• Home
  • Search Results
  • HDACs Regulate miR-133a Expression in Pressure Overload-Induced Cardiac Fibrosis.

HDACs Regulate miR-133a Expression in Pressure Overload-Induced Cardiac Fibrosis.

Circulation. Heart failure (2015-09-16)
Ludivine Renaud, Lillianne G Harris, Santhosh K Mani, Harinath Kasiganesan, James C Chou, Catalin F Baicu, An Van Laer, Adam W Akerman, Robert E Stroud, Jeffrey A Jones, Michael R Zile, Donald R Menick
ABSTRACT

MicroRNAs (miRNAs) and histone deacetylases (HDACs) serve a significant role in the pathogenesis of a variety of cardiovascular diseases. The transcriptional regulation of miRNAs is poorly understood in cardiac hypertrophy. We investigated whether the expression of miR-133a is epigenetically regulated by class I and IIb HDACs during hypertrophic remodeling. Transverse aortic constriction (TAC) was performed in CD1 mice to induce pressure overload hypertrophy. Mice were treated with class I and IIb HDAC inhibitor (HDACi) via drinking water for 2 and 4 weeks post TAC. miRNA expression was determined by real-time polymerase chain reaction. Echocardiography was performed at baseline and post TAC end points for structural and functional assessment. Chromatin immunoprecipitation was used to identify HDACs and transcription factors associated with miR-133a promoter. miR-133a expression was downregulated by 0.7- and 0.5-fold at 2 and 4 weeks post TAC, respectively, when compared with vehicle control (P<0.05). HDAC inhibition prevented this significant decrease 2 weeks post TAC and maintained miR-133a expression near vehicle control levels, which coincided with (1) a decrease in connective tissue growth factor expression, (2) a reduction in cardiac fibrosis and left atrium diameter (marker of end-diastolic pressure), suggesting an improvement in diastolic function. Chromatin immunoprecipitation analysis revealed that HDAC1 and HDAC2 are present on the miR-133a enhancer regions. The results reveal that HDACs play a role in the regulation of pressure overload-induced miR-133a downregulation. This work is the first to provide insight into an epigenetic-miRNA regulatory pathway in pressure overload-induced cardiac fibrosis.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Dichloromethane, anhydrous, ≥99.8%, contains 40-150 ppm amylene as stabilizer
Sigma-Aldrich
Dichloromethane, puriss. p.a., ACS reagent, reag. ISO, ≥99.9% (GC)
Sigma-Aldrich
Dichloromethane, contains 40-150 ppm amylene as stabilizer, ACS reagent, ≥99.5%
Sigma-Aldrich
BIS-TRIS, ≥98.0% (titration)
Sigma-Aldrich
Monoclonal Anti-α-Tubulin antibody produced in mouse, clone DM1A, ascites fluid
Sigma-Aldrich
Dichloromethane, puriss., meets analytical specification of Ph. Eur., NF, ≥99% (GC)
Sigma-Aldrich
Dichloromethane, ACS reagent, ≥99.5%, contains 40-150 ppm amylene as stabilizer
SAFC
BIS-TRIS
Sigma-Aldrich
Dichloromethane, suitable for HPLC, ≥99.9%, contains 40-150 ppm amylene as stabilizer
Sigma-Aldrich
7-Amino-4-methylcoumarin, 99%
Sigma-Aldrich
7-Amino-4-methylcoumarin, Chromophore for substrates
Sigma-Aldrich
BIS-TRIS, BioXtra, ≥98.0% (titration)
Sigma-Aldrich
BIS-TRIS, BioUltra, ≥99.0% (NT)
Sigma-Aldrich
BIS-TRIS, BioPerformance Certified, suitable for cell culture, suitable for insect cell culture, ≥98.0%
Sigma-Aldrich
Dichloromethane, ACS reagent, ≥99.5%, contains 40-150 ppm amylene as stabilizer
Sigma-Aldrich
Anti-Histone H3 Antibody, 0.5 mg/mL, Upstate®
Supelco
Dichloromethane, analytical standard, stabilized
Sigma-Aldrich
Dichloromethane, biotech. grade, 99.9%, contains 40-150 ppm amylene as stabilizer
Supelco
Dichloromethane solution, certified reference material, 200 μg/mL in methanol
Supelco
Dichloromethane solution, certified reference material, 5000 μg/mL in methanol
SAFC
BIS-TRIS
Supelco
Dichloromethane solution, contains 10 % (v/v) methanol
Supelco
Dichloromethane, ≥99.9%

Social Media

LinkedIn icon
Twitter icon
Facebook Icon
Instagram Icon

MilliporeSigma

Research. Development. Production.

We are a leading supplier to the global Life Science industry with solutions and services for research, biotechnology development and production, and pharmaceutical drug therapy development and production.

© 2021 Merck KGaA, Darmstadt, Germany and/or its affiliates. All Rights Reserved.

Reproduction of any materials from the site is strictly forbidden without permission.