Modulation of Mitochondrial Permeability Transition in Ischemia-Reperfusion Injury of the Heart. Advantages and Limitations

Author(s): Fabio Di Lisa , Paolo Bernardi .

Journal Name: Current Medicinal Chemistry

Volume 22 , Issue 20 , 2015

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.

Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 22
ISSUE: 20
Year: 2015
Page: [2480 - 2487]
Pages: 8
DOI: 10.2174/0929867322666150530210005
Price: $58

Article Metrics

PDF: 45
HTML: 4
EPUB: 1
PRC: 1