title: Emerging roles for RNA-binding proteins as effectors and regulators of cardiovascular disease.
abstract: The cardiovascular system comprises multiple cell types that possess the capacity to modulate their phenotype in response to acute or chronic injury. Transcriptional and post-transcriptional mechanisms play a key role in the regulation of remodelling and regenerative responses to damaged cardiovascular tissues. Simultaneously, insufficient regulation of cellular phenotype is tightly coupled with the persistence and exacerbation of cardiovascular disease. Recently, RNA-binding proteins such as Quaking, HuR, Muscleblind, and SRSF1 have emerged as pivotal regulators of these functional adaptations in the cardiovascular system by guiding a wide-ranging number of post-transcriptional events that dramatically impact RNA fate, including alternative splicing, stability, localization and translation. Moreover, homozygous disruption of RNA-binding protein genes is commonly associated with cardiac- and/or vascular complications. Here, we summarize the current knowledge on the versatile role of RNA-binding proteins in regulating the transcriptome during phenotype switching in cardiovascular health and disease. We also detail existing and potential DNA- and RNA-based therapeutic approaches that could impact the treatment of cardiovascular disease in the future.
authors.affiliation: Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2300RC, The Netherlands.|Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2300RC, The Netherlands.
authors.forename: Ruben G
authors.initials: RG
authors.lastname: de Bruin
authors.affiliation: Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2300RC, The Netherlands.|Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2300RC, The Netherlands.
authors.forename: Ton J
authors.initials: TJ
authors.lastname: Rabelink
authors.affiliation: Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2300RC, The Netherlands.|Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2300RC, The Netherlands.
authors.forename: Anton Jan
authors.initials: AJ
authors.lastname: van Zonneveld
authors.affiliation: Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2300RC, The Netherlands.|Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2300RC, The Netherlands.
authors.forename: Eric P
authors.initials: EP
authors.lastname: van der Veer
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000628:therapy; D042783:Endothelial Cells / Q000502:physiology; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D032383:Myocytes, Cardiac / Q000502:physiology; D010641:Phenotype; D012313:RNA / Q000235:genetics; D016601:RNA-Binding Proteins / Q000502:physiology*; D017154:Stromal Cells / Q000502:physiology; D059467:Transcriptome / Q000235:genetics
chemical_list: D016601:RNA-Binding Proteins; D012313:RNA
keywords: Alternative splicing; Cardiovascular disease; Post-transcriptional gene regulation; RNA therapeutics; RNA-binding proteins