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Thrombosis  2013 

Regulation of Vascular Function on Posttranscriptional Level

DOI: 10.1155/2013/948765

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Abstract:

Posttranscriptional control of gene expression is crucial for regulating plurality of proteins and functional plasticity of the proteome under (patho)physiologic conditions. Alternative splicing as well as micro (mi)RNA-mediated mechanisms play an important role for the regulation of protein expression on posttranscriptional level. Both alternative splicing and miRNAs were shown to influence cardiovascular functions, such as endothelial thrombogenicity and the vascular tone, by regulating the expression of several vascular proteins and their isoforms, such as Tissue Factor (TF) or the endothelial nitric oxide synthase (eNOS). This review will summarize and discuss the latest findings on the (patho)physiologic role of alternative splicing processes as well as of miRNAs on modulation of vascular functions, such as coagulation, thrombosis, and regulation of the vascular tone. 1. Introduction The expression of proteins and their isoforms is of immense importance for the induction as well as the control of (patho)physiologic functions in the vasculature, such as maintenance of the vessel wall homeostasis, blood coagulation, thrombosis, modulation of the vascular tone, and angiogenesis [1–8]. The differential protein and isoform expression is highly regulated on transcriptional as well as on posttranscriptional level. The regulatory factors and mechanisms of gene expression on transcriptional level were reviewed in detail elsewhere [9–11]. Therefore, this review will focus on the posttranscriptional expression regulation and the influence of these processes on vascular function. The modulation of gene expression on posttranscriptional level is essential for increasing and for regulating the diversity of proteins and their biologic functions under (patho)physiologic conditions [12, 13]. Alternative splicing and micro (mi)RNA-mediated processes are the most important mechanisms for the control of protein expression on posttranscriptional level [14, 15]. Moreover, both mechanisms were demonstrated to control vascular functions (see Tables 1 and 2), such as endothelial thrombogenicity and regulation of vascular tone, by modulating the expression of vascular proteins, such as Tissue Factor (TF) and endothelial nitric oxide synthase (eNOS) [4, 8, 16–19]. The following parts of the paper will briefly summarize the latest findings regarding the influence of alternative splicing and miRNAs on the expression and function of vascular factors, such as TF and eNOS. Table 1: Vascular functions of protein isoforms. Table 2: Vascular factors modulated by miRNAs. 2. The

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