Abstract
Alternative splicing, a driver of posttranscriptional variance, differs from canonical splicing by arranging the introns and exons of an immature pre-mRNA transcript in a multitude of different ways. Although alternative splicing was discovered almost half a century ago, estimates of the proportion of genes that undergo alternative splicing have risen drastically over the last two decades. Deep sequencing methods and novel bioinformatic algorithms have led to new insights into the prevalence of spliced variants, tissue-specific splicing patterns and the significance of alternative splicing in development and disease. Thus far, the role of alternative splicing has been uncovered in areas ranging from heart development, the response to myocardial infarction to cardiac structural disease. Circular RNAs, a product of alternative back-splicing, were initially discovered in 1976, but landmark publications have only recently identified their regulatory role, tissue-specific expression, and transcriptomic abundance, spurring a renewed interest in the topic. The aim of this review is to provide a brief insight into some of the available findings on the role of alternative splicing in cardiovascular disease, with a focus on atherosclerosis, myocardial infarction, heart failure, dilated cardiomyopathy and circular RNAs in myocardial infarction.
Highlights
Transcribed immature pre-mRNA transcripts are further altered through the splicing process
Modern high-throughput methods have delivered new insights regarding the frequency of alternative splicing events in humans, which have been found to occur in most multiple-exon genes [4]
This review aims to present some of the recent discoveries which focus on the role of alternative splicing in cardiovascular disease (CVD)
Summary
Transcribed immature pre-mRNA transcripts are further altered through the splicing process. The proangiogenic splicing shift induced increased apoptosis of macrophages and proliferation of endothelial cells [34] They concluded that alternative splicing pathways, and the splicing variant VEGF165 may play a role in the formation of atherosclerotic plaques. VEGF165b, which is formed through alternative splice site selection on exon 8, induces an antiangiogenic phenotype in macrophages, which, as shown by Ganta et al, impairs the recovery of perfusion of ischemic muscle in an animal model of limb ischemia [35] It is not always one specific alternative splicing variant that plays an important role in the pathogenesis of a disease, but sometimes, as shown in the example of fibronectin in a study by Babaev et al the act of alternative splicing itself, with two or more resulting products whose combined effect differs from both individual ones. These findings are not in direct conflict with the initially reported results due to the use of a different model whose primary use is studying diabetes-related endothelial dysfunction, they warrant further research on the role of FibronectinEDA in atherosclerosis
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