Ischemic Postconditioning-Regulated miR-499 Protects the Rat Heart Against Ischemia/Reperfusion Injury by Inhibiting Apoptosis through PDCD4.
BACKGROUND
Here, we determined miR-499 involvement in the protective effect of ischemic postconditioning (IPC) against myocardial ischemia/reperfusion (I/R) injury and identified the underlying mechanisms.


METHODS
To investigate the cardioprotective effect of IPC-induced miR-499, rats were divided into the following five groups: sham, I/R, IPC, IPC + scramble, and IPC + antagomiR-499. Hemodynamic indexes were measured by carotid-artery intubation to assess left ventricular function . Ischemia and infarction areas of rat hearts were determined by Evans blue and triphenyltetrazolium chloride staining, and cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end-labeling assay.


RESULTS
IPC attenuated I/R-induced infarct size of the left ventricle (45.28 ± 5.40% vs. 23.56 ± 6.20%, P < 0.05), myocardial apoptosis, and decreased creatine kinase (1867.31 ± 242.41% vs. 990.21 ± 172.39%, P < 0.05), lactate dehydrogenase (2257.50 ± 305.11% vs. 1289.11 ± 347.28%, P < 0.05), and malondialdehyde levels (7.18 ± 1.63% vs. 4.85 ± 1.52%, P < 0.05). Additionally, left ventricular systolic pressure, +dp/dtmax, and -dp/dtmax were elevated, and left ventricular end diastolic pressure was significantly reduced in the IPC group. Furthermore, IPC-mediated cardiac protection against I/R injury was inhibited in vivo and in vitro by knockdown of cardiac miR-499, suggesting that miR-499 may participate in the protective function of IPC against I/R injury through targeting programmed cell death 4 (PDCD4).


CONCLUSIONS
Our data revealed that IPC-regulated miR-499 plays an important role in IPC-mediated cardiac protection against I/R injury by targeting PDCD4.
Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
Jianbing
J
Zhu
Kang
K
Yao
Qian
Q
Wang
Junjie
J
Guo
Hongtao
H
Shi
Leilei
L
Ma
Haibo
H
Liu
Wei
W
Gao
Yunzeng
Y
Zou
Junbo
J
Ge
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001483:Base Sequence; D019295:Computational Biology; D052279:Creatine Kinase, MB Form / Q000097:blood; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D006439:Hemodynamics; D057775:Ischemic Postconditioning; D007770:L-Lactate Dehydrogenase / Q000235:genetics; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000235:genetics* / Q000473:pathology* / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D013482:Superoxide Dismutase / Q000097:blood; D015854:Up-Regulation / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; C558425:MIRN499 microRNA, rat; D035683:MicroRNAs; C467042:Pdcd4 protein, rat; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D052279:Creatine Kinase, MB Form