Inhibition of microRNA‐143‐3p attenuates myocardial hypertrophy by inhibiting inflammatory response

• Published in: Cell biology international Vol. 42; no. 11; pp. 1584 - 1593
• Main Authors: Yu, Bo, Zhao, Yanan, Zhang, Hongli, Xie, Di, Nie, Wei, Shi, Kaiyao
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.11.2018
• Subjects: Animals; Aorta; Aorta - pathology; Aorta - physiopathology; Aorta - surgery; Apoptosis - drug effects; Base Sequence; Body Weight; Cardiovascular diseases; Cell Survival - drug effects; Constriction, Pathologic; extracellular signal‐regulated protein kinase 5; Hemodynamics - drug effects; Hydrogen peroxide; Hydrogen Peroxide - toxicity; Hypertrophy; Inflammation; Inflammation - pathology; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; miR‐143‐3p; Mitogen-Activated Protein Kinase 7 - metabolism; myocardial hypertrophy; Myocardium - metabolism; Myocardium - pathology; NF-kappa B - metabolism; Organ Size; Oxidative stress; Oxidative Stress - drug effects; Phosphorylation - drug effects; PPAR delta - metabolism; proliferator‐activated receptor δ; Rats, Sprague-Dawley; Signal Transduction; miR-143-3p; proliferator-activated receptor δ; myocardial hypertrophy; extracellular signal-regulated protein kinase 5; inflammation
• ISSN: 1065-6995; 1095-8355
• DOI: 10.1002/cbin.11053

MicroRNA‐143‐3p (miR‐143‐3p) is involved in the initiation of inflammatory response and the progression of cardiovascular diseases. Myocardial hypertrophy is a common symptom in numerous cardiovascular diseases. In the current study, we attempted to demonstrate the role of miR‐143‐3p in the development of myocardial hypertrophy by focusing on its association with inflammation. Myocardial hypertrophy was induced by transverse aortic constriction (TAC) method in vivo and by H2O2 administration in vitro. The expression status of miR‐143‐3p and downstream effectors were detected in animal heart tissues and H9c2 cells. Furthermore, the effect of miR‐143‐3p inhibition on H2O2‐induced changes in ERK5/PPARδ/NF‐κB axis was assessed. TAC induced oxidative stress and inflammation in rat heart tissues, which was associated with the increased expressions of miR‐143‐3p and p‐ERK5. However, the up‐regulated expression of miR‐143‐3p had no effect on the expression of ERK5, which was a direct target of miR‐143‐3p. The results of in vitro assays showed that H2O2 administration increased the levels of miR‐143‐3p and p‐EKR5 and induced the activation of NF‐κB pathway. After the inhibition of miR‐143‐3p, the activation of EKR5 and NF‐κB pathway was suppressed, whereas the expression of PPARδ was up‐regulated. The current study demonstrated that miR‐143‐3p is crucial to the initiation of inflammatory response induced by myocardial hypertrophy. The activation of ERK5 following miR‐143‐3p up‐regulation appears to be a complementary response to induce the subsequent anti‐inflammatory signaling transduction, which needed further exploration.