title: Endurance exercise accelerates myocardial tissue oxygenation recovery and reduces ischemia reperfusion injury in mice.
abstract: Exercise training offers cardioprotection against ischemia and reperfusion (I/R) injury. However, few essential signals have been identified to underscore the protection from injury. In the present study, we hypothesized that exercise-induced acceleration of myocardial tissue oxygenation recovery contributes to this protection. C57BL/6 mice (4 weeks old) were trained on treadmills for 45 min/day at a treading rate of 15 m/min for 8 weeks. At the end of 8-week exercise training, mice underwent 30-min left anterior descending coronary artery occlusion followed by 60-min or 24-h reperfusion. Electron paramagnetic resonance oximetry was performed to measure myocardial tissue oxygenation. Western immunoblotting analyses, gene transfection, and myography were examined. The oximetry study demonstrated that exercise markedly shortened myocardial tissue oxygenation recovery time following reperfusion. Exercise training up-regulated Kir6.1 protein expression (a subunit of ATP-sensitive K(+)channel on vascular smooth muscle cells, VSMC sarc-K(ATP)) and protected the heart from I/R injury. In vivo gene transfer of dominant negative Kir6.1AAA prolonged the recovery time and enlarged infarct size. In addition, transfection of Kir6.1AAA increased the stiffness and reduced the relaxation capacity in the vasculature. Together, our study demonstrated that exercise training up-regulated Kir6.1, improved tissue oxygenation recovery, and protected the heart against I/R injury. This exercise-induced cardioprotective mechanism may provide a potential therapeutic intervention targeting VSMC sarc-K(ATP) channels and reperfusion recovery.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Yuanjing
authors.initials: Y
authors.lastname: Li
authors.affiliation: Endocrinology and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Cai
authors.affiliation: School of Pharmacy, University of Wyoming, Laramie, Wyoming, United States of America; Department of Pharmacology, Soochow University, Soochow, Jiangsu, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Cao
authors.affiliation: School of Pharmacy, University of Wyoming, Laramie, Wyoming, United States of America; Department of Cardiology, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Xing
authors.initials: X
authors.lastname: Qin
authors.affiliation: School of Pharmacy, University of Wyoming, Laramie, Wyoming, United States of America.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Zheng
authors.affiliation: Division of Environmental Health Sciences, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Xu
authors.affiliation: School of Pharmacy, University of Wyoming, Laramie, Wyoming, United States of America.
authors.forename: Taylor M
authors.initials: TM
authors.lastname: Sandvick
authors.affiliation: Department of Physiology, University of Arizona, Tucson, Arizona, United States of America.
authors.forename: Kirk
authors.initials: K
authors.lastname: Hutchinson
authors.affiliation: Department of Physiology and Cell Biology, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Loren E
authors.initials: LE
authors.lastname: Wold
authors.affiliation: Division of Pharmacology, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Keli
authors.initials: K
authors.lastname: Hu
authors.affiliation: Division of Environmental Health Sciences, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Kinesiology & Health, University of Wyoming, Laramie, Wyoming, United States of America.
authors.forename: D Paul
authors.initials: DP
authors.lastname: Thomas
authors.affiliation: School of Pharmacy, University of Wyoming, Laramie, Wyoming, United States of America.
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
authors.affiliation: School of Pharmacy, University of Wyoming, Laramie, Wyoming, United States of America.
authors.forename: Guanglong
authors.initials: G
authors.lastname: He
mesh_terms: D000818:Animals; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D054086:KATP Channels / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D009203:Myocardial Infarction / Q000503:physiopathology* / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010101:Oxygen Consumption / Q000235:genetics / Q000502:physiology; D010805:Physical Conditioning, Animal
chemical_list: D054086:KATP Channels; C092520:uK-ATP-1 potassium channel