title: Repeated remote ischemic conditioning attenuates left ventricular remodeling via exosome-mediated intercellular communication on chronic heart failure after myocardial infarction.
abstract: BACKGROUND
  Remote ischemic conditioning (RIC) by repeated treatment of transient limb ischemia is a clinically applicable method for protecting the heart against injury at the time of reperfusion. In this study, we investigated the effects of repeated RIC on cardiac dysfunction after myocardial infarction (MI).
  
  
  RESULTS
  At 4weeks after MI, rats were separated into the untreated (UT) group or the RIC-treated group. RIC treatment was performed by 5cycles of 5min of bilateral hindlimb ischemia and 5min of reperfusion once a day for 4weeks. Despite comparable MI size, left ventricular (LV) ejection fraction (LVEF) was significantly improved in the RIC group compared with the UT group. Furthermore, the LVEF in the RIC group was improved, although not significantly, after treatment. RIC treatment also prevented the deterioration of LV diastolic function. MI-induced LV interstitial fibrosis in the boundary region and oxidant stress were significantly attenuated by RIC treatment. MicroRNA-29a (miR-29a), a key regulator of tissue fibrosis, was highly expressed in the exosomes and the marginal area of the RIC group. Even in the differentiated C2C12-derived exosomes, miR-29a expression was significantly increased under hypoxic condition. As well as miR-29a, insulin-like growth factor 1 receptor (IGF-1R) was highly expressed both in the exosomes and remote non-infarcted myocardium of the RIC group. IGF-1R expression was also increased in the C2C12-derived exosomes under hypoxic conditions.
  
  
  CONCLUSIONS
  Repeated RIC reduces adverse LV remodeling and oxidative stress by MI. Exosome-mediated intercellular communication may contribute to the beneficial effect of RIC treatment.
authors.affiliation: Department of Cardiovascular Medicine, Osaka City University Medical School, Osaka, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Department of Pharmacology, Osaka City University Medical School, Osaka, Japan. Electronic address: izumi@msic.med.osaka-cu.ac.jp.
authors.forename: Yasukatsu
authors.initials: Y
authors.lastname: Izumi
authors.affiliation: Department of Cardiovascular Medicine, Osaka City University Medical School, Osaka, Japan; Department of Cardiology, Izumi Municipal Hospital, Izumi, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Cardiovascular Medicine, Osaka City University Medical School, Osaka, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Yamazaki
authors.affiliation: Department of Pharmacology, Osaka City University Medical School, Osaka, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shiota
authors.affiliation: Department of Cardiovascular Medicine, Osaka City University Medical School, Osaka, Japan.
authors.forename: Soichi
authors.initials: S
authors.lastname: Sano
authors.affiliation: Department of Pharmacology, Osaka City University Medical School, Osaka, Japan; Applied Pharmacology and Therapeutics, Osaka City University Medical School, Osaka, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Food Hygiene and Environmental Health Division of Applied Life Science, Kyoto Prefectural University, Kyoto, Japan.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Osada-Oka
authors.affiliation: Department of Cardiovascular Medicine, Osaka City University Medical School, Osaka, Japan.
authors.forename: Kenei
authors.initials: K
authors.lastname: Shimada
authors.affiliation: Department of Pharmacology, Osaka City University Medical School, Osaka, Japan; Applied Pharmacology and Therapeutics, Osaka City University Medical School, Osaka, Japan.
authors.forename: Katuyuki
authors.initials: K
authors.lastname: Miura
authors.affiliation: Department of Cardiovascular Medicine, Osaka City University Medical School, Osaka, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshiyama
authors.affiliation: Department of Pharmacology, Osaka City University Medical School, Osaka, Japan; Department of Education, Shitennoji University, Habikino, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwao
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D002908:Chronic Disease; D055354:Exosomes / Q000502:physiology*; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D006614:Hindlimb / Q000098:blood supply; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D016277:Ventricular Function, Left / Q000502:physiology; D020257:Ventricular Remodeling / Q000502:physiology*
keywords: Exosomes; Left ventricular dysfunction; MicroRNA; Myocardial infarction; Remote ischemic conditioning