MiR-181a mediates Ang II-induced myocardial hypertrophy by mediating autophagy. 2017

A-L Li, and J-B Lv, and L Gao
Department of Cardiology, Shandong Shanxian Central Hospital, Shanxian, China. tnhdu290@163.com.

OBJECTIVE To investigate the relationship between miR-181a and cardiac hypertrophy and autophagy in rats with myocardial hypertrophy, and whether miR-181a regulates the autophagy through ATG5, thereby participating in the occurrence and development of myocardial hypertrophy. METHODS The rat model of myocardial hypertrophy was established via the abdominal aortic coarctation. The expression of miR-181a in cardiac tissues was detected via reverse transcription-polymerase chain reaction (RT-PCR). The expressions of autophagy-related proteins, ATG5 and LC3II/LC3I, in cardiac tissues, were detected via Western blotting (WB). After the primary culture of myocardial cells in rats, they were stimulated via Angiotensin II (Ang II) to observe the effects of autophagy inhibitor 3-methyladenine (3-MA) and overexpression of ATG5 on the expression of hypertrophic genes in myocardial cells, respectively. The expressions of autophagy-related proteins ATG5 and LC3II/LC3I were detected via WB, the autophagic rate was observed via flow cytometry and the changes in autophagic vacuoles of myocardial cells were observed using the transmission electron microscope. The changes in mRNA and protein expressions of ATG in myocardial cells were observed after the overexpression of miR-181a or the inhibition of miR-181a activity. The changes in miR-181a and the expression of hypertrophic genes in myocardial cells after Ang II stimulation were observed via RT-PCR. RESULTS In rats with myocardial hypertrophy, the cardiac autophagy was increased and the expression of miR-181a in hypertrophic myocardium was downregulated. 3-MA inhibited the ATG5-induced autophagy and improved the Ang II-induced myocardial hypertrophy, while the overexpression of ATG5 enhanced the myocardial autophagy and the expression of hypertrophic genes. MiR-181a regulated the ATG5-induced myocardial autophagy, and its downregulation mediated the Ang II-induced myocardial hypertrophy. CONCLUSIONS The enhancement of ATG5-induced myocardial autophagy mediates the Ang II-induced myocardial hypertrophy. ATG5 is the target gene of miR-181a, it can regulate the myocardial autophagy via ATG5, thus mediating the Ang II-induced myocardial hypertrophy.

UI MeSH Term Description Entries
D008297 Male Males
D008869 Microtubule-Associated Proteins High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules. Ensconsin,Epithelial MAP, 115 kDa,Epithelial Microtubule-Associate Protein, 115 kDa,MAP4,Microtubule Associated Protein,Microtubule Associated Protein 4,Microtubule Associated Protein 7,Microtubule-Associated Protein,Microtubule-Associated Protein 7,E-MAP-115,MAP1 Microtubule-Associated Protein,MAP2 Microtubule-Associated Protein,MAP3 Microtubule-Associated Protein,Microtubule Associated Proteins,Microtubule-Associated Protein 1,Microtubule-Associated Protein 2,Microtubule-Associated Protein 3,7, Microtubule-Associated Protein,Associated Protein, Microtubule,E MAP 115,Epithelial Microtubule Associate Protein, 115 kDa,MAP1 Microtubule Associated Protein,MAP2 Microtubule Associated Protein,MAP3 Microtubule Associated Protein,Microtubule Associated Protein 1,Microtubule Associated Protein 2,Microtubule Associated Protein 3,Microtubule-Associated Protein, MAP1,Microtubule-Associated Protein, MAP2,Microtubule-Associated Protein, MAP3,Protein 7, Microtubule-Associated,Protein, Microtubule Associated,Protein, Microtubule-Associated
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D006332 Cardiomegaly Enlargement of the HEART, usually indicated by a cardiothoracic ratio above 0.50. Heart enlargement may involve the right, the left, or both HEART VENTRICLES or HEART ATRIA. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (HEART FAILURE) or several forms of CARDIOMYOPATHIES. Cardiac Hypertrophy,Enlarged Heart,Heart Hypertrophy,Heart Enlargement,Cardiac Hypertrophies,Enlargement, Heart,Heart Hypertrophies,Heart, Enlarged,Hypertrophies, Cardiac,Hypertrophies, Heart,Hypertrophy, Cardiac,Hypertrophy, Heart
D000071187 Autophagy-Related Protein 5 An autophagy-related protein that functions in AUTOPHAGOSOME biogenesis. It is conjugated to the ATG12 PROTEIN via a process that is similar to UBIQUITINATION and involves the ATG7 PROTEIN and ATG10 enzyme. The ATG12-ATG5 conjugate acts as an E3 UBIQUITIN LIGASE-like enzyme and is required for the localization of ATG8 PROTEINS to AUTOPHAGOSOME vesicle membranes and modification of membrane lipids. ATG-5 Protein,ATG5 Protein,Apoptosis-Specific Protein,Autophagy Protein-5,Autophagy-Related 5 Protein,ATG 5 Protein,Apoptosis Specific Protein,Autophagy Protein 5,Autophagy Related 5 Protein,Autophagy Related Protein 5
D000225 Adenine A purine base and a fundamental unit of ADENINE NUCLEOTIDES. Vitamin B 4,4, Vitamin B,B 4, Vitamin
D000804 Angiotensin II An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS. Angiotensin II, Ile(5)-,Angiotensin II, Val(5)-,5-L-Isoleucine Angiotensin II,ANG-(1-8)Octapeptide,Angiotensin II, Isoleucine(5)-,Angiotensin II, Valine(5)-,Angiotensin-(1-8) Octapeptide,Isoleucine(5)-Angiotensin,Isoleucyl(5)-Angiotensin II,Valyl(5)-Angiotensin II,5 L Isoleucine Angiotensin II,Angiotensin II, 5-L-Isoleucine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001343 Autophagy The segregation and degradation of various cytoplasmic constituents via engulfment by MULTIVESICULAR BODIES; VACUOLES; or AUTOPHAGOSOMES and their digestion by LYSOSOMES. It plays an important role in BIOLOGICAL METAMORPHOSIS and in the removal of bone by OSTEOCLASTS. Defective autophagy is associated with various diseases, including NEURODEGENERATIVE DISEASES and cancer. Autophagocytosis,ER-Phagy,Lipophagy,Nucleophagy,Reticulophagy,Ribophagy,Autophagy, Cellular,Cellular Autophagy,ER Phagy

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