OBJECTIVE: To prevent apoptosis is thought to be promising for myocardial protection in cardiac surgery. Recently, we showed that BH4 domain of Bcl-xL is essential for the prevention of apoptosis, and that BH4 fused to HIV TAT protein (TAT-BH4) prevented apoptotic cell death. Then, we hypothesized TAT-BH4 may attenuate ischemia/reperfusion injury in rat hearts. METHODS: The isolated rat hearts in the TAT-BH4 preconditioning group (BH4 group, n=8) or control group (C group, n=8) were subjected to warm ischemia (37 degrees C) for 30 min followed by 60 min of reperfusion using Langendorff perfusion system. RESULTS: Left ventricular developed pressure and maximum dP/dt after reperfusion were significantly improved in the BH4 group than those in the C group (P<0.01). Recovery of mitochondrial respiration was significantly better in the BH4 group (P<0.05). Moreover, expression of caspase-3 and TUNEL-positive myocardium were decreased in the BH4 group than those in the C group. CONCLUSIONS: These results demonstrated that TAT-BH4 attenuates myocardial ischemia/reperfusion injury through preventing myocardial apoptosis. Thus, TAT-BH4 may be a novel therapeutic agent for myocardial protection in cardiac surgery.
OBJECTIVE: To prevent apoptosis is thought to be promising for myocardial protection in cardiac surgery. Recently, we showed that BH4 domain of Bcl-xL is essential for the prevention of apoptosis, and that BH4 fused to HIV TAT protein (TAT-BH4) prevented apoptotic cell death. Then, we hypothesized TAT-BH4 may attenuate ischemia/reperfusion injury in rat hearts. METHODS: The isolated rat hearts in the TAT-BH4 preconditioning group (BH4 group, n=8) or control group (C group, n=8) were subjected to warm ischemia (37 degrees C) for 30 min followed by 60 min of reperfusion using Langendorff perfusion system. RESULTS:Left ventricular developed pressure and maximum dP/dt after reperfusion were significantly improved in the BH4 group than those in the C group (P<0.01). Recovery of mitochondrial respiration was significantly better in the BH4 group (P<0.05). Moreover, expression of caspase-3 and TUNEL-positive myocardium were decreased in the BH4 group than those in the C group. CONCLUSIONS: These results demonstrated that TAT-BH4 attenuates myocardial ischemia/reperfusion injury through preventing myocardial apoptosis. Thus, TAT-BH4 may be a novel therapeutic agent for myocardial protection in cardiac surgery.
Authors: Massimo Bonora; Mariusz R Wieckowski; David A Sinclair; Guido Kroemer; Paolo Pinton; Lorenzo Galluzzi Journal: Nat Rev Cardiol Date: 2019-01 Impact factor: 32.419
Authors: Akiko Iwata; Vicki Morgan-Stevenson; Barbara Schwartz; Li Liu; Joan Tupper; Xiaodong Zhu; John Harlan; Robert Winn Journal: PLoS One Date: 2010-02-08 Impact factor: 3.240
Authors: Tim Vervliet; Irma Lemmens; Elien Vandermarliere; Elke Decrock; Hristina Ivanova; Giovanni Monaco; Vincenzo Sorrentino; Nael Nadif Kasri; Ludwig Missiaen; Lennart Martens; Humbert De Smedt; Luc Leybaert; Jan B Parys; Jan Tavernier; Geert Bultynck Journal: Sci Rep Date: 2015-04-15 Impact factor: 4.379