Vascular Pharmacology 55 (2011) 59
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Introduction
MicroRNAs in vascular biology, an introduction to the Vascular Pharmacology Special Issue on microRNAs In their mature forms, microRNAs (miRNAs) are small RNA molecules able to post-transcriptionally inhibit the expression of a plethora of target genes, following the (partial) oligonucleotide base pairing between the short miRNA “seed sequence” and the 3'UTR region (and much less frequently the 5'UTR region) of the target messenger RNA (mRNA). The overall result of this miRNA–mRNA encounter is mRNA instability/degradation and/or inhibition of protein production. The interactions of a miRNA and its target genes are ultimately responsible for the miRNA function and they vary in different cells and tissues as well as in response to perturbation of the cellular mRNA transcripts pools, such as following pathological events. miRNAs have come into focus of biomedical science in the last few years and are now regarded as essential components of the fine mechanisms regulating all aspects of life, including development, physiology and pathology. miRNAs are additionally being investigated as disease biomarkers and therapeutic targets and miRNA-base therapeutics is progressing rapidly, also because of the good level of integration between academic and industrial scientists. This Vascular Pharmacology Special Issue on miRNAs is composed of seven review articles prepared by top-experts in the field of miRNA and vascular biology. Each of these articles provides relevant information in a specific area and the combination of the seven publications is expected to provide the reader with a good knowledge of the stateof-the-art of miRNAs research in the field of vascular biology. Two articles have targeted the role in miRNAs in vascular development. Santoro has focussed on in vivo vascular development, which he studied using the zebrafish model (Santoro, this issue), one of the first models to be employed for miRNA studies and now widely exploited by several miRNA vascular biology laboratories (Santoro, this issue; Lagos-Quintana et al., 2003). The concept of miRNA involvement in vascular development is further integrated by Howard et al, who focussed on miRNA commanding the maintenance of pluripotency in embryonic stem cell (ESC) and those vice versa implicated in vascular differentiation of cultured ESCs (Howard et al., this issue). Vascular development is strictly associated with the angiogenesis processes and several (but very possibly not all) miRNAs regulating angiogenesis have been already identified and named as “Angio-miRNAs” (Wang and Olson, 2009). Here, Caporali and myself have prepared an article discussing the role of miRNAs in angiogenesis, focusing, in particular, on post-ischemic neovascularization (Caporali and Emanueli, this issue). To complement this, Quintavalle C. et al, have analyzed the role of miRNAs in cancer angiogenesis and additionally acknowledged the existence of “Apopto-miRNAs”, namely miRNAs implicated with cell apoptotic death (Quintavalle et al., this
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issue). In addition, Quintavalle M. et al have reviewed recent advance regarding the involvement of miRNAs in arterial remodeling and atherosclerosis (Quintavalle et al., this issue). The role of miRNAs in vascular function and pathology is further described by Hartmann and Thum, who have summarized the latest insights in the identification of vascular-specific miRNAs and their targets and discussed how manipulation of these miRNAs could represent a novel therapeutic approach in the treatment of vascular dysfunction (Hartmann and Thum, this issue). Finally, Distefano et al have developed the concept that miRNAs which circulate in blood cells or serum/plasma are potential biomarkers of cardiovascular disease (Di Stefano et al., 2011). This is an emerging area of miRNA translational research and we expect to see many future studies aiming at identification and validation of miRNAs as diagnostic and/or prognostic marker of vascular disease and disease progression. As illustrated in this series, miRNAs are strictly implicated in vascular development, maintenance and disease. miRNA research in the vascular biology area is quite young, but the excitement that miRNAs have produced in the scientific community allows speculating for a fast growing of the knowledge and a promising translational future for miRNA diagnostics and therapeutics. References Santoro, M.M., this issue. “Fishing” for endothelial microRNA functions and dysfunction. Vascul. Pharmacol. Lagos-Quintana, M., et al., 2003. New microRNAs from mouse and human. RNA 9 (2), 175–179. Howard, L., et al., this issue. MicroRNAs regulating cell pluripotency and vascular differentiation. Vascul. Pharmacol. Wang, S., Olson, E.N., 2009. AngiomiRs—key regulators of angiogenesis. Curr. Opin. Genet. Dev. 19 (3), 205–211. Caporali, A., Emanueli, C., this issue. MicroRNA regulation in angiogenesis. Vascul. Pharmacol. Quintavalle, C., et al., this issue. “ApoptomiRs” in vascular cells: their role in physiological and pathological angiogenesis. Vascul. Pharmacol. Quintavalle, M., Condorelli, G., Elia, L., this issue. Arterial remodeling and atherosclerosis: miRNAs involvement. Vascul. Pharmacol. Hartmann, D., Thum, T., this issue. MicroRNAs and vascular (dys)function. Vascul. Pharmacol. Di Stefano, V., et al., 2011. microRNAs as peripheral blood biomarkers of cardiovascular disease. Vascul. Pharmacol.
Costanza Emanueli Laboratory of Vascular Pathology and Regeneration, School of Clinical Sciences-Regenerative Medicine Section, University of Bristol, Bristol, England, UK E-mail address:
[email protected]