TY - JOUR
T1 - Repeated remote ischemic conditioning attenuates left ventricular remodeling via exosome-mediated intercellular communication on chronic heart failure after myocardial infarction
AU - Yamaguchi, Takehiro
AU - Izumi, Yasukatsu
AU - Nakamura, Yasuhiro
AU - Yamazaki, Takanori
AU - Shiota, Masayuki
AU - Sano, Soichi
AU - Tanaka, Masako
AU - Osada-Oka, Mayuko
AU - Shimada, Kenei
AU - Miura, Katuyuki
AU - Yoshiyama, Minoru
AU - Iwao, Hiroshi
N1 - Funding Information:
This study was supported in part by Grant-in-Aid for Scientific Research ( 24591101 , 26460344 and 26461081 ) from the Ministry of Education, Culture, Sports, Science, and Technology , and Hoansha Foundation .
Publisher Copyright:
© 2014 Elsevier Ireland Ltd. All rights reserved.
PY - 2015/1/15
Y1 - 2015/1/15
N2 - 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).Methods and results At 4 weeks after MI, rats were separated into the untreated (UT) group or the RIC-treated group. RIC treatment was performed by 5 cycles of 5 min of bilateral hindlimb ischemia and 5 min of reperfusion once a day for 4 weeks. 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.
AB - 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).Methods and results At 4 weeks after MI, rats were separated into the untreated (UT) group or the RIC-treated group. RIC treatment was performed by 5 cycles of 5 min of bilateral hindlimb ischemia and 5 min of reperfusion once a day for 4 weeks. 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.
KW - Exosomes
KW - Left ventricular dysfunction
KW - MicroRNA
KW - Myocardial infarction
KW - Remote ischemic conditioning
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U2 - 10.1016/j.ijcard.2014.10.144
DO - 10.1016/j.ijcard.2014.10.144
M3 - Article
C2 - 25464262
AN - SCOPUS:84916244320
SN - 0167-5273
VL - 178
SP - 239
EP - 246
JO - International Journal of Cardiology
JF - International Journal of Cardiology
ER -