Posttranscriptional adaptations of the vascular endothelium to hypoxia

Remarkable new advances have been made in the field of posttranscriptional gene regulation over recent years. These include the revelation of noncoding RNAs, such as microRNAs, antisense transcripts and their interactions with RNA-binding proteins (RBPs) in the context of both health and disease settings, such as hypoxia. In particular, these discoveries bear much relevance to the field of vascular biology, which historically has focused upon transcriptional processes. Thus, the contributions of these posttranscriptional gene regulatory mechanisms to vascular and endothelial biology represent a newer concept that warrants discussion.

Recent studies have revealed two emerging themes that are critical to endothelial/vascular biology and function. First is the functional integration between the microRNA pathway and the cellular hypoxic response, which, in addition to specific microRNAs, involves key components of the microRNA biogenesis machinery. A key concept here is the regulation of a master transcriptional programme through posttranscriptional mechanisms. The second major theme involves the dynamic interactions between RBPs, microRNAs and antisense RNAs. The condition-dependent collaborations and competitions between these different classes of posttranscriptional regulators reveal a critical layer of control for gene expression.

Taken together, these findings bear significant diagnostic and therapeutic implications for vascular disease.