33 research outputs found

    Cardiovascular extracellular microRNAs: emerging diagnostic markers and mechanisms of cell-to-cell RNA communication

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    Cardiovascular diseases are a leading cause of morbidity and mortality in Western societies. It is now well established that microRNAs (miRNAs) are determinant regulators in various medical conditions including cardiovascular diseases. The recent discovery that miRNAs, while associated with different carriers, can be exported out of the cell, has triggered a renewed interest to analyze the potential to use extracellular miRNAs as tools for diagnostic and therapeutic studies. Circulating miRNAs in biological fluids present a technological advantage compared to current diagnostic tools by virtue of their remarkable stability and relative ease of detection rendering them ideal tools for non-invasive and rapid diagnosis. Extracellular miRNAs also represent a novel form of inter-cellular communication by transferring genetic information from a donor cell to a recipient cell. This review briefly summarizes recent insights in the origin, function and diagnostic potential of extracellular miRNAs by focusing on a select number of cardiovascular diseases

    Cardiac regenerative medicine: At the crossroad of microRNA function and biotechnology

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    There is an urgent need to develop new therapeutic strategies to stimulate cardiac repair after damage, such as myocardial infarction. Already for more than a century scientist are intrigued by studying the regenerative capacity of the heart. While moving away from the old classification of the heart as a post-mitotic organ, and being inspired by the stem cell research in other scientific fields, mainly three different strategies arose in order to develop regenerative medicine, namely; the use of cardiac stem cells, reprogramming of fibroblasts into cardiomyocytes or direct stimulation of endogenous cardiomyocyte proliferation. MicroRNAs, known to play a role in orchestrating cell fate processes such as proliferation, differentiation and reprogramming, gained a lot of attention in this context the latest years. Indeed, several research groups have independently demonstrated that microRNA-based therapy shows promising results to induce heart tissue regeneration and improve cardiac pump function after myocardial injury. Nowadays, a whole new biotechnology field has been unveiled to investigate the possibilities for efficient, safe and specific delivery of microRNAs towards the heart

    Regulation of fetal gene expression in heart failure

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    AbstractDuring the processes leading to adverse cardiac remodeling and heart failure, cardiomyocytes react to neurohumoral stimuli and biomechanical stress by activating pathways that induce pathological hypertrophy. The gene expression patterns and molecular changes observed during cardiac hypertrophic remodeling bare resemblance to those observed during fetal cardiac development. The re-activation of fetal genes in the adult failing heart is a complex biological process that involves transcriptional, posttranscriptional and epigenetic regulation of the cardiac genome. In this review, the mechanistic actions of transcription factors, microRNAs and chromatin remodeling processes in regulating fetal gene expression in heart failure are discussed

    Non-coding RNA in control of gene regulatory programs in cardiac development and disease

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    Organogenesis of the vertebrate heart is a highly specialized process involving progressive specification and differentiation of distinct embryonic cardiac progenitor cell populations driven by specialized gene programming events. Likewise, the onset of pathologies in the adult heart, including cardiac hypertrophy, involves the reactivation of embryonic gene programs. In both cases, these intricate genomic events are temporally and spatially regulated by complex signaling networks and gene regulatory networks. Apart from well-established transcriptional mechanisms, increasing evidence indicates that gene programming in both the developing and the diseased myocardium are under epigenetic control by non-coding RNAs (ncRNAs). MicroRNAs regulate gene expression at the post-transcriptional level, and numerous studies have now established critical roles for this species of tiny RNAs in a broad range of aspects from cardiogenesis towards adult heart failure. Recent reports now also implicate the larger family of long non-coding RNAs (lncRNAs) in these processes as well. Here we discuss the involvement of these two ncRNA classes in proper cardiac development and hypertrophic disease processes of the adult myocardium. This article is part of a Special Issue entitled: Non-coding RNAs

    Antisense MicroRNA Therapeutics in Cardiovascular Disease: Quo Vadis?

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    Heart failure (HF) is the end result of a diverse set of causes such as genetic cardiomyopathies, coronary artery disease, and hypertension and represents the primary cause of hospitalization in Europe. This serious clinical disorder is mostly associated with pathological remodeling of the myocardium, pump failure, and sudden death. While the survival of HF patients can be prolonged with conventional pharmacological therapies, the prognosis remains poor. New therapeutic modalities are thus needed that will target the underlying causes and not only the symptoms of the disease. Under chronic cardiac stress, small noncoding RNAs, in particular microRNAs, act as critical regulators of cardiac tissue remodeling and represent a new class of therapeutic targets in patients suffering from HF. Here, we focus on the potential use of microRNA inhibitors as a new treatment paradigm for HF
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