Non-coding RNAs and exercise: pathophysiological role and clinical application in the cardiovascular system

2018 ◽  
Vol 132 (9) ◽  
pp. 925-942 ◽  
Author(s):  
Clarissa P.C. Gomes ◽  
David de Gonzalo-Calvo ◽  
Rocio Toro ◽  
Tiago Fernandes ◽  
Daniel Theisen ◽  
...  

There is overwhelming evidence that regular exercise training is protective against cardiovascular disease (CVD), the main cause of death worldwide. Despite the benefits of exercise, the intricacies of their underlying molecular mechanisms remain largely unknown. Non-coding RNAs (ncRNAs) have been recognized as a major regulatory network governing gene expression in several physiological processes and appeared as pivotal modulators in a myriad of cardiovascular processes under physiological and pathological conditions. However, little is known about ncRNA expression and role in response to exercise. Revealing the molecular components and mechanisms of the link between exercise and health outcomes will catalyse discoveries of new biomarkers and therapeutic targets. Here we review the current understanding of the ncRNA role in exercise-induced adaptations focused on the cardiovascular system and address their potential role in clinical applications for CVD. Finally, considerations and perspectives for future studies will be proposed.

Author(s):  
Sabrina Carrella ◽  
Sandro Banfi ◽  
Marianthi Karali

Photoreceptors (PRs) are specialized neuroepithelial cells of the retina responsible for sensory transduction of light stimuli. In the highly structured vertebrate retina, PRs have a highly polarized modular structure to accommodate the demanding processes of phototransduction and the visual cycle. Because of their function, PRs are exposed to continuous cellular stress. PRs are therefore under pressure to maintain their function in defiance of constant environmental perturbation, besides being part of a highly sophisticated developmental process. All this translates into the need for tightly regulated and responsive molecular mechanisms that can reinforce transcriptional programs. It is commonly accepted that regulatory non-coding RNAs (ncRNAs), and in particular microRNAs (miRNAs), are not only involved but indeed central in conferring robustness and accuracy to developmental and physiological processes. Here we integrate recent findings on the role of regulatory ncRNAs (e.g., miRNAs, lncRNAs, circular RNAs, and antisense RNAs), and of their contribution to PR pathophysiology. We also outline the therapeutic implications of translational studies that harness ncRNAs to prevent PR degeneration and promote their survival and function.


2019 ◽  
Vol 14 (2) ◽  
pp. 76-83
Author(s):  
O. A. Beylerli ◽  
A. T. Beylerli ◽  
I. F. Gareev

Long non-coding RNAs (lncRNAs) are a large group of non-coding RNAs (ncRNAs) which are more than 200 nucleotides in length. LncRNAs, as regulation factors, show an important role in complex cellular processes, such as apoptosis, growth, differentiation, proliferation, etc. Recently, the results of many studies have also shown their significant role in carcinogenesis. Endogenous lncRNAs are known to be secreted by tumor cells in human biological fluids in the form of microvesicles, exosomes, or protein complexes, thereby forming circulating lncRNAs that do not degrade under the influence of RNases and are in a stable state. Compared with traditional biomarkers, as proteins circulating lncRNA have several advantages that will allow to consider circulating lncRNA as a new potential biomarker for various diseases. Aberrant expression of lncRNAs was observed in cancer patients. In this context, endogenous lncRNAs can regulate the main characteristics of cancer cells, controlling the expression of oncogenes associated with their suppressive and oncogenic functions. Consequently, circulating lncRNAs can be excellent biomarkers for cancer. Knowledge of the molecular mechanisms by which lncRNAs contribute to the development of cancer will improve our understanding of etiology, and open up horizons for the development of new biomarkers. In this paper, we will analyze current knowledge about the change in the expression profile of circulating lncRNAs in cancer, as well as methods for their detection.


2021 ◽  
Vol 14 (2) ◽  
pp. 168
Author(s):  
Marcello Francesco Lingua ◽  
Giovanna Carrà ◽  
Beatrice Maffeo ◽  
Alessandro Morotti

For many years in the field of onco-hematology much attention has been given to mutations in protein-coding genes or to genetic alterations, including large chromosomal losses or rearrangements. Despite this, biological and clinical needs in this sector remain unmet. Therefore, it is not surprising that recent studies have shifted from coded to non-coded matter. The discovery of non-coding RNAs (ncRNAs) has influenced several aspects related to the treatment of cancer. In particular, in chronic lymphocytic leukemia (CLL) the knowledge of ncRNAs and their contextualization have led to the identification of new biomarkers used to follow the course of the disease, to the anticipation of mechanisms that support resistance and relapse, and to the selection of novel targeted treatment regimens. In this review, we will summarize the main ncRNAs discovered in CLL and the molecular mechanisms by which they are affected and how they influence the development and the progression of the disease.


Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 467
Author(s):  
Iveta Bernatova ◽  
Silvia Liskova

Various studies have shown that certain flavonoids, flavonoid-containing plant extracts, and foods can improve human health. Experimental studies showed that flavonoids have the capacity to alter physiological processes as well as cellular and molecular mechanisms associated with their antioxidant properties. An important function of flavonoids was determined in the cardiovascular system, namely their capacity to lower blood pressure and to improve endothelial function. (−)-Epicatechin and taxifolin are two flavonoids with notable antihypertensive effects and multiple beneficial actions in the cardiovascular system, but they also possess antiviral effects, which may be of particular importance in the ongoing pandemic situation. Thus, this review is focused on the current knowledge of (−)-epicatechin as well as (+)-taxifolin and/or (−)-taxifolin-modified biological action and underlining molecular mechanisms determined in preclinical studies, which are relevant not only to the treatment of hypertension per se but may provide additional antiviral benefits that could be relevant to the treatment of hypertensive subjects with SARS-CoV-2 infection.


2021 ◽  
Vol 7 (4) ◽  
pp. 65
Author(s):  
Camila Caldas Martins Correia ◽  
Luis Felipe Rodrigues ◽  
Bruno Rocha de Avila Pelozin ◽  
Edilamar Menezes Oliveira ◽  
Tiago Fernandes

Despite advances in treatments and therapies, cardiovascular diseases (CVDs) remain one of the leading causes of death worldwide. The discovery that most of the human genome, although transcribed, does not encode proteins was crucial for focusing on the potential of long non-coding RNAs (lncRNAs) as essential regulators of cell function at the epigenetic, transcriptional, and post-transcriptional levels. This class of non-coding RNAs is related to the pathophysiology of the cardiovascular system. The different expression profiles of lncRNAs, in different contexts of CVDs, change a great potential in their use as a biomarker and targets of therapeutic intervention. Furthermore, regular physical exercise plays a protective role against CVDs; on the other hand, little is known about its underlying molecular mechanisms. In this review, we look at the accumulated knowledge on lncRNAs and their functions in the cardiovascular system, focusing on the cardiovascular pathology of arterial hypertension, coronary heart disease, acute myocardial infarction, and heart failure. We discuss the potential of these molecules as biomarkers for clinical use, their limitations, and how the manipulation of the expression profile of these transcripts through physical exercise can begin to be suggested as a strategy for the treatment of CVDs.


2018 ◽  
Vol 159 (47) ◽  
pp. 1962-1970 ◽  
Author(s):  
Zsolt Fejes ◽  
Bernadett Szilágyi ◽  
János Kappelmayer ◽  
Béla ifj. Nagy

Abstract: MicroRNAs (miRNA) are short, non-coding RNAs consisting of 18–25 nucleotides that regulate posttranscriptionally the gene expression involved in the regulation of physiological processes of the cells. Their key role is to modulate the translation of target mRNAs via binding to complementary sequences within the 3’ UTRs of mRNAs resulting in altered protein synthesis or even the degradation of mRNAs. miRNAs are carried not only by cells with nucleus, but also in platelets, red blood cells, and they are present in the circulation, in urine and in other body fluids as well. The fact about functional miRNAs in platelets without nucleus having a half-life of 8–12 days was questioned for a long time, thus it was also obscure whether platelets are able to produce proteins de novo when being exposed to different challenges. In the last few years, several publications have described the expression and function of certain platelet mRNAs with their regulatory miRNAs in terms of regulation of cell activation, especially in diseases in which platelet activation status is elevated, such as in type 2 diabetes mellitus or in sepsis. Apart from their pathophysiological role, miRNAs may be applied as potential new biomarkers in the investigation or differential diagnosis of these clinical conditions. This review article sought to summarize the recent findings about platelet miRNAs focusing on their altered expression in diabetes and sepsis. Orv Hetil. 2018; 159(47): 1962–1970.


2012 ◽  
Vol 367 (1595) ◽  
pp. 1469-1478 ◽  
Author(s):  
Agnieszka Bielach ◽  
Jérôme Duclercq ◽  
Peter Marhavý ◽  
Eva Benková

Phytohormones are important plant growth regulators that control many developmental processes, such as cell division, cell differentiation, organogenesis and morphogenesis. They regulate a multitude of apparently unrelated physiological processes, often with overlapping roles, and they mutually modulate their effects. These features imply important synergistic and antagonistic interactions between the various plant hormones. Auxin and cytokinin are central hormones involved in the regulation of plant growth and development, including processes determining root architecture, such as root pole establishment during early embryogenesis, root meristem maintenance and lateral root organogenesis. Thus, to control root development both pathways put special demands on the mechanisms that balance their activities and mediate their interactions. Here, we summarize recent knowledge on the role of auxin and cytokinin in the regulation of root architecture with special focus on lateral root organogenesis, discuss the latest findings on the molecular mechanisms of their interactions, and present forward genetic screen as a tool to identify novel molecular components of the auxin and cytokinin crosstalk.


2020 ◽  
Vol 66 (4) ◽  
pp. 72-84
Author(s):  
M. Khetsuriani ◽  
◽  
V. Dosenko ◽  

A large part of the human genome is transcribed into non-coding RNA. This review focuses on long noncoding RNAs (lncRNAs) involved in the regulation of gene expression. We considered information about the molecular mechanisms of of lncRNAs functioning, features of their interaction with miRNAs, mRNAs, DNA and the participation of lncRNAs in physiological and pathological processes of the cardiovascular system. In particular, the review shows the role of lncRNAs in cardiac cell differentiation, ischemic myocardial damage, cardiac hypertrophy, endothelial and smooth muscle dysfunction. Significant changes in the expression of individual lncRNAs in cardiac pathologies allow the use of these molecules for diagnostic purposes and as possible therapeutic targets.


2021 ◽  
Vol 22 (4) ◽  
pp. 2116
Author(s):  
Sonia Águila ◽  
Ascensión M. de los Reyes-García ◽  
María P. Fernández-Pérez ◽  
Laura Reguilón-Gallego ◽  
Laura Zapata-Martínez ◽  
...  

Neutrophil extracellular traps (NETs) are formed after neutrophils expelled their chromatin content in order to primarily capture and eliminate pathogens. However, given their characteristics due in part to DNA and different granular proteins, NETs may induce a procoagulant response linking inflammation and thrombosis. Unraveling NET formation molecular mechanisms as well as the intracellular elements that regulate them is relevant not only for basic knowledge but also to design diagnostic and therapeutic tools that may prevent their deleterious effects observed in several inflammatory pathologies (e.g., cardiovascular and autoimmune diseases, cancer). Among the potential elements involved in NET formation, several studies have investigated the role of microRNAs (miRNAs) as important regulators of this process. miRNAs are small non-coding RNAs that have been involved in the control of almost all physiological processes in animals and plants and that are associated with the development of several pathologies. In this review, we give an overview of the actual knowledge on NETs and their implication in pathology with a special focus in cardiovascular diseases. We also give a brief overview on miRNA biology to later focus on the different miRNAs implicated in NET formation and the perspectives opened by the presented data.


Metabolites ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 151
Author(s):  
Mehdi R. Belhaj ◽  
Nathan G. Lawler ◽  
Nolan J. Hoffman

Dynamic changes in circulating and tissue metabolites and lipids occur in response to exercise-induced cellular and whole-body energy demands to maintain metabolic homeostasis. The metabolome and lipidome in a given biological system provides a molecular snapshot of these rapid and complex metabolic perturbations. The application of metabolomics and lipidomics to map the metabolic responses to an acute bout of aerobic/endurance or resistance exercise has dramatically expanded over the past decade thanks to major analytical advancements, with most exercise-related studies to date focused on analyzing human biofluids and tissues. Experimental and analytical considerations, as well as complementary studies using animal model systems, are warranted to help overcome challenges associated with large human interindividual variability and decipher the breadth of molecular mechanisms underlying the metabolic health-promoting effects of exercise. In this review, we provide a guide for exercise researchers regarding analytical techniques and experimental workflows commonly used in metabolomics and lipidomics. Furthermore, we discuss advancements in human and mammalian exercise research utilizing metabolomic and lipidomic approaches in the last decade, as well as highlight key technical considerations and remaining knowledge gaps to continue expanding the molecular landscape of exercise biology.


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