miR-30a downregulation aggravates pressure overload-induced cardiomyocyte hypertrophy

Yin, Xue-Song; Peng, Chenghai; Ning, Wenhu; Li, Chunyan; Ren, Zhongqiao; Zhang, Jihong; Gao, Han; Kan, Zhao

doi:10.1007/s11010-012-1552-z

Cited by 50 publications

(34 citation statements)

References 23 publications

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“…Reduced abundance of the autophagy repressing microRNA-30a accelerates progression of cardiac hypertrophy after TAC [50], and pharmacological inhibition of autophagy by 3-methyladenine (3-MA) reduces fibrosis in the same model [51]. Genetic models in which autophagic flux is increased in cardiomyocytes by over-expression of Beclin 1 or reduced by haploinsufficiency of the gene coding for this protein, result in amplified or attenuated pressure overload-induced HF, respectively.…”

Section: Autophagy In Cardiac Hypertrophy and Failurementioning

confidence: 99%

Therapeutic targeting of autophagy in cardiovascular disease

Schiattarella

Hill²

2016

Journal of Molecular and Cellular Cardiology

151

122

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Autophagy is an evolutionarily ancient process of intracellular catabolism necessary to preserve cellular homeostasis in response to a wide variety of stresses. In the case of post-mitotic cells, where cell replacement is not an option, finely tuned quality control of cytoplasmic constituents and organelles is especially critical. And due to the ubiquitous and critical role of autophagic flux in the maintenance of cell health, it comes as little surprise that perturbation of the autophagic process is observed in multiple disease processes. A large body of preclinical evidence suggests that autophagy is a double-edged sword in cardiovascular disease, acting in either beneficial or maladaptive ways, depending on the context. In light of this, the autophagic machinery in cardiomyocytes and other cardiovascular cell types has been proposed as a potential therapeutic target. Here, we summarize current knowledge regarding the dual functions of autophagy in cardiovascular disease. We go on to analyze recent evidence suggesting that titration of autophagic flux holds potential as a novel treatment strategy.

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Section: Autophagy In Cardiac Hypertrophy and Failurementioning

confidence: 99%

Therapeutic targeting of autophagy in cardiovascular disease

Schiattarella

Hill²

2016

Journal of Molecular and Cellular Cardiology

151

122

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“…aggravate pressure overload-induced cardiomyocyte hypertrophy via activating autophagy signaling (Yin et al, 2013). Whether Beclin-1 can be repressed by microRNA-30a in the heart to attenuate pressure overload-induced cardiac hypertrophy requires further investigation.…”

Section: Atf3 Regulates Cardiac Hypertrophymentioning

confidence: 99%

Activating Transcription Factor 3 Protects against Pressure-Overload Heart Failure via the Autophagy Molecule Beclin-1 Pathway

Lin

Chen

et al. 2014

Mol Pharmacol

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Activating transcription factor 3 (ATF3), a cAMP response element-binding protein/ATF family transcription factors member, has been implicated in the cardiovascular and inflammatory system and is rapidly induced by ischemic-reperfusion injuries. We performed transverse aortic banding (TAB) experiments using ATF3 gene-deleted mice (ATF3 2/2 ) and wild-type (WT) mice to determine what effect it might have on heart failure induced by pressure overloading. Compared with the WT mice, ATF3 2/2 mice were found by echocardiography to have decreased left ventricular contractility with loss of normal cardiac hypertrophic remodeling. The ATF3 2/2 mice had greater numbers of terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine nick-end labeling-positive cells and higher levels of activated caspase-3, as well as more apoptosis. Restoration of ATF3 expression in the heart of ATF3 2/2 mice by adenovirus-induced ATF3 treatment significantly improved cardiac contractility after TAB. The results from molecular and biochemical analyses, including chromatin immune-precipitation and in vitro /in vivo promoter assays, showed that ATF3 bound to the ATF/cAMP response element of the Beclin-1 promoter and that ATF3 reduced autophagy via suppression of the Beclin-1-dependent pathway. Furthermore, infusion of tert-butylhydroquinone (tBHQ), a selective ATF3 inducer, increased the expression of ATF3 via the nuclear factor erythroid 2-related transcriptional factor, inhibited TABinduced cardiac dilatation, and increased left ventricular contractility, thereby rescuing heart failure. Our study identified a new epigenetic regulation mediated by the stress-inducible gene ATF3 on TAB-induced cardiac dysfunction. These findings suggest that the ATF3 activator tBHQ may have therapeutic potential for the treatment of pressure-overload heart failure induced by chronic hypertension or other pressure overload mechanisms.

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“…15 Recent studies have highlighted the role of LC3B in monitoring autophagic activity in myocardial hypertrophy. [16][17][18] However, it remains to be determined whether LC3B impacts autophagic activity during cardiomyocyte hypertrophy and whether LC3B modulates cardiomyocyte hypertrophy. In this study, we investigated the well-established in vitro angiotensin II (Ang II)-stimulated cardiomyocyte hypertrophy model.…”

Section: Introductionmentioning

confidence: 99%

LC3B, a Protein That Serves as an Autophagic Marker, Modulates Angiotensin II-induced Myocardial Hypertrophy

Huang¹,

Pan

et al. 2015

Journal of Cardiovascular Pharmacology

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LC3B is a marker of autophagic activity, and growing evidence supports its importance in myocardial hypertrophy. Thus, regulating LC3B expression may provide an important avenue to inhibit autophagy and protect against or inhibit pathological myocardial hypertrophy. To address this question, we investigated the effects of altering LC3B mRNA expression and autophagic activity in the setting of cardiomyocyte hypertrophy. In an in vitro angiotensin II (Ang II)-induced cardiomyocyte hypertrophy model, LC3B mRNA and protein expression was increased and there was activation of cardiomyocyte autophagy, which was assessed by transmission electron microscopy and flow cytometry. LC3B cDNA transfection also resulted in an upregulation of autophagic activity, whereas downregulation of autophagic activity was observed with knockdown of LC3B expression. Induction of LC3B expression was shown to further exacerbate Ang II-stimulated cardiomyocyte hypertrophy, whereas inhibition of LC3B expression inhibited the Ang II-stimulated cardiomyocyte hypertrophy (as assessed through cardiomyocyte morphology and expression of ANP and β-MHC). This study demonstrated that LC3B modulates the Ang II-induced cardiomyocyte hypertrophy in cultured neonatal rat ventricular cardiomyocytes.

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miR-30a downregulation aggravates pressure overload-induced cardiomyocyte hypertrophy

Cited by 50 publications

References 23 publications

Therapeutic targeting of autophagy in cardiovascular disease

Therapeutic targeting of autophagy in cardiovascular disease

Activating Transcription Factor 3 Protects against Pressure-Overload Heart Failure via the Autophagy Molecule Beclin-1 Pathway

LC3B, a Protein That Serves as an Autophagic Marker, Modulates Angiotensin II-induced Myocardial Hypertrophy

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