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MicroRNAs in cardiovascular disease: an introduction for clinicians.

ABSTRACT: MicroRNAs (miRNAs) are small, non-coding, RNA molecules approximately 22 nucleotides in length which act as post-transcriptional regulators of gene expression. Individual miRNAs have been shown to regulate the expression of multiple genes. Conversely, the expression of individual genes can be regulated by multiple miRNAs. Consequently, since their discovery just over 20 years ago, miRNAs have been identified as key regulators of complex biological processes linked to multiple cardiovascular pathologies, including left ventricular hypertrophy, ischaemic heart disease, heart failure, hypertension and arrhythmias. Furthermore, since the finding that miRNAs are present in the circulation, they have been investigated as novel biomarkers, especially in the context of acute myocardial infarction (AMI) and heart failure. While there is little convincing evidence that miRNAs can outperform traditional biomarkers, such as cardiac troponins, in the diagnosis of AMI, there is potential for miRNAs to complement existing risk prediction models and act as valuable markers of post-AMI prognosis. Encouragingly, the concept of miRNA-based therapeutics is developing, with synthetic antagonists of miRNAs (antagomiRs) currently in phase II trials for the treatment of chronic hepatitis C virus infection. In the cardiovascular field, promising preclinical studies suggest that they could be useful in treating disorders ranging from heart failure to dyslipidaemia, although several challenges related to specificity and targeted delivery remain to be overcome. Through this review, we provide clinicians with a brief overview of the ever-expanding world of miRNAs.

SUBMITTER: Romaine SP

PROVIDER: S-EPMC4484262 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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MicroRNAs in cardiovascular disease: an introduction for clinicians.

Romaine Simon P R SP Tomaszewski Maciej M Condorelli Gianluigi G Samani Nilesh J NJ

Heart (British Cardiac Society) 20150326 12

MicroRNAs (miRNAs) are small, non-coding, RNA molecules approximately 22 nucleotides in length which act as post-transcriptional regulators of gene expression. Individual miRNAs have been shown to regulate the expression of multiple genes. Conversely, the expression of individual genes can be regulated by multiple miRNAs. Consequently, since their discovery just over 20 years ago, miRNAs have been identified as key regulators of complex biological processes linked to multiple cardiovascular path ...[more]

PMID: 25814653

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Project description:There are many excellent specialised texts and articles that describe the physical principles of cardiovascular magnetic resonance (CMR) techniques. There are also many texts written with the clinician in mind that provide an understandable, more general introduction to the basic physical principles of magnetic resonance (MR) techniques and applications. There are however very few texts or articles that attempt to provide a basic MR physics introduction that is tailored for clinicians using CMR in their daily practice. This is the first of two reviews that are intended to cover the essential aspects of CMR physics in a way that is understandable and relevant to this group. It begins by explaining the basic physical principles of MR, including a description of the main components of an MR imaging system and the three types of magnetic field that they generate. The origin and method of production of the MR signal in biological systems are explained, focusing in particular on the two tissue magnetisation relaxation properties (T1 and T2) that give rise to signal differences from tissues, showing how they can be exploited to generate image contrast for tissue characterisation. The method most commonly used to localise and encode MR signal echoes to form a cross sectional image is described, introducing the concept of k-space and showing how the MR signal data stored within it relates to properties within the reconstructed image. Before describing the CMR acquisition methods in detail, the basic spin echo and gradient pulse sequences are introduced, identifying the key parameters that influence image contrast, including appearances in the presence of flowing blood, resolution and image acquisition time. The main derivatives of these two pulse sequences used for cardiac imaging are then described in more detail. Two of the key requirements for CMR are the need for data acquisition first to be to be synchronised with the subject's ECG and to be fast enough for the subject to be able to hold their breath. Methods of ECG synchronisation using both triggering and retrospective gating approaches, and accelerated data acquisition using turbo or fast spin echo and gradient echo pulse sequences are therefore outlined in some detail. It is shown how double inversion black blood preparation combined with turbo or fast spin echo pulse sequences acquisition is used to achieve high quality anatomical imaging. For functional cardiac imaging using cine gradient echo pulse sequences two derivatives of the gradient echo pulse sequence; spoiled gradient echo and balanced steady state free precession (bSSFP) are compared. In each case key relevant imaging parameters and vendor-specific terms are defined and explained.

Project description:This is the second of two reviews that is intended to cover the essential aspects of cardiovascular magnetic resonance (CMR) physics in a way that is understandable and relevant to clinicians using CMR in their daily practice. Starting with the basic pulse sequences and contrast mechanisms described in part I, it briefly discusses further approaches to accelerate image acquisition. It then continues by showing in detail how the contrast behaviour of black blood fast spin echo and bright blood cine gradient echo techniques can be modified by adding rf preparation pulses to derive a number of more specialised pulse sequences. The simplest examples described include T2-weighted oedema imaging, fat suppression and myocardial tagging cine pulse sequences. Two further important derivatives of the gradient echo pulse sequence, obtained by adding preparation pulses, are used in combination with the administration of a gadolinium-based contrast agent for myocardial perfusion imaging and the assessment of myocardial tissue viability using a late gadolinium enhancement (LGE) technique. These two imaging techniques are discussed in more detail, outlining the basic principles of each pulse sequence, the practical steps required to achieve the best results in a clinical setting and, in the case of perfusion, explaining some of the factors that influence current approaches to perfusion image analysis. The key principles of contrast-enhanced magnetic resonance angiography (CE-MRA) are also explained in detail, especially focusing on timing of the acquisition following contrast agent bolus administration, and current approaches to achieving time resolved MRA. Alternative MRA techniques that do not require the use of an endogenous contrast agent are summarised, and the specialised pulse sequence used to image the coronary arteries, using respiratory navigator gating, is described in detail. The article concludes by explaining the principle behind phase contrast imaging techniques which create images that represent the phase of the MR signal rather than the magnitude. It is shown how this principle can be used to generate velocity maps by designing gradient waveforms that give rise to a relative phase change that is proportional to velocity. Choice of velocity encoding range and key pitfalls in the use of this technique are discussed.

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MicroRNAs in cardiovascular disease: an introduction for clinicians.

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MicroRNAs in cardiovascular disease: an introduction for clinicians.

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