Abstract
Background
Molecules mediating exercise-induced physiological cardiac growth may be beneficial to prevent cardiac injury and remodeling. MicroRNA-486 (miR-486) is a muscle-enriched microRNA which was found to be increased in exercised heart. However, the role of miR-486 in exercise-induced cardiac growth is largely unknown.
Purpose
We aimed to study the function of miR-486 in exercise-induced cardiac growth, and to investigate its potential role in protection against cardiac ischemia/reperfusion (I/R) injury.
Methods
Male C57BL/6 adult mice were subjected to 3-week swimming exercise to induce physiological cardiac growth. Knockdown of miR-486 was performed by intramyocardial injection of miR-486 sponge to evaluate the role of miR-486 in exercise-induced cardiac growth. Moreover, intramyocardial injection of miR-486 overexpression lentivirus was performed to investigate whether miR-486 could reduce infarct size in mice suffered from acute I/R injury (30 min ligation and 24 hr reperfusion of left anterior descending coronary artery). Meanwhile, the functional role of miR-486 was evaluated in neonatal rat cardiomyocytes (NRCMs) treated with oxygen glucose deprivation/reperfusion (OGDR) using Tunel staining. Finally, function-rescue assays were performed to identify target genes of miR-486.
Results
Exercise significantly upregulated miR-486 in the heart, which was reduced by intramyocardial injection of miR-486 sponge. Exercise induced-cardiac growth was abolished in mice with intramyocardial injection of miR-486 sponge, as evidenced by reduced heart weight/body weight ratio and heart weight/tibia length ratio compared to control exercised-mice, suggesting a potential role of miR-486 in mediating exercise-induced cardiac growth. Meanwhile, we found that intramyocardial injection of miR-486 overexpression lentivirus was able to reduce the infarct size as determined by TTC staining. Moreover, in OGDR-induced apoptosis of NRCMs, miR-486 mimics was able to reduce cardiomyocyte apoptosis, while miR-486 inhibitor performed the opposite. Finally, PTEN and FoxO1 were identified as target genes of miR-486 in the control of cardiomyocyte apoptosis.
Conclusions
miR-486 mediates exercise-induced cardiac growth and protects against cardiac I/R injury. Increasing miR-486 might serve as a potential target to reduce myocardial apoptosis upon I/R injury.
Acknowledgement/Funding
This work was supported by the grants from National Natural Science Foundation of China 81722008, 91639101 and 81570362 to JJ Xiao, 81770401 to Y Bei
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