PRMT4 overexpression aggravates cardiac remodeling following myocardial infarction by promoting cardiomyocyte apoptosis

Wang, Yilong; Ju, Chenhui; Ji, Hu; Huang, Kai; Yang, Ling

doi:10.1016/j.bbrc.2019.10.085

Cited by 20 publications

(21 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 98 , 99 Moreover, the enzyme is overexpressed in ischemic hearts and hypoxic cardiomyocytes, and it has been suggested that PRMT4 has an essential role in myocardial infarction and cardiomyocyte apoptosis. 100 Other emerging functions of PRMT4 include autophagy, metabolism, early development, pre-mRNA splicing and export, and localization to paraspeckles. 101 Also, it was recently found that in lymphomas that carry mutation in p300/CBP, PRMT4 loss or inhibition is a vulnerability.…”

Section: Resultsmentioning

confidence: 99%

Turning Nonselective Inhibitors of Type I Protein Arginine Methyltransferases into Potent and Selective Inhibitors of Protein Arginine Methyltransferase 4 through a Deconstruction–Reconstruction and Fragment-Growing Approach

et al. 2022

View full text Add to dashboard Cite

Protein arginine methyltransferases (PRMTs) are important therapeutic targets, playing a crucial role in the regulation of many cellular processes and being linked to many diseases. Yet, there is still much to be understood regarding their functions and the biological pathways in which they are involved, as well as on the structural requirements that could drive the development of selective modulators of PRMT activity. Here we report a deconstruction–reconstruction approach that, starting from a series of type I PRMT inhibitors previously identified by us, allowed for the identification of potent and selective inhibitors of PRMT4, which regardless of the low cell permeability show an evident reduction of arginine methylation levels in MCF7 cells and a marked reduction of proliferation. We also report crystal structures with various PRMTs supporting the observed specificity and selectivity.

show abstract

Section: Resultsmentioning

confidence: 99%

Turning Nonselective Inhibitors of Type I Protein Arginine Methyltransferases into Potent and Selective Inhibitors of Protein Arginine Methyltransferase 4 through a Deconstruction–Reconstruction and Fragment-Growing Approach

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Myocardial apoptosis causes ventricular remodeling, which ultimately leads to HF (26,27). Previous studies (28) have suggested that excessive production of ROS in mitochondria can cause damage to lipids and proteins of mitochondrial inner membrane, induce intimal uidity and Permeability changes, permeability transition pores (mPTP) open.…”

Section: Discussionmentioning

confidence: 99%

Tongmai Yangxin Pills Improves Cardiac Function by Enhancing the Expression of SIRT3 and PGC-1α in a Rat Model of Isoproterenol-Induced Cardiomyopathy

Zhu

Chen

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Mitochondrial biosynthesis regulated by the PGC-1α-NRF1-TFAM pathway is closely related to mitochondrial function and mitochondrial reactive oxygen generation, and is considered to be a new possible therapeutic target for the treatment of heart failure.Methods: Tongmai Yangxin Pills (TMYXP) is a Chinese patent medicine for the treatment of ischemic heart disease. It has the ability to scavenge oxygen free radicals and improve the antioxidant capacity of the heart muscle, thereby protecting cardiomyocytes, however, its mechanism is not well established. In this study, to investigate the mechanisms of TMYXP in cardiac protection, a rat model of cardiomyopathy was established by continuous isoproterenol (ISO) stimulation. Changes in the rat body weight, heart weight index (HWI), echocardiography, histological staining and biochemical indicators were examined.Results: Our results suggested that TMYXP reduced myocardial remodeling, inhibited deterioration of cardiac function, and delayed HF onset in rats with ISO-induced cardiomyopathy. Meanwhile, TMYXP markedly reduced ROS production, increased the levels of antioxidant enzymes, improved function of the mitochondrial respiratory chain, and promoted ATP production in myocardial tissues. In addition, TMYXP inhibited cytochrome C (Cyt C) release in mitochondria and caspase-3 activation in cytosol, thereby reducing the apoptosis of myocardial cells. Finally, TMYXP remarkably up-regulated the mRNA and protein expression levels of SIRT3, PGC-1α, NRF1 and TFAM in myocardial cells.Conclusions: Taken together, our results suggest that TMYXP regulates mitochondrial biosynthesis mediated enhancing the expression of SIRT3 and PGC-1α, thereby improving the cardiac function in rats with ISO-induced cardiomyopathy.

show abstract

“…Additionally, the SMC phenotype switching in atherogenic conditions can be regulated by histone arginine methylation by targeting the transcription factor ( 73 , 74 ). Protein arginine methyltransferase 4 mediates the upregulation of osteopontin through the dimethylation of R17 on histone H3, and this process promotes the recruitment of transcription factor USF1 ( 75 , 76 ). The recruitment of USF1 is suppressed by arginine demethylase JMJD6 ( 77 ).…”

Section: Histone Methylation In Cvd Progressionmentioning

confidence: 99%

Histone Methylation Related Therapeutic Challenge in Cardiovascular Diseases

Yang

Luan

Yuan

et al. 2021

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

The epidemic of cardiovascular diseases (CVDs) is predicted to spread rapidly in advanced countries accompanied by the high prevalence of risk factors. In terms of pathogenesis, the pathophysiology of CVDs is featured by multiple disorders, including vascular inflammation accompanied by simultaneously perturbed pathways, such as cell death and acute/chronic inflammatory reactions. Epigenetic alteration is involved in the regulation of genome stabilization and cellular homeostasis. The association between CVD progression and histone modifications is widely known. Among the histone modifications, histone methylation is a reversible process involved in the development and homeostasis of the cardiovascular system. Abnormal methylation can promote CVD progression. This review discusses histone methylation and the enzymes involved in the cardiovascular system and determine the effects of histone methyltransferases and demethylases on the pathogenesis of CVDs. We will further demonstrate key proteins mediated by histone methylation in blood vessels and review histone methylation-mediated cardiomyocytes and cellular functions and pathways in CVDs. Finally, we will summarize the role of inhibitors of histone methylation and demethylation in CVDs and analyze their therapeutic potential, based on previous studies.

show abstract

PRMT4 overexpression aggravates cardiac remodeling following myocardial infarction by promoting cardiomyocyte apoptosis

Cited by 20 publications

References 19 publications

Turning Nonselective Inhibitors of Type I Protein Arginine Methyltransferases into Potent and Selective Inhibitors of Protein Arginine Methyltransferase 4 through a Deconstruction–Reconstruction and Fragment-Growing Approach

Turning Nonselective Inhibitors of Type I Protein Arginine Methyltransferases into Potent and Selective Inhibitors of Protein Arginine Methyltransferase 4 through a Deconstruction–Reconstruction and Fragment-Growing Approach

Tongmai Yangxin Pills Improves Cardiac Function by Enhancing the Expression of SIRT3 and PGC-1α in a Rat Model of Isoproterenol-Induced Cardiomyopathy

Histone Methylation Related Therapeutic Challenge in Cardiovascular Diseases

Contact Info

Product

Resources

About