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Published on: June 3, 2018
Targeting miR-30d reverses pathological cardiac hypertrophy.
Jin Li1, Zhao Sha1, Xiaolan Zhu1
1Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong 226011, China; Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, Shanghai Engineering Research Center of Organ Repair, School of Life Science, Shanghai University, Shanghai 200444, China.
MicroRNA-30d (miR-30d) levels decrease in pathological cardiac hypertrophy. Restoring miR-30d ameliorates cardiac hypertrophy by targeting key genes and pathways, offering a potential therapeutic strategy for heart failure.
Area of Science:
- Molecular Biology
- Cardiovascular Research
- Biochemistry
Background:
- Pathological cardiac hypertrophy is a precursor to heart failure (HF).
- Effective therapies for pathological cardiac hypertrophy are urgently needed.
- MicroRNAs play crucial roles in regulating cardiac function and disease.
Purpose of the Study:
- To investigate the role of miR-30d in pathological cardiac hypertrophy.
- To elucidate the molecular mechanisms underlying miR-30d's function in cardiac hypertrophy.
- To evaluate the therapeutic potential of miR-30d in treating cardiac hypertrophy and HF.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to measure miR-30d expression in hypertrophy models and patient serum.
- In vitro and in vivo gain- and loss-of-function experiments for miR-30d.
- Bioinformatics, western blot, luciferase assays, and immunofluorescence to determine molecular mechanisms.
Main Results:
- miR-30d expression was significantly decreased in cardiac hypertrophy models and chronic heart failure patients.
- Overexpression of miR-30d attenuated hypertrophy induced by phenylephrine (PE) and angiotensin II (Ang II) in cardiomyocytes.
- miR-30d protected against isoproterenol (ISO)-induced cardiac hypertrophy in transgenic rats and ameliorated hypertrophy in human cells.
Conclusions:
- miR-30d acts as a protective microRNA against pathological cardiac hypertrophy.
- miR-30d functions by inhibiting pro-hypertrophic pathways, including NFAT signaling, via targeting MAP4K4 and GRP78.
- Restoring miR-30d levels, potentially via adeno-associated virus (AAV) vectors, represents a promising therapeutic strategy for cardiac hypertrophy and heart failure.
