Abstract
In the last twenty years, numerous reports provided solid evidence on the involvement of the mitochondrial permeability transition pore (PTP) in myocardial injury caused by ischemia and reperfusion. Indeed, significant cardioprotection is obtained by reducing the open probability of the PTP. This goal has been achieved by pharmacological and genetic interventions aimed at inhibiting cyclophilin D (CyPD), a regulatory protein that favors PTP opening. On the other hand, CyPD inhibition or deletion has been shown to worsen remodeling of the hypertrophic heart, an adverse outcome that must find an explanation within PTP modulation by CyPD. In this review, recent advancements in defining the molecular identity of the PTP are analyzed in relation to its pathophysiological functions and pharmacological modulation. In this respect, advantages and limitations of compounds targeting CyPD are discussed with the analysis of novel PTP inhibitors that do not interact with CyPD.
Keywords: Permeability transition, cyclophilin D, reactive oxygen species, calcium, ischemia, heart.
Current Medicinal Chemistry
Title:Modulation of Mitochondrial Permeability Transition in Ischemia-Reperfusion Injury of the Heart. Advantages and Limitations
Volume: 22 Issue: 20
Author(s): Fabio Di Lisa and Paolo Bernardi
Affiliation:
Keywords: Permeability transition, cyclophilin D, reactive oxygen species, calcium, ischemia, heart.
Abstract: In the last twenty years, numerous reports provided solid evidence on the involvement of the mitochondrial permeability transition pore (PTP) in myocardial injury caused by ischemia and reperfusion. Indeed, significant cardioprotection is obtained by reducing the open probability of the PTP. This goal has been achieved by pharmacological and genetic interventions aimed at inhibiting cyclophilin D (CyPD), a regulatory protein that favors PTP opening. On the other hand, CyPD inhibition or deletion has been shown to worsen remodeling of the hypertrophic heart, an adverse outcome that must find an explanation within PTP modulation by CyPD. In this review, recent advancements in defining the molecular identity of the PTP are analyzed in relation to its pathophysiological functions and pharmacological modulation. In this respect, advantages and limitations of compounds targeting CyPD are discussed with the analysis of novel PTP inhibitors that do not interact with CyPD.
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Lisa Di Fabio and Bernardi Paolo, Modulation of Mitochondrial Permeability Transition in Ischemia-Reperfusion Injury of the Heart. Advantages and Limitations, Current Medicinal Chemistry 2015; 22 (20) . https://dx.doi.org/10.2174/0929867322666150530210005
DOI https://dx.doi.org/10.2174/0929867322666150530210005 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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