MiR-451 antagonist protects against cardiac fibrosis in streptozotocin-induced diabetic mouse heart

Publication date: Available online 11 March 2019Source: Life SciencesAuthor(s): Cui Liang, Lu Gao, Yuan Liu, Yuzhou Liu, Rui Yao, Yapeng Li, Lili Xiao, Leiming Wu, Binbin Du, Zhen Huang, Yanzhou ZhangAbstractAimsMicroRNAs (miRNAs or miRs) are a large class of small noncoding RNAs. The present study aims to evaluate the effect of miR-451 on cardiac remodeling in diabetic cardiomyopathy.Main methodsMice were injected with streptozotocin (STZ) to induce diabetes. Twelve weeks after final STZ injection, mice were subjected to myocardial injection of adenovirus (Ad)-shmiR-451 to knock down miR-451. Mouse heart endothelial cells (MHECs) were treated with a miR-451 antagomir to inhibit miR451 and were exposed to high glucose.Key findingsSixteen weeks after STZ injection, mice exhibited no significant cardiac hypertrophy but did exhibit serious cardiac fibrosis. MiR-451 knockdown attenuated cardiac fibrosis and improved cardiac function. Moreover, we found that miR-451 knockdown suppressed endothelial-to-mesenchymal transition (EndMT) in diabetic mouse hearts. Hyperglycemia-induced EndMT in MHECs was attenuated by the miR-451 antagomir. Activation of AMPKa1/mTOR was decreased in diabetic mouse heart tissue and hyperglycemia-stimulated MHECs, which was increased following miR-451 knockdown or inhibition. AMPKa1 siRNA abrogated the anti-EndMT effects of miR-451 knockdown in MHECs.SignificancemiR-451 participates in the pathology of diabetic cardiomyopathy via AMPKa1-regulated EndMT in ...
Source: Life Sciences - Category: Biology Source Type: research