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.
Highlights
The expression of proteins and their isoforms is of immense importance for the induction as well as the control ofphysiologic functions in the vasculature, such as maintenance of the vessel wall homeostasis, blood coagulation, thrombosis, modulation of the vascular tone, and angiogenesis [1,2,3,4,5,6,7,8]
There is a great discrepancy between the number of estimated protein-coding genes in the human genome and the number of generated proteins [20]. posttranscriptional expression modulation via alternative splicing as well as miRNAs-mediated control is a major contributor to this immense increase in protein diversity [20, 21]
We found that increased expression of eNOS13A, B, and C diminished the Nitric oxide (NO) generation in proinflammatory-induced human endothelial cells [4]
Summary
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 [1,2,3,4,5,6,7,8]. The regulatory factors and mechanisms of gene expression on transcriptional level were reviewed in detail elsewhere [9,10,11]. Alternative splicing and micro (mi)RNA-mediated processes are the most important mechanisms for the control of protein expression on posttranscriptional level [14, 15]. 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, 16,17,18,19]. 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
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