unstable Coronary Plaque
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Cimmino, Giovanni, primary, Loffredo, Francesco S., additional, Morello, Alberto, additional, D'Elia, Saverio, additional, De Palma, Raffaele, additional, Cirillo, Plinio, additional, and Golino, Paolo, additional
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- 2017
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25. Role of circulating factors in cardiac aging
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Cannatà, Antonio, primary, Marcon, Gabriella, additional, Cimmino, Giovanni, additional, Camparini, Luca, additional, Ciucci, Giulio, additional, Sinagra, Gianfranco, additional, and Loffredo, Francesco S., additional
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- 2017
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26. Safety of Transesophageal Echocardiogram in Anticoagulated Patients.
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Natale, Francesco, Loffredo, Francesco S., Salerno, Gemma, Molinari, Riccardo, Pezzullo, Enrica, Golino, Paolo, and Cimmino, Giovanni
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- 2023
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27. Circulating Growth Differentiation Factor 11/8 Levels Decline With Age
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Poggioli, Tommaso, primary, Vujic, Ana, additional, Yang, Peiguo, additional, Macias-Trevino, Claudio, additional, Uygur, Aysu, additional, Loffredo, Francesco S., additional, Pancoast, James R., additional, Cho, Miook, additional, Goldstein, Jill, additional, Tandias, Rachel M., additional, Gonzalez, Emilia, additional, Walker, Ryan G., additional, Thompson, Thomas B., additional, Wagers, Amy J., additional, Fong, Yick W., additional, and Lee, Richard T., additional
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- 2016
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28. Evolving Concepts in LDL-Lowering Strategies: Are We There?
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Cimmino, Giovanni, primary, Loffredo, Francesco S, additional, Arena, Giulia, additional, and Golino, Paolo, additional
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- 2016
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29. Bone Marrow-Derived Cell Therapy Stimulates Endogenous Cardiomyocyte Progenitors and Promotes Cardiac Repair
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Loffredo, Francesco S., primary, Steinhauser, Matthew L., additional, Gannon, Joseph, additional, and Lee, Richard T., additional
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- 2015
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30. Heart Failure With Preserved Ejection Fraction
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Loffredo, Francesco S., primary, Nikolova, Andriana P., additional, Pancoast, James R., additional, and Lee, Richard T., additional
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- 2014
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31. Keep PNUTS in Your Heart
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Loffredo, Francesco S., primary, Pancoast, James R., additional, and Lee, Richard T., additional
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- 2013
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32. Pathways for salvage and protection of the heart under stress: novel routes for cardiac rejuvenation.
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Cannatà, Antonio, Camparini, Luca, Sinagra, Gianfranco, Giacca, Mauro, and Loffredo, Francesco S.
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SALVAGE therapy ,HEART ,DISEASES ,PSYCHOLOGICAL stress ,REJUVENATION ,CARDIOVASCULAR diseases risk factors ,MOLECULAR biology - Abstract
Theworld population is aging, and by 2017, there will bemore people over the age of 65 than under age 5, and by 2050, two billion of the estimated nine billion people on Earth will be older than 60. Aging itself is a major cardiovascular risk factor, affecting morbidity and mortality of the aging population. At the same time, aging increases the likelihood of the presence of other risk factors. The aged myocardium is characterized by several structural and functional progressive changes that impair its ability to respond appropriately to stressful conditions. Although some progress to understand the complex mechanisms that underlie these phenotypic changes, the molecular pathways that determine the balance between aging and rejuvenation in the aged myocardium still remain elusive. In this article, we review molecular mechanisms responsible for the phenotypic changes observed with aging in the heart, providing insight into molecular pathways and pharmacological interventions that may rejuvenate the aged myocardium. A better understanding of these pathways is essential for determining their therapeutic potential in humans, improving the possibility that the increase in life expectancy that we are observing will be accompanied by a parallel increase in healthspan. [ABSTRACT FROM AUTHOR]
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- 2016
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33. Abstract 16496: Circulating Systemic Factors from Young Mice Reverse Age-Related Cardiac Hypertrophy
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Loffredo, Francesco S, primary, Steinhauser, Matthew L, additional, Tian, Jack, additional, Gannon, Joseph, additional, Shadrach, Jennifer, additional, Miller, Christine, additional, Pizzimenti, Christie L, additional, Wagers, Amy J, additional, and Lee, Richard T, additional
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- 2011
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34. Abstract 13359: Mechanical Loading Regulates Cardiomyocytes Proliferation in Engineered Heart Tissues
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Ciucci, Giulio, Camparini, Luca, Ciacci, Lorenzo, Boer, Sara, Cimmino, Giovanni, Golino, Paolo, Sinagra, Gianfranco, and Loffredo, Francesco S
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Introduction:Mammal cardiomyocytes (CMs) lose their proliferative capacity early after birth acquiring an adult phenotype characterized by an organized sarcomeric structure, among others features. Neonatal hearts are subjected to a sudden increase in mechanical loading that may contribute to switch mammal CMs phenotype from neonatal proliferative to adult postmitotic.Hypothesis:this study will test the hypothesis that variations of mechanical loading may regulate proliferation and maturation of cardiomyocytes in an engineered heart tissue model (EHT).Methods:EHT were generated using neonatal rat heart cells and subjected to a 48h pulse of BrdU between 48 hours and 28 days post-casting, a window that corresponds to EHTs maturation. Mechanical unloading was performed by reducing the distance between the silicon posts that anchor the extremities of EHTs while the afterload was increased by changing Young?s module of posts with metal braces.Results:after an initial increase in the percentage of BrdU+CMs early after EHT casting, similarly to what is observed in mouse neonatal hearts, CMs DNA synthesis progressively decreased becoming negligible at day 28. Interestingly, the decrease of BrdU+CMs was accompanied by a progressive increase of binucleated cardiomyocytes. The increase of binucleated CMs corresponds to the beginning of a coherent and spontaneous contractile activity of EHTs that occurs around day 13, suggesting that the increasing force of contraction required may represent the trigger to switch from a pro-proliferative state to a mature phenotype. In line with our hypothesis, mechanical unloading of developed EHTs significantly increased the percentage of EdU+mononucleated CM (2,6% ? 0.94% vs. 5,2% ? 0,2%) while an increase in afterload produced a higher degree of sarcomeric organization and a reduction of proliferating CMs (1,8% ? 0,5%).Conclusions:our data indicate that EHTs may represent a valuable model to study post-natal cardiac biology and support the hypothesis that indicate mechanical loading as a master regulator of cardiomyocytes proliferation and maturation. Ongoing experiments are aimed at identifying the mechanisms that regulate this process.
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- 2019
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35. Echocardiographic evaluation of centenarians in Trieste
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Matteo Dal Ferro, Francesco S. Loffredo, Piero Gentile, Antonio Cannatà, Gianfranco Sinagra, Paolo Manca, Mauro Tettamanti, Marco Merlo, Luca Camparini, Alessia Paldino, Giulio Ciucci, Gabriella Marcon, Jessica Artico, Vincenzo Nuzzi, Cannatà, Antonio, Gentile, Piero, Paldino, Alessia, Nuzzi, Vincenzo, Camparini, Luca, Ciucci, Giulio, Manca, Paolo, Artico, Jessica, Dal Ferro, Matteo, Marcon, Gabriella, Tettamanti, Mauro, Merlo, Marco, Sinagra, Gianfranco, Loffredo, Francesco S., and Loffredo, Francesco S
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Male ,Aging ,Pediatrics ,medicine.medical_specialty ,Health Status ,Population ,Diastole ,Context (language use) ,Disease ,cardiovascular aging ,Asymptomatic ,Ventricular Function, Left ,Electrocardiography ,Predictive Value of Tests ,medicine ,Humans ,education ,special populations ,Aged, 80 and over ,education.field_of_study ,Successful aging ,business.industry ,Age Factors ,Hemodynamics ,Atrial fibrillation ,General Medicine ,medicine.disease ,Home Care Services ,Echocardiography, Doppler ,Italy ,cardiovascular aging, centenarians, diastolic dysfunction, special populations ,Cardiovascular Diseases ,Heart failure ,Asymptomatic Diseases ,Female ,diastolic dysfunction ,centenarians ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background: Population aging has increased together with the need for cardiovascular care. Understanding the relevance of cardiovascular conditions in the very old is crucial to developing a specific and rationale therapeutic approach. Centenarians can be considered a model of successful aging, although the impact of cardiovascular disease in this population is still unclear. Aim: To evaluate the cardiovascular health status of a subset of centenarians enrolled in the Centenari a Trieste study and living in the province of Trieste to describe the prevalence of cardiovascular conditions among them. Methods: The current study included 20 individuals born before 1919 and living in the province of Trieste as of 1 May 2019. All centenarians were able to give consent and were subjected to an in-home complete clinical assessment focused on cardiovascular conditions, ECG and echocardiography. Results: The majority of centenarians were women (85%) and were not taking any chronic cardiovascular medication (55%). No centenarians had a history of ischemic heart disease while about one-third had signs suggestive of heart failure at examination (20%). Atrial fibrillation was present in 20% of individuals and conduction disorders were uncommon. Although the majority of individuals had a preserved left ventricular function, diastolic function was abnormal in 80% of enrolled centenarians that, however, was mild in 73% of cases. Conclusion: This is the second study to perform in-home echocardiography in centenarians and the first to characterize the cardiovascular status of centenarians living in Trieste. The majority of centenarians had asymptomatic diastolic dysfunction and were naïve from cardiovascular therapy. The recruitment of new individuals from the Trieste area is continuing to perform analyses on clinical, genetic and environmental factors that may predict greater longevity in this geographical context and unveil mechanisms that regulate cardiac aging associated with increased lifespan.
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- 2020
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36. Colchicine in Athero-Thrombosis: Molecular Mechanisms and Clinical Evidence
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Giovanni Cimmino, Francesco S. Loffredo, Gennaro De Rosa, Plinio Cirillo, Cimmino, G., Loffredo, F. S., De Rosa, G., Cirillo, P., Cimmino, Giovanni, Loffredo, Francesco S, De Rosa, Gennaro, and Cirillo, Plinio
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Inorganic Chemistry ,cardiovascular disease ,inflammation ,Organic Chemistry ,General Medicine ,Physical and Theoretical Chemistry ,Molecular Biology ,Spectroscopy ,Catalysis ,colchicine ,Computer Science Applications - Abstract
Several lines of evidence have clearly indicated that inflammation plays a pivotal role in the development of atherosclerosis and of its thrombotic complications such as acute coronary syndromes or ischemic stroke. Thus, it has been postulated that the use of anti-inflammatory agents might be extremely useful to improve cardiovascular outcome. Recently, increasing attention has been reserved to one of the oldest plant-derived drugs still in use in clinical practice, colchicine that has been used as drug to treat inflammatory diseases such gout or Mediterranean fever. To date, current guidelines of the European Society of Cardiology have included colchicine as first line choice for treatment of acute and recurrent pericarditis. Moreover, several studies have investigated its role in the clinical scenarios of cardiovascular disease including chronic and acute coronary syndromes with promising results. In this review, starting from a description of the mechanism(s) involved behind its anti-inflammatory effects, we give an overview on its potential effects in atherothrombosis and finally present an updated overview of clinical evidence on the role of this drug in cardiovascular disease.
- Published
- 2023
37. Exploiting AT2R to Improve CD117 Stem Cell Function In Vitro and In Vivo - Perspectives for Cardiac Stem Cell Therapy.
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Ludwig, Marion, Tölk, Anita, Skorska, Anna, Maschmeier, Christian, Gaebel, Ralf, Lux, Cornelia Aquilina, Steinhoff, Gustav, and David, Robert
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C-kit protein ,STEM cell treatment ,IN vitro studies ,HEART diseases ,THERAPEUTICS ,ANGIOTENSIN receptors ,MYOCARDIAL infarction treatment - Abstract
Background/Aims: CD117
+ stem cell (SC) based therapy is considered an alternative therapeutic option for terminal heart disease. However, controversies exist on the effects of CD117+ SC implantation. In particular, the link between CD117+ SC function and angiotensin-II-type-2 receptor (AT2R) after MI is continuously discussed. We therefore asked whether 1) AT2R stimulation influences CD117+ SC properties in vitro and, 2) which effects can be ascribed to AT2R stimulation in vivo. Methods: We approached AT2R stimulation with Angiotensin II while simultaneously blocking its opponent receptor AT1 with Losartan. CD117 effects were dissected using a 2D-Matrigel assay and HL-1 co-culture in vitro. A model of myocardial infarction, in which we implanted EGFP+ CD117 SC, was further applied. Results: While we found indications for AT2R driven vasculogenesis in vitro, co-culture experiments revealed that CD117+ SC improve vitality of cardiomyocytes independently of AT2R function. Likewise, untreated CD117+ SC had a positive effect on cardiac function and acted cardioprotective in vivo. Conclusions: Therefore, our data show that transient AT2R stimulation does not significantly add to the beneficial actions of CD117+ SC in vivo. Yet, exploiting AT2R driven vasculogenis via an optimized AT2R stimulation protocol may become a promising tool for cardiac SC therapy. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]- Published
- 2015
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38. Percutaneous Left Atrial Appendage Occlusion: An Emerging Option in Patients with Atrial Fibrillation at High Risk of Bleeding
- Author
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Dario Prozzo, Paolo Golino, Emanuele Gallinoro, Francesco Loffredo, Luigi Colucci Cante, Maurizio Cappelli Bigazzi, Giovanni Cimmino, Gemma Salerno, Dario Fabiani, Cimmino, Giovanni, Loffredo, Francesco S, Gallinoro, Emanuele, Prozzo, Dario, Fabiani, Dario, Cante, Luigi, Salerno, Gemma, Cappelli Bigazzi, Maurizio, and Golino, Paolo
- Subjects
medicine.medical_specialty ,Medicine (General) ,Percutaneous ,left atrial appendage occlusion ,medicine.medical_treatment ,Population ,Femoral vein ,Ischemia ,Hemorrhage ,Review ,Left atrial appendage occlusion ,R5-920 ,bleeding risk ,Internal medicine ,Atrial Fibrillation ,Medicine ,Humans ,Atrial Appendage ,Embolization ,Thrombus ,education ,education.field_of_study ,business.industry ,Anticoagulant ,Anticoagulants ,Atrial fibrillation ,General Medicine ,cardioembolism ,medicine.disease ,Europe ,Stroke ,Treatment Outcome ,Cardiology ,stroke prevention ,business ,Human - Abstract
Atrial fibrillation (AF) is a common cardiac arrhythmia with an estimated prevalence of 1% in the general population. It is associated with an increased risk of ischemic stroke, silent cerebral ischemia, and cognitive impairment. Due to the blood flow stasis and morphology, thrombus formation occurs mainly in the left atrial appendage (LAA), particularly in the setting of nonvalvular AF (NVAF). Previous studies have shown that >90% of emboli related to NVAF originate from the LAA, thus prevention of systemic cardioembolism is indicated. According to the current guidelines, anticoagulant therapy with direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs), represents the standard of care in AF patients, in order to prevent ischemic stroke and peripheral embolization. Although these drugs are widely used and DOACs have shown, compared to VKAs, non-inferiority for stroke prevention with significantly fewer bleeding complications, some issues remain a matter of debate, including contraindications, side effects, and adherence. An increasing number of patients, indeed, because of high bleeding risk or after experiencing life-threatening bleedings, must take anticoagulants with extreme caution if not contraindicated. While surgical closure or exclusion of LAA has been historically used in patients with AF with contradictory results, in the recent years, a novel procedure has emerged to prevent the cardioembolic stroke in these patients: The percutaneous left atrial appendage occlusion (LAAO). Different devices have been developed in recent years, though not all of them are approved in Europe and some are still under clinical investigation. Currently available devices have shown a significant decrease in bleeding risk while maintaining efficacy in preventing thromboembolism. The procedure can be performed percutaneously through the femoral vein access, under general anesthesia. A transseptal puncture is required to access left atrium and is guided by transesophageal echocardiography (TEE). Evidence from the current literature indicates that percutaneous LAAO represents a safe alternative for those patients with contraindications for long-term oral anticoagulation. This review summarizes scientific evidences regarding LAAO for stroke prevention including clinical indications and an adequate patient selection.
- Published
- 2021
39. Restoring Systemic GDF11 Levels Reverses Age-Related Dysfunction in Mouse Skeletal Muscle.
- Author
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Manisha Sinha, Jang, Young C., Juhyun Oh, Danika Khong, Wu, Elizabeth Y., Manohar, Rohan, Miller, Christine, Regalado, Samuel G., Loffredo, Francesco S., Pancoast, James R., Hirshman, Michael F., Lebowitz, Jessica, Shadrach, Jennifer L., Cerletti, Massimiliano, Mi-Jeong Kim, Serwold, Thomas, Goodyear, Laurie J., Rosner, Bernard, Lee, Richard T., and Wagers, Amy J.
- Subjects
- *
SKELETAL muscle physiology , *PHYSIOLOGICAL aspects of aging , *GROWTH factors , *PARABIOSIS , *SATELLITE cells - Abstract
Parabiosis experiments indicate that impaired regeneration in aged mice is reversible by exposure to a young circulation, suggesting that young blood contains humoral "rejuvenating" factors that can restore regenerative function. Here, we demonstrate that the circulating protein growth differentiation factor 11 (GDF11) is a rejuvenating factor for skeletal muscle. Supplementation of systemic GDF11 levels, which normally decline with age, by heterochronic parabiosis or systemic delivery of recombinant protein, reversed functional impairments and restored genomic integrity in aged muscle stem cells (satellite cells). Increased GDF11 levels in aged mice also improved muscle structural and functional features and increased strength and endurance exercise capacity. These data indicate that GDF11 systemically regulates muscle aging and may be therapeutically useful for reversing age-related skeletal muscle and stem cell dysfunction. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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40. Prostaglandin E2 promotes post-infarction cardiomyocyte replenishment by endogenous stem cells.
- Author
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Hsueh, Ying‐Chang, Wu, Jasmine M F, Yu, Chun‐Keung, Wu, Kenneth K, and Hsieh, Patrick C H
- Abstract
Although self-renewal ability of adult mammalian heart has been reported, few pharmacological treatments are known to promote cardiomyocyte regeneration after injury. In this study, we demonstrate that the critical period of stem/progenitor cell-mediated cardiomyocyte replenishment is initiated within 7 days and saturates on day 10 post-infarction. Moreover, blocking the inflammatory reaction with COX-2 inhibitors may also reduce the capability of endogenous stem/progenitor cells to repopulate lost cells. Injection of the COX-2 product PGE
2 enhances cardiomyocyte replenishment in young mice and recovers cell renewal through attenuating TGF-β1 signaling in aged mice. Further analyses suggest that cardiac stem cells are PGE2 -responsive and that PGE2 may regulate stem cell activity directly through the EP2 receptor or indirectly by modulating its micro-environment in vivo. Our findings provide evidence that PGE2 holds great potential for cardiac regeneration. [ABSTRACT FROM AUTHOR]- Published
- 2014
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41. Human endometrial stem cells confer enhanced myocardial salvage and regeneration by paracrine mechanisms.
- Author
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Jiang, Zhi, Hu, Xinyang, Yu, Hong, Xu, Yinchuan, Wang, Lihan, Chen, Han, Chen, Huiqiang, Wu, Rongrong, Zhang, Zhaocai, Xiang, Chunsheng, Webster, Keith A, and Wang, Jian‐an
- Subjects
HEART failure treatment ,STEM cells ,PARACRINE mechanisms ,CLINICAL trials ,LABORATORY rats ,MYOCARDIAL infarction ,HEART cells - Abstract
Human endometrial stem cells (En SCs) have the potential to be 'off the shelf' clinical reagents for the treatment of heart failure. Here, using an immunocompetent rat model of myocardial infarction ( MI), we provide evidence that the functional benefits of En SC transplantation are principally and possibly exclusively through a paracrine effect. Human En SCs were delivered by intramyocardial injection into rats 30 min. after coronary ligation. En SC therapy significantly preserved viable myocardium in the infarct zone and improved cardiac function at 28 days. Despite increased viable myocardium and vascular density, there was scant evidence of differentiation of En SCs into any cardiovascular cell type. Cultured human En SCs expressed a distinctive profile of cytokines that enhanced the survival, proliferation and function of endothelial cells in vitro. When injected into the peri-infarct zone, human En SCs activated AKT, ERK1/2 and STAT3 and inhibited the p38 signalling pathway. En SC therapy decreased apoptosis and promoted cell proliferation and c-kit+ cell recruitment in vivo. Myocardial protection and enhanced post-infarction regeneration by En SCs is mediated primarily by paracrine effects conferred by secreted cytokines that activate survival pathways and recruit endogenous progenitor stem cells. Menstrual blood provides a potentially limitless source of biologically competent 'off the shelf' En SCs for allogeneic myocardial regenerative medicine. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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42. Colchicine reduces platelet aggregation by modulating cytoskeleton rearrangement via inhibition of cofilin and LIM domain kinase 1
- Author
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Bruno Trimarco, Gaetano Calì, Roberta Tarallo, Grazia Pellegrino, Stefano Conte, Francesco S. Loffredo, Plinio Cirillo, Andrea Morello, Giovanni Cimmino, Paolo Golino, Nicola De Luca, Cimmino, Giovanni, Tarallo, Roberta, Conte, Stefano, Morello, Andrea, Pellegrino, Grazia, Loffredo, Francesco S., Calì, Gaetano, De Luca, Nicola, Golino, Paolo, Trimarco, Bruno, Cirillo, Plinio, and Loffredo, Francesco
- Subjects
Platelets ,Blood Platelets ,0301 basic medicine ,Cofilin 1 ,Platelet Aggregation ,Lim Kinase ,Physiology ,Protein subunit ,Protein Kinase Inhibitor ,macromolecular substances ,030204 cardiovascular system & hematology ,LIMK1 ,03 medical and health sciences ,chemistry.chemical_compound ,Myosin-Light-Chain Phosphatase ,Cytoskeleton Colchicine Platelets ,0302 clinical medicine ,Microtubule ,Humans ,Platelet activation ,Phosphorylation ,Cytoskeleton ,Protein Kinase Inhibitors ,Pharmacology ,biology ,Platelet Aggregation Inhibitor ,Platelet ,Lim Kinases ,Colchicine ,Cofilin ,Cell biology ,Adenosine diphosphate ,030104 developmental biology ,Tubulin ,chemistry ,biology.protein ,Blood Platelet ,Molecular Medicine ,Platelet Aggregation Inhibitors ,Human ,Signal Transduction - Abstract
Introduction Platelets activation/aggregation with subsequent thrombus formation is the main event in the pathophysiology of acute coronary syndrome. Once activated, platelets show an extensive cytoskeleton rearrangement that leads to recruitment of additional platelets to finally cause haemostatic plug formation. Thus, the cytoskeleton plays a pivotal role in this phenomenon. Colchicine (COLC) is an anti-inflammatory drug proven to reduce major cardiovascular events in patients with coronary artery disease. The molecular mechanisms by which COLC exerts these protective effects remain partially still unknown. Since COLC causes disruption of tubulin, a component of cell cytoskeleton, we investigated whether this drug might interfere with platelet aggregation by acting on cytoskeleton rearrangement. Methods and results Platelets isolated from healthy volunteers were activated with Adenosine Diphosphate (ADP, 20 μM) Collagen (COLL, 60 μg/ml) and Thrombin Activating Receptor Peptide (TRAP 25 μM) with/without COLC 10 μM pretreatment. After stimulus, aggregation was measured by light aggregometry overtime. Microtubules structure was assessed by immunohistochemistry and key proteins involved in regulation of actin-filament assembly and contractility such as Myosin Phosphatase Targeting subunit (MYPT), LIM domain kinase 1(LIMK1) and cofilin were evaluated by Western Blot analysis. Colchicine pretreatment significantly blunted ADP/COLL/TRAP-induced platelet aggregation (up to 40%). COLC effects appeared mediated by microtubules depolymerization and cytoskeleton disarrangement associated to inactivation of MYPT and LIMK1 that finally interfered with cofilin activity. Conclusions Our data indicate that colchicine exerts anti-platelet effects in vitro via inhibition of key proteins involved in cytoskeleton rearrangement, suggesting that its beneficial cardiovascular properties may be due, at least in part, to an inhibitory effect of platelet activity.
- Published
- 2018
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43. Role of circulating factors in cardiac aging
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Francesco S. Loffredo, Gabriella Marcon, Giulio Ciucci, Gianfranco Sinagra, Giovanni Cimmino, Luca Camparini, Antonio Cannatà, Cannatà, Antonio, Marcon, Gabriella, Cimmino, Giovanni, Camparini, Luca, Ciucci, Giulio, Sinagra, Gianfranco, Loffredo, Francesco S., and Loffredo, Francesco
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,Aging ,Cardiac aging ,Circulating factors ,Parabiosis ,Circulating factor ,business.industry ,Physiology ,Tissue physiology ,Review Article ,030204 cardiovascular system & hematology ,Bioinformatics ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Life expectancy ,Medicine ,Risk factor ,business ,Organ system ,Parabiosi - Abstract
Worldwide increase in life expectancy is a major contributor to the epidemic of chronic degenerative diseases. Aging, indeed, simultaneously affects multiple organ systems, and it has been hypothesized that systemic alterations in regulators of tissue physiology may regulate this process. Cardiac aging itself is a major risk factor for cardiovascular diseases and, because of the intimate relationship with the brain, may contribute to increase the risk of neurodegenerative disorders. Blood-borne factors may play a major role in this complex and still elusive process. A number of studies, mainly based on the revival of parabiosis, a surgical technique very popular during the 70s of the 20 th century to study the effect of a shared circulation in two animals, have indeed shown the potential that humoral factors can control the aging process in different tissues. In this article we review the role of circulating factors in cardiovascular aging. A better understanding of these mechanisms may provide new insights in the aging process and provide novel therapeutic opportunities for chronic age-related disorders.
- Published
- 2017
44. Immune-inflammatory activation in acute coronary syndromes: A look into the heart of unstable coronary plaque
- Author
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Francesco S. Loffredo, Giovanni Cimmino, Paolo Golino, Saverio D’Elia, Alberto Morello, Plinio Cirillo, Raffaele De Palma, Cimmino, Giovanni, Loffredo, Francesco S, Morello, Alberto, D'Elia, Saverio, De Palma, Raffaele, Cirillo, Plinio, Golino, Paolo, Cimmino, G, Loffredo, F, Morello, A, Elia S, D, De Palma, R, and Golino, P.
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,Inflammation ,030204 cardiovascular system & hematology ,medicine.disease_cause ,Article ,Lesion ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,medicine ,Thrombus ,Coagulation ,business.industry ,Immunity ,Thrombosis ,General Medicine ,medicine.disease ,Atherosclerosis ,Vulnerable plaque ,Pathophysiology ,030104 developmental biology ,Atherosclerosi ,Thrombosi ,Coronary vessel ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
In the last twenty years, our comprehension of the molecular mechanisms involved in formation, progression and complication of atherosclerotic plaque has advanced significantly and the main role of inflammation and immunity in this phenomenon is now largely accepted. Accumulating evidence highlight the crucial role of different inflammatory and immune cells, such as monocytes and T-lymphocytes, in the pathophysiology of atherosclerotic lesion, particularly in contributing to its complications, such as rupture or ulceration. According to the new terminology, "vulnerable plaque" identifies an inflamed atherosclerotic lesion that is particularly prone to rupture. Once disrupted, prothrombotic material is exposed to the flowing blood, thus activating coagulation cascade and platelet aggregation, ultimately leading to acute thrombus formation within the coronary vessel. To date this is the key event underlying the clinical manifestation of acute coronary syndromes (ACS). The degree of vessel occlusion (complete vs. incomplete) and the time of blood flow cessation will define the severity of clinical picture. This phenomenon seems to be the final effect of a complex interaction between different local and systemic factors, involving the degree of inflammation, type of cells infiltration and the rheological characteristics of blood flow at the site of plaque rupture, thrombogenic substrates within the atherosclerotic lesion and different soluble mediators, already present or acutely released in the circulating blood. This article will review currently available data on the pathophysiology of ACS, emphasizing the immunological and inflammatory aspects of vulnerable plaque. We may postulate that intraplaque antigens and local microenvironment will define the immune-inflammatory response and cells phenotype, thus determining the severity of clinical manifestations. In the last twenty years, our comprehension of the molecular mechanisms involved in the formation, progression and complication of atherosclerotic plaque has advanced significantly and the main role of inflammation and immunity in this phenomenon is now largely accepted. Accumulating evidence highlight the crucial role of different inflammatory and immune cells, such as monocytes and T-lymphocytes, in the pathophysiology of atherosclerotic lesion, particularly in contributing to its complications, such as rupture or ulceration. According to the new terminology, “vulnerable plaque” identifies an inflamed atherosclerotic lesion that is particularly prone to rupture. Once disrupted, prothrombotic material is exposed to the flowing blood, thus activating coagulation cascade and platelet aggregation, ultimately leading to acute thrombus formation within the coronary vessel. To date this is the key event underlying the clinical manifestations of acute coronary syndromes (ACS). The degree of vessel occlusion (complete vs. incomplete) and the time of blood flow cessation will define the severity of clinical picture. This phenomenon seems to be the final effect of a complex interaction between different local and systemic factors, involving the degree of inflammation, type of cells infiltration and the rheological characteristics of blood flow at the site of plaque rupture, thrombogenic substrates within the atherosclerotic lesion and different soluble mediators, already present or acutely released in the circulating blood. This article will review currently available data on the pathophysiology of ACS, emphasizing the immunological and inflammatory aspects of vulnerable plaque. We may postulate that intraplaque antigens and local microenvironment will define the immune-inflammatory response and cells phenotype, thus determining the severity of clinical manifestations.
- Published
- 2017
45. Mapping current research and identifying hotspots on mesenchymal stem cells in cardiovascular disease.
- Author
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Chen, Chan, Lou, Yang, Li, Xin-Yi, Lv, Zheng-Tian, Zhang, Lu-Qiu, and Mao, Wei
- Subjects
MESENCHYMAL stem cells ,EXOSOMES ,MEDICAL sciences ,CARDIOVASCULAR diseases ,EXTRACELLULAR vesicles ,CARDIOVASCULAR system ,TISSUE scaffolds - Abstract
Background: Mesenchymal stem cells (MSCs) have important research value and broad application prospects in the cardiovascular disease. This study provides information on the latest progress, evolutionary path, frontier research hotspots, and future research developmental trends in this field. Methods: A knowledge map was generated by CiteSpace and VOSviewer analysis software based on data obtained from the literature on MSCs in the cardiovascular field. Results: The USA and China ranked at the top in terms of the percentage of articles, accounting for 34.306% and 28.550%, respectively. The institution with the highest number of research publications in this field was the University of Miami, followed by the Chinese Academy of Medical Sciences and Harvard University. The research institution with the highest ACI value was Harvard University, followed by the Mayo Clinic and the University of Cincinnati. The top three subjects in terms of the number of published articles were cell biology, cardiovascular system cardiology, and research experimental medicine. The journal with the most publications in this field was Circulation Research, followed by Scientific Reports and Biomaterials. The direction of research on MSCs in the cardiovascular system was divided into four parts: (1) tissue engineering, scaffolds, and extracellular matrix research; (2) cell transplantation, differentiation, proliferation, and signal transduction pathway research; (3) assessment of the efficacy of stem cells from different sources and administration methods in the treatment of acute myocardial infarction, myocardial hypertrophy, and heart failure; and (4) exosomes and extracellular vesicles research. Tissue research is the hotspot and frontier in this field. Conclusion: MSC research has presented a gradual upward trend in the cardiovascular field. Multidisciplinary intersection is a characteristic of this field. Engineering and materials disciplines are particularly valued and have received attention from researchers. The progress in multidisciplinary research will provide motivation and technical support for the development of this field. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
46. Pathways for salvage and protection of the heart under stress: novel routes for cardiac rejuvenation
- Author
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Francesco S. Loffredo, Mauro Giacca, Gianfranco Sinagra, Antonio Cannatà, Luca Camparini, Cannatà, Antonio, Camparini, Luca, Sinagra, Gianfranco, Giacca, Mauro, and Loffredo, Francesco S.
- Subjects
0301 basic medicine ,Gerontology ,Population ageing ,Aging ,Heart Diseases ,Physiology ,media_common.quotation_subject ,Health Status ,Aging hormone ,Longevity ,Caloric restriction ,030204 cardiovascular system & hematology ,Biology ,Bioinformatics ,Mitochondria, Heart ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Stress, Physiological ,Aging hormones ,Cardiac aging ,Cardiac hypertrophy ,Cardiac rejuvenation ,Physiology (medical) ,Animals ,Humans ,Regeneration ,Risk factor ,Rejuvenation ,media_common ,Myocardium ,Age Factors ,World population ,030104 developmental biology ,Pharmacological interventions ,Life expectancy ,Cardiology and Cardiovascular Medicine ,Energy Metabolism - Abstract
The world population is aging, and by 2017, there will be more people over the age of 65 than under age 5, and by 2050, two billion of the estimated nine billion people on Earth will be older than 60. Aging itself is a major cardiovascular risk factor, affecting morbidity and mortality of the aging population. At the same time, aging increases the likelihood of the presence of other risk factors. The aged myocardium is characterized by several structural and functional progressive changes that impair its ability to respond appropriately to stressful conditions. Although some progress to understand the complex mechanisms that underlie these phenotypic changes, the molecular pathways that determine the balance between aging and rejuvenation in the aged myocardium still remain elusive. In this article, we review molecular mechanisms responsible for the phenotypic changes observed with aging in the heart, providing insight into molecular pathways and pharmacological interventions that may rejuvenate the aged myocardium. A better understanding of these pathways is essential for determining their therapeutic potential in humans, improving the possibility that the increase in life expectancy that we are observing will be accompanied by a parallel increase in healthspan.
- Published
- 2016
47. Evolving Concepts in LDL-Lowering Strategies: Are We There?
- Author
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Francesco Loffredo, Giovanni Cimmino, Paolo Golino, Giulia Arena, Cimmino, Giovanni, Loffredo, Francesco S, Arena, Giulia, and Golino, Paolo
- Subjects
Statin ,business.industry ,medicine.drug_class ,PCSK9 ,Disease ,Familial hypercholesterolemia ,030204 cardiovascular system & hematology ,Pharmacology ,Bioinformatics ,Proprotein convertase ,medicine.disease ,Cardiovascular risk ,03 medical and health sciences ,0302 clinical medicine ,LDL receptor ,Medicine ,Kexin ,lipids (amino acids, peptides, and proteins) ,030212 general & internal medicine ,Cardiology and Cardiovascular Medicine ,Receptor ,business ,Lipoprotein - Abstract
High plasma levels of low density lipoproteins (LDLs) represent one of the major risk factors for cardiovascular disease, as shown by many epidemiological studies. On the other hand, randomized trials designed to address the clinical impact of lipid lowering interventions, have clearly shown that reduction in LDL plasma levels lead to a significant decrease in major cardiovascular events. Based on these observations, pharmacological modulation of LDLs has been highly investigated. Statins, alone or in combination, represent the most powerful agents to date available to reach the LDLs levels suggested by the current guidelines. However, in some patients the recommended LDL reduction is difficult to be achieved because of genetic background (familial hypercholesterolemia), side effects (statin intolerance), or simply because of a non-sufficient response. In the last few years, our understanding of the basic mechanisms involved in the lipoprotein metabolism has progressed significantly. The crucial role of proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged. The main characterized function of PCSK9 relates to the binding to LDL-C receptors (LDLR) in hepatocytes. However, PCSK9 does not interfere with the binding between LDL and its own receptor, but with the ability of the latest to return to the surface of the hepatocyte and bind new LDL molecules. Based on these observations, blocking PCSK-9 may reduce the LDLR clearance, thus increasing the ability of LDLR to remove circulating LDLs. Pharmacological inhibition of this protein has been proposed as new therapeutic approach. The clinical evidence available to date seem to fully support this hypothesis.
- Published
- 2016
48. Circulating Growth Differentiation Factor 11/8 Levels Decline With Age
- Author
-
Jill M. Goldstein, Emilia Gonzalez, Miook Cho, Tommaso Poggioli, Aysu Uygur, Amy J. Wagers, Claudio Macias-Trevino, Francesco S. Loffredo, Ryan G. Walker, Rachel M Tandias, Peiguo Yang, Ana Vujic, Richard T. Lee, James R. Pancoast, Yick W. Fong, Thomas B. Thompson, Poggioli, Tommaso, Vujic, Ana, Yang, Peiguo, MacIas-Trevino, Claudio, Uygur, Aysu, Loffredo, Francesco S., Pancoast, James R., Cho, Miook, Goldstein, Jill, Tandias, Rachel M., Gonzalez, Emilia, Walker, Ryan G., Thompson, Thomas B., Wagers, Amy J., Fong, Yick W., and Lee, Richard T.
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Aging ,Physiology ,SMAD ,Myostatin ,Biology ,Bone morphogenetic protein ,Horse ,03 medical and health sciences ,Gdf11 protein, mouse ,Mice ,0302 clinical medicine ,In vivo ,Internal medicine ,medicine ,Animals ,Horses ,Mice, Knockout ,Sheep ,Animal ,Bone Morphogenetic Protein ,Growth differentiation factor ,transforming growth factor-β ,Biomarker ,Rats ,Growth Differentiation Factors ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,intercellular signaling peptides and protein ,Growth Differentiation Factor ,Mstn protein, mouse ,GDF11 ,Bone Morphogenetic Proteins ,biology.protein ,Rat ,Antibody ,Cardiology and Cardiovascular Medicine ,030217 neurology & neurosurgery ,Biomarkers ,Transforming growth factor - Abstract
Rationale: Growth differentiation factor 11 (GDF11) and GDF8 are members of the transforming growth factor-β superfamily sharing 89% protein sequence homology. We have previously shown that circulating GDF11 levels decrease with age in mice. However, a recent study by Egerman et al reported that GDF11/8 levels increase with age in mouse serum. Objective: Here, we clarify the direction of change of circulating GDF11/8 levels with age and investigate the effects of GDF11 administration on the murine heart. Methods and Results: We validated our previous finding that circulating levels of GDF11/8 decline with age in mice, rats, horses, and sheep. Furthermore, we showed by Western analysis that the apparent age-dependent increase in GDF11 levels, as reported by Egerman et al, is attributable to cross-reactivity of the anti-GDF11 antibody with immunoglobulin, which is known to increase with age. GDF11 administration in mice rapidly activated SMAD2 and SMAD3 signaling in myocardium in vivo and decreased cardiac mass in both young (2-month-old) and old (22-month-old) mice in a dose-dependent manner after only 9 days. Conclusions: Our study confirms an age-dependent decline in serum GDF11/8 levels in multiple mammalian species and that exogenous GDF11 rapidly activates SMAD signaling and reduces cardiomyocyte size. Unraveling the molecular basis for the age-dependent decline in GDF11/8 could yield insight into age-dependent cardiac pathologies.
- Published
- 2015
49. Bone Marrow-Derived Cell Therapy Stimulates Endogenous Cardiomyocyte Progenitors and Promotes Cardiac Repair
- Author
-
Richard T. Lee, Joseph Gannon, Matthew L. Steinhauser, Francesco S. Loffredo, Loffredo, Francesco S., Steinhauser, Matthew L., Gannon, Joseph, and Lee, Richard T.
- Subjects
Green Fluorescent Proteins ,Myocardial Infarction ,030204 cardiovascular system & hematology ,Biology ,Green Fluorescent Protein ,Article ,Cell therapy ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Genetic ,Stem Cell ,Genetics ,Animals ,Myocyte ,Myocytes, Cardiac ,Progenitor cell ,Bone Marrow Transplantation ,030304 developmental biology ,0303 health sciences ,Cell fusion ,Animal ,Stem Cells ,Transdifferentiation ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,Cell Biology ,Bone Marrow-Derived Cell ,Cell biology ,Proto-Oncogene Proteins c-kit ,Mesenchymal Stem Cell ,030220 oncology & carcinogenesis ,Cell Transdifferentiation ,Immunology ,Molecular Medicine ,Myoblasts, Cardiac - Abstract
Summary Cell therapy can improve cardiac function in animals and humans after injury, but the mechanism is unclear. We performed cell therapy experiments in genetically engineered mice that permanently express green fluorescent protein (GFP) only in cardiomyocytes after a pulse of 4-OH-tamoxifen. Myocardial infarction diluted the GFP + cardiomyocyte pool, indicating refreshment by non-GFP + progenitors. Cell therapy with bone marrow-derived c-kit + cells, but not mesenchymal stem cells, further diluted the GFP + pool, consistent with c-kit + cell-mediated augmentation of cardiomyocyte progenitor activity. This effect could not be explained by transdifferentiation to cardiomyocytes by exogenously delivered c-kit + cells or by cell fusion. Therapy with c-kit + cells but not mesenchymal stem cells improved cardiac function. These findings suggest that stimulation of endogenous cardiogenic progenitor activity is a critical mechanism of cardiac cell therapy.
- Published
- 2015
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50. Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors
- Author
-
John W. Chen, Lida Katsimpardi, Christine M. Miller, Amy J. Wagers, Gregory R. Wojtkiewicz, Richard T. Lee, Pamela A. Schein, Nadia K. Litterman, Francesco S. Loffredo, Lee L. Rubin, Katsimpardi, Lida, Litterman, Nadia K., Schein, Pamela A., Miller, Christine M., Loffredo, Francesco S., Wojtkiewicz, Gregory R., Chen, John W., Lee, Richard T., Wagers, Amy J., and Rubin, Lee L.
- Subjects
Male ,Aging ,Endothelium ,Myoblasts, Skeletal ,Neurogenesis ,Central nervous system ,Biology ,Bone morphogenetic protein ,Article ,Cerebral circulation ,Mice ,Cognition ,Neural Stem Cells ,medicine ,Animals ,Regeneration ,Rejuvenation ,Neural Stem Cell ,Muscle, Skeletal ,Multidisciplinary ,Animal ,Bone Morphogenetic Protein ,Brain ,Anatomy ,Recombinant Protein ,Olfactory Bulb ,Neural stem cell ,humanities ,Olfactory bulb ,Growth Differentiation Factors ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Growth Differentiation Factor ,Cerebrovascular Circulation ,Bone Morphogenetic Proteins ,GDF11 ,Neurogenesi ,Endothelium, Vascular ,Neuroscience ,Parabiosi - Abstract
Help the Aged Muscle function declines with age, as does neurogenesis in certain brain regions. Two teams analyzed the effects of heterochronic parabiosis in mice. Sinha et al. (p. 649 ) found that when an aged mouse shares a circulatory system with a youthful mouse, the aged mouse sees improved muscle function, and Katsimpardi et al. (p. 630 ) observed increased generation of olfactory neurons. In both cases, Growth Differentiation Factor 11 appeared to be one of the key components of the young blood.
- Published
- 2014
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