Table 1.

Pin1 molecular targets in circulating cells: expanding its role to vascular inflammation.

Cell Types	Molecular Targets	Roles	References
T Lymphocytes	A+U-rich RNA-binding factor (AUF1)	Pin1 mediates the association of AUF1 with GM-CSF mRNA, which determines the rate of decay by the exosome.	[34]
T cells	The transcription factor PU.1	Differentiation	[35]
Eosinophils	The transcription factor X box-binding protein 1 (XBP1) and Interleukin-1 receptor (IL1R)-associated kinase 4 (IRAK4) AUF1 Heterogeneous nuclear ribonucleoprotein C (hnRNP C)	Toll-like receptor 7 (TLR7)-induced IFN expression. Pin1 mediates association of AUF1 with granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA, accelerating the rate of decay. Pin1 mediates association of hnRNP C with GM-CSF mRNA, decelerating the rate of decay.	[32,36]
Neutrophils	p47phox (phox: phagocyte oxidase), the phagocyte NADPH oxidase/NOX2 organizer	Pin1 binds to p47phox, inducing conformational changes that facilitate p47phox phosphorylation by protein kinase C (PKC), and results in NADPH oxidase hyperactivation. Pin1 mediates TNF-α–induced neutrophil NADPH oxidase priming and reactive oxigen species hyperproduction via specific binding to p47phox.	[37,38]
Monocytes	The transcription factors RUNX1 and PU.1	Pin1 enhances Runx1 activity and represses PU.1 transcription.	[39]
Macrophages	p38MAPK (p38 mitogen activated protein kinase)	In LPS-induced septic shock, Pin1 indirectly regulates p38MAPK-mediated NLRP3 (NLR Family Pyrin Domain Containing 3) inflammosome.	[40]
Megakaryocytes	p-tau	The interaction between Pin1 and p-tau promotes microtubule assembly and proplatelet formation.	[41]
Endothelial cells	Tissue factor (TF)	The interaction between Pin1 and TF results in increased protein half-life and pro-coagulant activity.	[42]
	NF-Kβ	Deposition of atherosclerotic plaques.	[10]
	eNOS	Pin1 physically interacts with eNOS and inhibits eNOS activation and NO production in BAECs.	[9,14]
	eNOS	Pin1 binds eNOS, promotes eNOS Ser116 dephosphorylation, and increases NO production.	[13]
	iNOS	Pin1 interacts with iNOS and regulates NO production.	[8]
Vascular endothelial cells	p53	Pin1 promotes heat stress-induced localization of p53 to mitochondria.	[43]
Vascular smooth muscle cell (VSMC)	p53, p21, Gadd45a, p-pRb, p65, and cyclins	In atherosclerotic VSMC Pin1 modulates cellular senescence.	[44]
Vascular smooth muscle cell (VSMC)	The transcription factor Bromine domain protein 4, BRD4	Pin1 binds BRD4 and regulates proliferation and migration of VSMC.	[45]