Abstract
The novel protein ADTRP, identified and described by us in 2011, is androgen-inducible and regulates the expression and activity of Tissue Factor Pathway Inhibitor, the major inhibitor of the Tissue Factor-dependent pathway of coagulation on endothelial cells. Single-nucleotide polymorphisms in ADTRP associate with coronary artery disease and myocardial infarction, and deep vein thrombosis/venous thromboembolism. Some athero-protective effects of androgen could exert through up-regulation of ADTRP expression. We discovered a critical role of ADTRP in vascular development and vessel integrity and function, manifested through Wnt signaling-dependent regulation of matrix metalloproteinase-9. ADTRP also hydrolyses fatty acid esters of hydroxy-fatty acids, which have anti-diabetic and anti-inflammatory effects and can control metabolic disorders. Here we summarize and analyze the knowledge on ADTRP and try to decipher its functions in health and disease.
Highlights
The novel protein ADTRP, identified and described by Lupu and colleagues in 2011, is androgen-inducible and up-regulates the expression and activity of tissue factor pathway inhibitor (TFPI), the major inhibitor of the tissue factor (TF)-dependent pathway of coagulation on endothelial cells (EC)
We applied the method developed by Wren [32], namely the global meta-analysis (GAMMA) of over 3500 NCBI’s Gene Expression Omnibus (GEO) 2-channel human microarray datasets and we identified C6ORF105 as having a very high score of co-expression with TFPI [28]
Since MMP-9 and IL-8 are known to contribute to the development of human atherosclerotic plaques [60], we can speculate that, through its prominent role in vascular homeostasis ADTRP may be critically involved in pathologies that feature disruption of the vascular wall, such as coronary artery disease (CAD)/myocardial infarction (MI), deep vein thrombosis (DVT)/venous thromboembolism (VTE), sepsis, and cancer
Summary
The novel protein ADTRP (androgen-dependent TFPI-regulating protein), identified and described by Lupu and colleagues in 2011, is androgen-inducible and up-regulates the expression and activity of tissue factor pathway inhibitor (TFPI), the major inhibitor of the tissue factor (TF)-dependent pathway of coagulation on endothelial cells (EC). Endothelial dysfunction, including dysregulated production and activity of the enzymes and/or inhibitors that control coagulation and fibrinolysis, impact vascular homeostasis. This favors the development of pathologies involving disruption of the vascular wall, such as myocardial infarction (MI), deep vein thrombosis (DVT)/venous thromboembolism (VTE), sepsis, and cancer. Along the ten years from its discovery, a few labs tried to address the physio-pathologic role of ADTRP and a variety of potential functions emerged for ADTRP distinct from TFPI regulation. This review is aimed to bring together all the present knowledge about ADTRP in an attempt to open the field for the development of mechanistic studies designed to decipher the main function(s) of ADTRP in health and disease.
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