DIPEPTIDYL PEPTIDASE-4 INHIBITOR ATTENUATED ISCHEMIA-REPERFUSION INJURY VIA PREVENTING MITOCHONDRIAL...
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Acute Coronary Syndromes E220 JACC March 12, 2013 Volume 61, Issue 10 DIPEPTIDYL PEPTIDASE-4 INHIBITOR ATTENUATED ISCHEMIA-REPERFUSION INJURY VIA PREVENTING MITOCHONDRIAL DYSFUNCTION AND REDUCING CELLULAR APOPTOSIS Poster Contributions Poster Sessions, Expo North Monday, March 11, 2013, 9:45 a.m.-10:30 a.m. Session Title: ACS Therapy: Basic and Translational Abstract Category: 3. Acute Coronary Syndromes: Therapy Presentation Number: 1301-186 Authors: Kroekkiat Chinda, Siriporn Chattipakorn, Nipon Chattipakorn, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Background: Dipeptidyl peptidase (DPP)-4 inhibitor exerts cardioprotective effects. However, its benefits during cardiac ischemia-reperfusion (IR) injury are not clear. We hypothesized that 1) DPP-4 inhibitor reduces fatal arrhythmias, cardiac dysfunction, and infarct size during IR, and 2) this cardioprotection is via attenuating cardiac mitochondrial dysfunction and cellular apoptosis. Methods: Rats were randomized to receive either DPP-4 inhibitor (vildagliptin, Vil) 2.0 mg/kg or normal saline solution (NSS) intravenously (n=5/ group) prior to a 30-min left anterior descending coronary artery occlusion, followed by a 120-min reperfusion. Arrhythmia scores, cardiac functions, and the infarct size were evaluated. Cardiac tissues were harvested for mitochondria and immunoblot study. Results: Compared to control, DPP-4 inhibitor significantly reduced infarct size (44% reduction, Figure) and preserved systolic function, while arrhythmia scores were not different. Vildagliptin significantly increased Bcl-2 and pro-caspase3 expression, whereas p-connexin43/total connexin43 ratio was not different. In cardiac mitochondria, DPP-4 inhibitor significantly reduced the reactive oxygen species (ROS) production, mitochondrial swelling, and mitochondrial depolarization (Figure). Conclusions: DPP-4 inhibitor provides cardioprotection during IR by reducing infarct size and improving systolic dysfunction by attenuating cardiac mitochondrial dysfunction and apoptosis.
Transcript of DIPEPTIDYL PEPTIDASE-4 INHIBITOR ATTENUATED ISCHEMIA-REPERFUSION INJURY VIA PREVENTING MITOCHONDRIAL...
Acute Coronary Syndromes
E220JACC March 12, 2013Volume 61, Issue 10
dipepTidyl pepTidase-4 inhiBiTor aTTenuaTed ischemia-reperfusion injury via prevenTing miTochondrial dysfuncTion and reducing cellular apopTosis
Poster ContributionsPoster Sessions, Expo NorthMonday, March 11, 2013, 9:45 a.m.-10:30 a.m.
Session Title: ACS Therapy: Basic and TranslationalAbstract Category: 3. Acute Coronary Syndromes: TherapyPresentation Number: 1301-186
Authors: Kroekkiat Chinda, Siriporn Chattipakorn, Nipon Chattipakorn, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Background: Dipeptidyl peptidase (DPP)-4 inhibitor exerts cardioprotective effects. However, its benefits during cardiac ischemia-reperfusion (IR) injury are not clear. We hypothesized that 1) DPP-4 inhibitor reduces fatal arrhythmias, cardiac dysfunction, and infarct size during IR, and 2) this cardioprotection is via attenuating cardiac mitochondrial dysfunction and cellular apoptosis.
methods: Rats were randomized to receive either DPP-4 inhibitor (vildagliptin, Vil) 2.0 mg/kg or normal saline solution (NSS) intravenously (n=5/group) prior to a 30-min left anterior descending coronary artery occlusion, followed by a 120-min reperfusion. Arrhythmia scores, cardiac functions, and the infarct size were evaluated. Cardiac tissues were harvested for mitochondria and immunoblot study.
results: Compared to control, DPP-4 inhibitor significantly reduced infarct size (44% reduction, Figure) and preserved systolic function, while arrhythmia scores were not different. Vildagliptin significantly increased Bcl-2 and pro-caspase3 expression, whereas p-connexin43/total connexin43 ratio was not different. In cardiac mitochondria, DPP-4 inhibitor significantly reduced the reactive oxygen species (ROS) production, mitochondrial swelling, and mitochondrial depolarization (Figure).
conclusions: DPP-4 inhibitor provides cardioprotection during IR by reducing infarct size and improving systolic dysfunction by attenuating cardiac mitochondrial dysfunction and apoptosis.
