scholarly journals GW25-e4247 Change and trend of the reperfusion injury salvage kinase and mitochondrial permeability transition pore after ischemic postconditioning in myocardial ischemia-reperfusion in rats

2014 ◽  
Vol 64 (16) ◽  
pp. C67
Author(s):  
Xiao Jun
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Mitochondrial Permeability Transition Pore ◽  
Mitochondrial Permeability Transition ◽  
Ischemia Reperfusion ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Mitochondrial Permeability ◽  
Reperfusion Injury Salvage Kinase ◽  
Myocardial Ischemia Reperfusion

Abstract 16743: A Kinase Interacting Protein 1 Does Not Protect From Adverse Cardiac Remodelling but Attenuates Myocardial Ischemia - Reperfusion Injury

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Harmen G Booij ◽  
Hongjuan Yu ◽  
Rudolf A de Boer ◽  
Wiek H van Gilst ◽  
Herman H Silljé ◽  
...  
Keyword(s):  
Heart Failure ◽  
Mitochondrial Permeability Transition Pore ◽  
Mitochondrial Permeability Transition ◽  
Ischemia Reperfusion ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Wild Type ◽  
Interacting Protein ◽  
Mitochondrial Permeability ◽  
Myocardial Ischemia Reperfusion

Introduction: A kinase interacting protein 1 (AKIP1) attenuates myocardial ischemia / reperfusion (I/R) injury and stimulates beneficial cardiac remodeling in cultured cardiomyocytes. Whether these findings translate into functional benefits in vivo remains to be established. Hypothesis: We assessed the hypothesis that cardiac overexpression of AKIP1 attenuates myocardial heart failure development or I/R-injury in mice. Methods: We created transgenic mice with cardiac-specific overexpression of AKIP1 (AKIP1-TG). First, AKIP1-TG mice or their wild type littermates were subjected to transverse aortic constriction (TAC) and myocardial infarction (MI) with permanent ligation of the left coronary artery. Second, infarct size after 45 minutes ischemia followed by 24h reperfusion was assessed with Evans Bleu and triphenyltetrazolium chloride staining. Results: AKIP1-TG mice and wild type littermates displayed similar left ventricular remodeling and function after TAC or MI as measured with magnetic resonance imaging. Histological indices of heart failure severity, including cardiomyocyte cross-sectional area, capillary density and fibrosis were also similar. However, infarct size relative to the area at risk was reduced 2-fold in AKIP1-TG mice after I/R (15% ± 3 vs. 29± 4 %, p<0,05) and accompanied with a marked reduction in apoptosis (5,4 ± 0,5% vs. 8,1 ± 1,1%, p<0,05). AKIP1 overexpression did not influence cardiac transcription or signaling. Subcellular fraction studies showed enrichment of AKIP1 in mitochondria. In addition, AKIP1 attenuated calcium induced swelling of mitochondria (0.77 ± 0.01 vs. 0.71 ± 0.01, p<0.05), suggesting a direct role for AKIP1 in the mitochondrial permeability transition pore. Conclusions: In conclusion, AKIP1 does not influence cardiac remodeling in models of chronic heart failure. However, AKIP1 does attenuate myocardial I/R injury through stabilization of the mitochondrial permeability transition pore.

Melatonin protects against heart ischemia-reperfusion injury by inhibiting mitochondrial permeability transition pore opening

2009 ◽  
Vol 297 (4) ◽  
pp. H1487-H1493 ◽  
Author(s):  
Giuseppe Petrosillo ◽  
Giuseppe Colantuono ◽  
Nicola Moro ◽  
Francesca M. Ruggiero ◽  
Edy Tiravanti ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Mitochondrial Permeability Transition Pore ◽  
Mitochondrial Permeability Transition ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Cytochrome C Release ◽  
Mitochondrial Permeability ◽  
Mptp Opening

Melatonin, a well-known antioxidant, has been shown to protect against ischemia-reperfusion myocardial damage. Mitochondrial permeability transition pore (MPTP) opening is an important event in cardiomyocyte cell death occurring during ischemia-reperfusion and therefore a possible target for cardioprotection. In the present study, we tested the hypothesis that melatonin could protect heart against ischemia-reperfusion injury by inhibiting MPTP opening. Isolated perfused rat hearts were subjected to global ischemia and reperfusion in the presence or absence of melatonin in a Langerdoff apparatus. Melatonin treatment significantly improves the functional recovery of Langerdoff hearts on reperfusion, reduces the infarct size, and decreases necrotic damage as shown by the reduced release of lactate dehydrogenase. Mitochondria isolated from melatonin-treated hearts are less sensitive than mitochondria from reperfused hearts to MPTP opening as demonstrated by their higher resistance to Ca2+. Similar results were obtained following treatment of ischemic-reperfused rat heart with cyclosporine A, a known inhibitor of MPTP opening. In addition, melatonin prevents mitochondrial NAD+ release and mitochondrial cytochrome c release and, as previously shown, cardiolipin oxidation associated with ischemia-reperfusion. Together, these results demonstrate that melatonin protects heart from reperfusion injury by inhibiting MPTP opening, probably via prevention of cardiolipin peroxidation.

scholarly journals Nanoparticle‐Mediated Simultaneous Targeting of Mitochondrial Injury and Inflammation Attenuates Myocardial Ischemia‐Reperfusion Injury

2021 ◽  
Author(s):  
Gentaro Ikeda ◽  
Tetsuya Matoba ◽  
Ayako Ishikita ◽  
Kazuhiro Nagaoka ◽  
Kaku Nakano ◽  
...  
Keyword(s):  
Chemokine Receptor ◽  
Mitochondrial Permeability Transition Pore ◽  
Mitochondrial Permeability Transition ◽  
Ischemia Reperfusion ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Therapeutic Effects ◽  
Mitochondrial Permeability ◽  
Permeability Transition Pore Opening ◽  
Myocardial Ischemia Reperfusion

Background The opening of mitochondrial permeability transition pore and inflammation cooperatively progress myocardial ischemia‐reperfusion (IR) injury, which hampers therapeutic effects of primary reperfusion therapy for acute myocardial infarction. We examined the therapeutic effects of nanoparticle‐mediated medicine that simultaneously targets mitochondrial permeability transition pore and inflammation during IR injury. Methods and Results We used mice lacking cyclophilin D (CypD, a key molecule for mitochondrial permeability transition pore opening) and C‐C chemokine receptor 2 and found that CypD contributes to the progression of myocardial IR injury at early time point (30–45 minutes) after reperfusion, whereas C‐C chemokine receptor 2 contributes to IR injury at later time point (45–60 minutes) after reperfusion. Double deficiency of CypD and C‐C chemokine receptor 2 enhanced cardioprotection compared with single deficiency regardless of the durations of ischemia. Deletion of C‐C chemokine receptor 2, but not deletion of CypD, decreased the recruitment of Ly‐6C high monocytes after myocardial IR injury. In CypD‐knockout mice, administration of interleukin‐1β blocking antibody reduced the recruitment of these monocytes. Combined administration of polymeric nanoparticles composed of poly‐lactic/glycolic acid and encapsulating nanoparticles containing cyclosporine A or pitavastatin, which inhibit mitochondrial permeability transition pore opening and monocyte‐mediated inflammation, respectively, augmented the cardioprotection as compared with single administration of nanoparticles containing cyclosporine A or pitavastatin after myocardial IR injury. Conclusions Nanoparticle‐mediated simultaneous targeting of mitochondrial injury and inflammation could be a novel therapeutic strategy for the treatment of myocardial IR injury.

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