MicroRNA-214 contributes to Ang II-induced cardiac hypertrophy by targeting SIRT3 to provoke mitochondrial malfunction

Ding, Yanqing; Zhang, Yuhong; Lu, Jing; Li, Bai; Yu, Wei; Yue, Zhongbao; Hu, Yuehuai; Wang, Panxia; Li, Jingyan; Cai, Sidong; Ye, Jiantao

doi:10.1038/s41401-020-00563-7

Cited by 24 publications

(11 citation statements)

References 57 publications

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“… 503 SIRT3 has a protective role in cardiac hypertrophy. 504 Its expression was reduced in the hearts of Ang II-induced cardiac hypertrophic mice and in Ang II-treated cardiomyocytes. 505 In addition, SIRT3 overexpression protects myocytes from hypertrophy, whereas SIRT3 silencing exacerbates Ang II-induced cardiomyocyte hypertrophy.…”

Section: Introductionmentioning

confidence: 97%

The sirtuin family in health and disease

Zhang

Chen

et al. 2022

Sig Transduct Target Ther

223

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Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, and are involved in numerous biological processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles of seven members of the SIRT family in health and disease conditions. Notably, this protein family plays a variety of important roles in cellular biology such as inflammation, metabolism, oxidative stress, and apoptosis, etc., thus, it is considered a potential therapeutic target for different kinds of pathologies including cancer, cardiovascular disease, respiratory disease, and other conditions. Moreover, identification of SIRT modulators and exploring the functions of these different modulators have prompted increased efforts to discover new small molecules, which can modify SIRT activity. Furthermore, several randomized controlled trials have indicated that different interventions might affect the expression of SIRT protein in human samples, and supplementation of SIRT modulators might have diverse impact on physiological function in different participants. In this review, we introduce the history and structure of the SIRT protein family, discuss the molecular mechanisms and biological functions of seven members of the SIRT protein family, elaborate on the regulatory roles of SIRTs in human disease, summarize SIRT inhibitors and activators, and review related clinical studies.

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Section: Introductionmentioning

confidence: 97%

The sirtuin family in health and disease

Zhang

Chen

et al. 2022

Sig Transduct Target Ther

223

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“…OCR measurement was performed using an XF96 Extracellular Flux Analyzer (Seahorse Bioscience, North Billerica, MA, United States) with Seahorse XFp Cell Mito Stress Test Kit (Seahorse Bioscience) as described previously ( Ding et al, 2021 ). Briefly, H9c2 cells were seeded into Seahorse XF96 microplates in a density of 2×10 4 cells/well.…”

Section: Methodsmentioning

confidence: 99%

Epigenetic Reader Bromodomain Containing Protein 2 Facilitates Pathological Cardiac Hypertrophy via Regulating the Expression of Citrate Cycle Genes

Zhong

Guo

et al. 2022

Front. Pharmacol.

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The bromodomain and extra-terminal domain proteins (BETs) family serve as epigenetic “readers”, which recognize the acetylated histones and recruit transcriptional regulator complexes to chromatin, eventually regulating gene transcription. Accumulating evidences demonstrate that pan BET inhibitors (BETi) confer protection against pathological cardiac hypertrophy, a precursor progress for developing heart failure. However, the roles of BET family members, except BRD4, remain unknown in pathological cardiac hypertrophy. The present study identified BRD2 as a novel regulator in cardiac hypertrophy, with a distinct mechanism from BRD4. BRD2 expression was elevated in cardiac hypertrophy induced by β-adrenergic agonist isoprenaline (ISO) in vivo and in vitro. Overexpression of BRD2 upregulated the expression of hypertrophic biomarkers and increased cell surface area, whereas BRD2 knockdown restrained ISO-induced cardiomyocyte hypertrophy. In vivo, rats received intramyocardial injection of adeno-associated virus (AAV) encoding siBRD2 significantly reversed ISO-induced pathological cardiac hypertrophy, cardiac fibrosis, and cardiac function dysregulation. The bioinformatic analysis of whole-genome sequence data demonstrated that a majority of metabolic genes, in particular those involved in TCA cycle, were under regulation by BRD2. Real-time PCR results confirmed that the expressions of TCA cycle genes were upregulated by BRD2, but were downregulated by BRD2 silencing in ISO-treated cardiomyocytes. Results of mitochondrial oxygen consumption rate (OCR) and ATP production measurement demonstrated that BRD2 augmented cardiac metabolism during cardiac hypertrophy. In conclusion, the present study revealed that BRD2 could facilitate cardiac hypertrophy through upregulating TCA cycle genes. Strategies targeting inhibition of BRD2 might suggest therapeutic potential for pathological cardiac hypertrophy and heart failure.

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“…On the other hand, miR-214 aggravates cardiac hypertrophy by targeting and inhibiting sirtuin 3 (SIRT3), impairing mitochondrial function and perturbing energy metabolism. While overexpression of miR-214 leads to mitochondrial damage and cardiac hypertrophy in mice, its silencing attenuates mitochondrial injury and decreases the hypertrophic response [ 97 ].…”

Section: Ncrnas In Pressure-overload-induced Cardiac Hypertrophymentioning

confidence: 99%

Non-Coding RNAs in the Therapeutic Landscape of Pathological Cardiac Hypertrophy

Silva

Martins

2022

Cells

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Cardiovascular diseases are a major health problem, and long-term survival for people diagnosed with heart failure is, still, unrealistic. Pathological cardiac hypertrophy largely contributes to morbidity and mortality, as effective therapeutic approaches are lacking. Non-coding RNAs (ncRNAs) arise as active regulators of the signaling pathways and mechanisms that govern this pathology, and their therapeutic potential has received great attention in the last decades. Preclinical studies in large animal models have been successful in ameliorating cardiac hypertrophy, and an antisense drug for the treatment of heart failure has, already, entered clinical trials. In this review, we provide an overview of the molecular mechanisms underlying cardiac hypertrophy, the involvement of ncRNAs, and the current therapeutic landscape of oligonucleotides targeting these regulators. Strategies to improve the delivery of such therapeutics and overcome the actual challenges are, also, defined and discussed. With the fast advance in the improvement of oligonucleotide drug delivery, the inclusion of ncRNAs-targeting therapies for cardiac hypertrophy seems, increasingly, a closer reality.

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MicroRNA-214 contributes to Ang II-induced cardiac hypertrophy by targeting SIRT3 to provoke mitochondrial malfunction

Cited by 24 publications

References 57 publications

The sirtuin family in health and disease

The sirtuin family in health and disease

Epigenetic Reader Bromodomain Containing Protein 2 Facilitates Pathological Cardiac Hypertrophy via Regulating the Expression of Citrate Cycle Genes

Non-Coding RNAs in the Therapeutic Landscape of Pathological Cardiac Hypertrophy

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