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Nigro P.,Centro Cardiologico Monzino IRCCS | Pompilio G.,Centro Cardiologico Monzino IRCCS | Capogrossi M.C.,Laboratorio Of Patologia Vascolare
Cell Death and Disease | Year: 2013

Cyclophilin A (CyPA) is a ubiquitously distributed protein belonging to the immunophilin family. CyPA has peptidyl prolyl cis-trans isomerase (PPIase) activity, which regulates protein folding and trafficking. Although CyPA was initially believed to function primarily as an intracellular protein, recent studies have revealed that it can be secreted by cells in response to inflammatory stimuli. Current research in animal models and humans has provided compelling evidences supporting the critical function of CyPA in several human diseases. This review discusses recently available data about CyPA in cardiovascular diseases, viral infections, neurodegeneration, cancer, rheumatoid arthritis, sepsis, asthma, periodontitis and aging. It is believed that further elucidations of the role of CyPA will provide a better understanding of the molecular mechanisms underlying these diseases and will help develop novel pharmacological therapies. © 2013 Macmillan Publishers Limited. All rights reserved. Source

Limana F.,Centro Cardiologico Monzino | Capogrossi M.C.,Laboratorio Of Patologia Vascolare | Germani A.,Fondazione Livio Patrizi
Pharmacology and Therapeutics | Year: 2011

During heart development, the epicardium provides cardiogenic progenitor cells and, together with the myocardium, directs lineage specification and coordinates both myocardial growth and coronary vasculature formation. In the adult heart, the established function of the epicardium is to provide a smooth surface that, together with the pericardium, favors heart movement during contraction and relaxation. Recently, epicardial precursor cells with the ability to differentiate into cardiomyocytes and vascular cells have been identified and the quiescent nature of the adult epicardium has been questioned. Interestingly, the signaling pathways involved in this process appear to be regulated, in the adult heart, by mechanisms similar to those in the embryonic heart. This review will summarize the properties of the embryonic epicardium and will focus on recent advances on the role of the adult epicardium in cardiac regeneration. Specifically, we will present aspects of epicardial cell biology that may be relevant to the development of new therapeutic approaches aimed at inducing heart repair following injury. © 2010 Elsevier Inc. All rights reserved. Source

Lauri A.,Centro Cardiologico Monzino CCM | Pompilio G.,Centro Cardiologico Monzino CCM | Capogrossi M.C.,Laboratorio Of Patologia Vascolare
Ageing Research Reviews | Year: 2014

Aging is characterized by a progressive decline in organism functions due to the impairment of all organs. The deterioration of both proliferative tissues in liver, skin and the vascular system, as well as of largely post-mitotic organs, such as the heart and brain could be attributed at least in part to cell senescence.In this review we examine the role of mitochondrial dysfunction and mtDNA mutations in cell aging and senescence. Specifically, we address how p53 and telomerase reverse transcriptase (TERT) activity switch their roles from cytoprotective to detrimental and also examine the role of microRNAs in cell aging. The proposed role of Reactive Oxygen Species (ROS), both as mutating agents and as signalling molecules, underlying these processes is also described. © 2014 Elsevier B.V. Source

D'Alessandra Y.,Centro Cardiologico Monzino IRCCS | Pompilio G.,Centro Cardiologico Monzino IRCCS | Pompilio G.,University of Milan | Capogrossi M.C.,Laboratorio Of Patologia Vascolare
Current Opinion in Cardiology | Year: 2012

Purpose of Review: We will review the role of microRNAs (miRNAs), small noncoding RNAs with regulatory function, in myocardial infarction (MI). Specifically, we will examine the effect of MI on miRNAs' expression in the heart, the effect of MI on circulating miRNAs, which miRNAs' overexpression or downmodulation appears to have a therapeutic role in MI and which cardiac miRNAs are modulated by drugs/experimental molecules/cell transplantation strategies which have an established or potential therapeutic role in MI. Recent Findings: A rapidly increasing number of studies are showing that cardiac and circulating miRNAs are markedly altered in MI. These novel findings shed new light on the mechanisms that lead to MI complications, post-MI ventricular remodeling and cardiac repair. Further, recent studies show that circulating miRNAs may represent novel and sensitive biomarkers of MI and, possibly, also an intercellular signaling mechanism. Overexpression and downregulation of specific miRNAs are being evaluated as a novel approach to the treatment of MI. Finally, it appears that some established and potential MI therapies (approved drugs/experimental molecules/cell therapy interventions) may act, at least in part, via modulation of specific miRNAs. Summary: Although miRNAs' role in MI is still largely uncharacterized, recent studies suggest that miRNAs may represent novel therapeutic targets and MI biomarkers. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

Cencioni C.,Centro Cardiologico Monzino IRCCS | Capogrossi M.C.,Laboratorio Of Patologia Vascolare | Napolitano M.,Laboratorio Of Patologia Vascolare
Cardiovascular Research | Year: 2012

We review the pivotal role of the stromal derived factor (SDF)-1 chemokine in tissue ischaemia and how it orchestrates the rapid revascularization of injured, ischaemic, and regenerating tissues via the CXC chemokine receptors CXCR4 and CXCR7. Furthermore, we discuss the effects of preconditioning (PC), which is a well-known protective phenomenon for tissue ischaemia. The positive effect of both hypoxic and acidic PC on progenitor cell therapeutic potential is reviewed, while stressing the role of the SDF-1/CXCR4 axis in this process. © 2012 The Author. Source

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