Attenuation of MicroRNA-495 Derepressed PTEN to Effectively Protect Rat Cardiomyocytes from Hypertrophy

Abstract

Background: The effect of microRNA (miR)-495 on cardiomyocyte hypertrophy was explored by investigating the expression of proteins in the phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway. Methods: The study used a rat model of pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) administration (60 mg/kg) for 2 weeks. Arterial wall thickness and right ventricular hypertrophy were examined by hematoxylin and eosin (HE) staining in the lungs and hearts. The expression level of miR-495 and PTEN was analyzed by quantitative (q)PCR and Western blotting. From the cellular level, we used loss-of-function approaches to investigate the functional roles of miR-495 in cardiac hypertrophy induced by angiotensin II (Ang II) with immunofluorescence, qPCR, and Western blotting. Results: The results showed that upregulation of miR-495 markedly influenced the expression of hypertrophic markers, including the induction of nppa and the inhibition of myh6. In contrast, a reduction in the level of miR-495 attenuated an Ang II-induced hypertrophic reaction. Furthermore, PTEN was identified as a potential target of miR-495 by a bioinformatics algorithm. Luciferase analysis and Western blot analysis confirmed that the contribution of miR-495 to cardiomyocyte hypertrophy may partly be through targeting PTEN. Conclusions: Attenuation of miR-495 derepressed PTEN to effectively protect rat cardiomyocytes from hypertrophy.

Oxidative Stress-Responsive MicroRNAs in Heart Injury

“…Important miRNAs involved in the cardiac hypertrophy are also miRNA-22 (influence phosphatidylinositol-3-kinase (PI3K)-protein kinase B (AKT)) [100], miRNA-212/132 family (active through antihypertrophic FoxO3 transcription factor), or miRNA-199 (miRNA-199a targets the pro-autophagic and antihypertrophic factor glycogen synthase kinase 3β; miRNA-199b acts through targeting tyrosine phosphorylation regulated kinase 1A (Dyrk1a) gene, involved in the phosphorylation of NFAT factors) [101][102][103]. Other studies dealing with miRNAs associated with cardiac hypertrophy observed changed expression of miRNA- 21, -18b, -195, -199, -29, -22, or -23 levels [104-107].…”

The Role of Biomarkers in Cardio-Oncology

“…Non-coding RNAs (microRNAs) mediate cardiac hypertrophy (microRNA-22, microRNA-495 and several more) [ 126 – 128 ] and fibrosis (microRNA-433) [ 129 ], and as such may represent important biomarkers of HF. Also, they can be used to differentiate between reduced and preserved ejection HF, as well as determine prognosis.…”

MicroRNAs in Cardiac Diseases

“…Its cardiac-specific deletion in mouse was sufficient to blunt hypertrophy and cardiac remodeling in the presence of stressors, such as isoproterenol and activated calcineurin transgene [37]. Additionally, miR-22 overexpression in neonatal rat cardiomyocytes increased cell size and induced hypertrophic markers, such as the natriuretic peptide A ( Nppa ) gene, while knockdown of miR-22 attenuated the hypertrophy induced by phenylephrine, isoproterenol or angiotensin II (Ang-II) [45]. The Authors showed that miR-22 might influence CH by Pten inhibition, possibly involving phosphatidylinositol-3-kinase (PI3K)-protein kinase B (AKT) [45].…”