Epigenetic Signaling and RNA Regulation in Cardiovascular Diseases

Mongelli, Alessia; Atlante, Sandra; Bachetti, Tiziana; Martelli, Fabio; Farsetti, Antonella; Gaetano, Carlo

doi:10.3390/ijms21020509

Cited by 22 publications

(26 citation statements)

References 87 publications

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“…Dunn et al demonstrated that disturbed blood flow stimulates DNA methyltransferase-1 (DNMT-1) expression in endothelial cells with aberrant DNA methylation at the promoter of flow-inducible genes, contributing to atherosclerosis [ 28 ]. Finally, recent data showed the role of non-coding RNA in regulating the expression of endothelial adhesion molecule [ 29 ].…”

Section: Endothelial Dysfunctionmentioning

confidence: 99%

Endothelium as a Source and Target of H2S to Improve Its Trophism and Function

2021

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The vascular endothelium consists of a single layer of squamous endothelial cells (ECs) lining the inner surface of blood vessels. Nowadays, it is no longer considered as a simple barrier between the blood and vessel wall, but a central hub to control blood flow homeostasis and fulfill tissue metabolic demands by furnishing oxygen and nutrients. The endothelium regulates the proper functioning of vessels and microcirculation, in terms of tone control, blood fluidity, and fine tuning of inflammatory and redox reactions within the vessel wall and in surrounding tissues. This multiplicity of effects is due to the ability of ECs to produce, process, and release key modulators. Among these, gasotransmitters such as nitric oxide (NO) and hydrogen sulfide (H2S) are very active molecules constitutively produced by endotheliocytes for the maintenance and control of vascular physiological functions, while their impairment is responsible for endothelial dysfunction and cardiovascular disorders such as hypertension, atherosclerosis, and impaired wound healing and vascularization due to diabetes, infections, and ischemia. Upregulation of H2S producing enzymes and administration of H2S donors can be considered as innovative therapeutic approaches to improve EC biology and function, to revert endothelial dysfunction or to prevent cardiovascular disease progression. This review will focus on the beneficial autocrine/paracrine properties of H2S on ECs and the state of the art on H2S potentiating drugs and tools.

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Section: Endothelial Dysfunctionmentioning

confidence: 99%

Endothelium as a Source and Target of H2S to Improve Its Trophism and Function

2021

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“…Of note, depending on the subcellular localization, lncRNAs can mimic transcription factor binding sites, acting as a decoy, or can bind to exon/intron junctions of pre-mRNA and influence the splicing process [43]. Recently, researchers provide evidence about modifications in RNA molecules such as the methylation of adenine in position 1 (N1-methyladenosine, m1A) and 6 (N6-methyladenosine, m6A) performed by the N6-adenosine methyltransferase-like 3 (METTL3) [44][45][46]. In particular, mRNAs stability is altered when m6A occurs at their 5′-AGG (m6) AC-3′ consensus sequence, affecting their translation efficiency.…”

Section: Epigeneticsmentioning

confidence: 99%

The epigenetic implication in coronavirus infection and therapy

et al. 2020

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Epigenetics is a relatively new field of science that studies the genetic and non-genetic aspects related to heritable phenotypic changes, frequently caused by environmental and metabolic factors. In the host, the epigenetic machinery can regulate gene expression through a series of reversible epigenetic modifications, such as histone methylation and acetylation, DNA/RNA methylation, chromatin remodeling, and non-coding RNAs. The coronavirus disease 19 (COVID-19) is a highly transmittable and pathogenic viral infection. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which emerged in Wuhan, China, and spread worldwide, causes it. COVID-19 severity and consequences largely depend on patient age and health status. In this review, we will summarize and comparatively analyze how viruses regulate the host epigenome. Mainly, we will be focusing on highly pathogenic respiratory RNA virus infections such as coronaviruses. In this context, epigenetic alterations might play an essential role in the onset of coronavirus disease complications. Although many therapeutic approaches are under study, more research is urgently needed to identify effective vaccine or safer chemotherapeutic drugs, including epigenetic drugs, to cope with this viral outbreak and to develop pre- and post-exposure prophylaxis against COVID-19.

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“…These different modifications are classified into groups based on their different characteristics. These groups include classification into reversible and non-reversible (where erasers are lacking), substitutional and non-substitutional ( 32 ), cap (where the modifications happen to the 5′-end of the RNAs) or internal modifications [where the modifications occur within the 5′- or 3′-untranslated regions (UTRs) or within transcript introns] ( 33 ), and finally, modifications on coding or ncRNAs ( 34 ). NcRNAs have now been studied extensively and have been proven to have important regulatory effects in both physiological and pathological conditions.…”

Section: Prevalence Of Epitranscriptomics In Cvd and Their Ac-tivitymentioning

confidence: 99%

Epitranscriptomics of cardiovascular diseases (Review)

et al. 2021

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RNA modifications have recently become the focus of attention due to their extensive regulatory effects in a vast array of cellular networks and signaling pathways. Just as epigenetics is responsible for the imprinting of environmental conditions on a genetic level, epitranscriptomics follows the same principle at the RNA level, but in a more dynamic and sensitive manner. Nevertheless, its impact in the field of cardiovascular disease (CVD) remains largely unexplored. CVD and its associated pathologies remain the leading cause of death in Western populations due to the limited regenerative capacity of the heart. As such, maintenance of cardiac homeostasis is paramount for its physiological function and its capacity to respond to environmental stimuli. In this context, epitranscriptomic modifications offer a novel and promising therapeutic avenue, based on the fine-tuning of regulatory cascades, necessary for cardiac function. This review aimed to provide an overview of the most recent findings of key epitranscriptomic modifications in both coding and non-coding RNAs. Additionally, the methods used for their detection and important associations with genetic variations in the context of CVD were summarized. Current knowledge on cardiac epitranscriptomics, albeit limited still, indicates that the impact of epitranscriptomic editing in the heart, in both physiological and pathological conditions, holds untapped potential for the development of novel targeted therapeutic approaches in a dynamic manner.

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Epigenetic Signaling and RNA Regulation in Cardiovascular Diseases

Cited by 22 publications

References 87 publications

Endothelium as a Source and Target of H2S to Improve Its Trophism and Function

Endothelium as a Source and Target of H2S to Improve Its Trophism and Function

The epigenetic implication in coronavirus infection and therapy

Epitranscriptomics of cardiovascular diseases (Review)

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