Pin1 in cardiovascular dysfunction: A potential double-edge role

Our lab focused on the structural and functional properties of Pin1, which is the only known cis-trans isomerase regulating pSer/pThr-Pro motifs in proteins and facilitates various signaling pathways. We are lucky enough to read the article, contributed by Costantino et al. in your esteemed journal, on the role of Pin1 in diabetes-induced vascular dysfunction. Pin1 regulates the production of nitric oxide (NO), which is a key physiological stimulator of blood vessels and promotes vascular relaxation responses significantly. However, the regulation of cardiovascular diseases by Pin1 is somewhat controversial.

We compared the recent studies that support the down-regulation, as well as up-regulation, of NO production by Pin1 and tried to explore the underlying molecular mechanisms. We especially compared the different regulations of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) by Pin1, which is potentially the major reason leading to the controversial role of Pin1. Interestingly, the regulation of both eNOS and iNOS by Pin1 involves a double-edge effect, positively and negatively, contributing to paradoxical Pin1 functions in different animal models and cell lines. The extremely complex Pin1-regulated signaling networks might further exacerbate distinct cellular responses in vivo and influence NO production.

Pin1 plays a dual role, both positive and negative, in regulating NO production and in mediating the pathogenesis of cardiovascular diseases. Pin1 functions may vary a lot under different circumstances. Future investigations should focus on eNOS as well as iNOS in order to increase authenticity and accuracy of results.