Potential epigenetic therapeutics for atherosclerosis treatment

Nicorescu, Ioana; Dallinga, Geesje M.; Winther, Menno P.J. de; Stroes, Erik S.G.; Bahjat, Mahnoush

doi:10.1016/j.atherosclerosis.2018.10.006

Cited by 37 publications

(29 citation statements)

References 102 publications

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“…Histone acetylation, characterized by the addition of positively charged acetyl groups to amino acid residues at the level of histone tails, reduces the affinity of histones for DNA thus increasing chromatin accessibility (76). Acetylation occurs mainly on lysine residues on histones H3 and H4; this mark mainly associates with activation of transcription by enhancing chromatin accessibility (77).…”

Section: Histone Modificationsmentioning

confidence: 99%

Epigenetic Control of Mitochondrial Function in the Vasculature

Mohammed

Ambrosini

Lüscher

et al. 2020

Front. Cardiovasc. Med.

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The molecular signatures of epigenetic regulation and chromatin architecture are emerging as pivotal regulators of mitochondrial function. Recent studies unveiled a complex intersection among environmental factors, epigenetic signals, and mitochondrial metabolism, ultimately leading to alterations of vascular phenotype and increased cardiovascular risk. Changing environmental conditions over the lifetime induce covalent and post-translational chemical modification of the chromatin template which sensitize the genome to establish new transcriptional programs and, hence, diverse functional states. On the other hand, metabolic alterations occurring in mitochondria affect the availability of substrates for chromatin-modifying enzymes, thus leading to maladaptive epigenetic signatures altering chromatin accessibility and gene transcription. Indeed, several components of the epigenetic machinery require intermediates of cellular metabolism (ATP, AcCoA, NADH, α-ketoglutarate) for enzymatic function. In the present review, we describe the emerging role of epigenetic modifications as fine tuners of gene transcription in mitochondrial dysfunction and vascular disease. Specifically, the following aspects are described in detail: (i) mitochondria and vascular function, (ii) mitochondrial ROS, (iii) epigenetic regulation of mitochondrial function; (iv) the role of mitochondrial metabolites as key effectors for chromatin-modifying enzymes; (v) epigenetic therapies. Understanding epigenetic routes may pave the way for new approaches to develop personalized therapies to prevent mitochondrial insufficiency and its complications.

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Section: Histone Modificationsmentioning

confidence: 99%

Epigenetic Control of Mitochondrial Function in the Vasculature

Mohammed

Ambrosini

Lüscher

et al. 2020

Front. Cardiovasc. Med.

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“…A better understanding of the epigenetic background of the mechanisms underlying some pathological processes could potentially turn into novel therapeutic strategies, including the treatment of atherosclerosis [14]. In that context, the histone-modifying enzymes seem to be an attractive new target.…”

Section: Atherosclerosismentioning

confidence: 99%

“…In that context, the histone-modifying enzymes seem to be an attractive new target. A few groups of enzymes are the subject of particular interest: histone methyltransferases (HMT) responsible for both lysine and arginine residues methylation, histone demethylases (HDMs) exhibiting opposite activity, and histone deacetylases (HDAC), which counteract acetyltransferases (HAT) activity by removing acetyl-groups from histones [14,15]. It has been demonstrated that through the use of pharmacological inhibitors H3K27me3 demethylases Jmjd3 and Utx, the suppression of LPS-induced production of TNF-α in human monocytes/macrophages is possible.…”

Section: Atherosclerosismentioning

confidence: 99%

Trained Innate Immunity Not Always Amicable

Włodarczyk

Druszczyńska

Fol

2019

IJMS

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The concept of “trained innate immunity” is understood as the ability of innate immune cells to remember invading agents and to respond nonspecifically to reinfection with increased strength. Trained immunity is orchestrated by epigenetic modifications leading to changes in gene expression and cell physiology. Although this phenomenon was originally seen mainly as a beneficial effect, since it confers broad immunological protection, enhanced immune response of reprogrammed innate immune cells might result in the development or persistence of chronic metabolic, autoimmune or neuroinfalmmatory disorders. This paper overviews several examples where the induction of trained immunity may be essential in the development of diseases characterized by flawed innate immune response.

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“…In the last decade, increasing evidence has helped to characterize the role of abnormal epigenetic modulation in the development of cardiovascular diseases. Differential DNA methylation profiles are observed in patients with cardiovascular diseases in tissues and cells (including aortic lesions, vascular endothelium, and monocytes) [59], histone methylation and acetylation, which indicates the therapeutic potential for the regulation of epigenetic processes (Figure 2).…”

Section: Epigenetic Regulation In the Treatment Of Atherosclerosismentioning

confidence: 99%

“…Histone acetyltransferase (HAT) and histone deacetylase (HDAC) are the main enzymes that play an important role in determining the state of histone acetylation [80]. Post-translational histone methyltransferases (HMTs), histone demethylases (HDM), histone deacetylases (HDACs) and histone acetyltransferases (HATs) can also affect gene expression, depending on the site and number of modifications (Figure 2) [59].…”

Section: Epigenetic Regulation In the Treatment Of Atherosclerosismentioning

confidence: 99%

Promising Directions in Atherosclerosis Treatment Based on Epigenetic Regulation Using MicroRNAs and Long Noncoding RNAs

et al. 2019

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Atherosclerosis is one of the leading causes of mortality from cardiovascular disease (CVD) and is a chronic inflammatory disease of the middle and large arteries caused by a disruption of lipid metabolism. Noncoding RNA (ncRNA), including microRNA (miRNA), small interfering RNA (siRNA) and long noncoding RNA (lncRNA), was investigated for the treatment of atherosclerosis. Regulation of the expression of noncoding RNA targets the constituent element of the pathogenesis of atherosclerosis. Currently, miRNA therapy commonly employs miRNA antagonists and mimic compounds. In this review, attention is focused on approaches to correcting molecular disorders based on the genetic regulation of the transcription of key genes responsible for the development of atherosclerosis. Promising technologies were considered for the treatment of atherosclerosis, and examples are given for technologies that have been shown to be effective in clinical trials.

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Potential epigenetic therapeutics for atherosclerosis treatment

Cited by 37 publications

References 102 publications

Epigenetic Control of Mitochondrial Function in the Vasculature

Epigenetic Control of Mitochondrial Function in the Vasculature

Trained Innate Immunity Not Always Amicable

Promising Directions in Atherosclerosis Treatment Based on Epigenetic Regulation Using MicroRNAs and Long Noncoding RNAs

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