Review focus on the role of microRNA in cardiovascular biology and disease

T Thum, M Mayr - Cardiovascular Research, 2012 - academic.oup.com
Cardiovascular Research, 2012academic.oup.com
MicroRNAs (miRNAs; miR) are emerging therapeutic targets in a broad range of diseases,
including cardiovascular disease. There are many programmes at the international level
currently investigating the suitability of miRNA therapeutics for clinical purposes, and these
new developments may potentially result in a novel armada of more powerful and
mechanism-oriented therapeutics. It is now well accepted that miRNAs represent critical
regulators of cardiovascular function. 1, 2 Initial reports about the role of miRNAs in …
MicroRNAs (miRNAs; miR) are emerging therapeutic targets in a broad range of diseases, including cardiovascular disease. There are many programmes at the international level currently investigating the suitability of miRNA therapeutics for clinical purposes, and these new developments may potentially result in a novel armada of more powerful and mechanism-oriented therapeutics. It is now well accepted that miRNAs represent critical regulators of cardiovascular function. 1, 2 Initial reports about the role of miRNAs in cardiovascular development 3 and disease 4 have stimulated tremendous interest, resulting in a substantial gain of knowledge about miRNAs in the cardiovascular system. This almost unprecedented speed of development can probably be explained by the direct translational impact of miRNA research: the suitability of miRNAs to serve as potential prognostic biomarkers 1, 5 and as therapeutic targets 6, 7 for cardiovascular disease is intriguing and justifies our initial excitement about non-coding RNAs. This review focus issue of Cardiovascular Research summarizes novel and exciting aspects of miRNA-based mechanisms, diagnostics, and therapeutic developments for cardiovascular diseases. To start with, it is important to note that the fast pace of miRNA research has required the development of many new techniques and methods. Thus, the review article by Dangwal et al. 8 mainly focuses on techniques and methods in cardiovascular miRNA research. In essence, the authors describe new methods to screen for miRNA expression and to identify and validate miRNA targets. They also address advances in the manipulation of miRNA expression both in vitro and in vivo, a prerequisite for studies using miRNA-based therapeutics. Surprisingly, miRNAs also exist extracellularly, where they may serve as biomarkers for disease in the circulation and other bodily fluids. This aspect is introduced by Dangwal et al. 8 and in more detail by Zampetaki et al. 9 The latter group points out that most circulating miRNAs are probably derived from blood cells, and miRNA patterns in the circulation are therefore often highly correlated. Thus, miRNAs should not be studied in isolation but rather within the context of the overall miRNA networks, and the assessment of their biomarker potential requires high analytical standards. Another important aspect is the ‘packaging’of circulating miRNAs, and thus, the original article of Diehl et al. 10 about microparticles as miRNA carriers provides new insights in this field. In addition to technological advances and the utility of miRNAs as biomarkers, there are exciting new developments in the understanding of the molecular mechanisms of how miRNAs are involved in cardiovascular disease processes. The review of Da Costa Martins and De Windt 11 gives an update on the role of miRNAs and their respective targets in cardiac growth and outlines the delicate balance of protagonist and antagonist miRNAs within the context of cardiac hypertrophy. The original paper by Han et al. 12 shows novel data concerning miRNA-mediated regulation of the cardiomyocyte-relevant transcription factor GATA4 and pressure-induced cardiac hypertrophy. It is apparent that the non-cardiomyocyte fraction also plays an important role in cardiac function as well as disease; Tijsen et al. 13 review the role of miRNAs in non-cardiomyocytes, especially cardiac fibroblasts, endothelial cells, and immune cells in response to myocardial stress.
It is also of great interest how cardiovascular risk factors might affect miRNA signalling. Indeed, diabetes is one of the most important risk factors for the development of cardiovascular diseases, and …
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