The basis of these major consequences of the Asp47Tyr mutation remains to be defined. However, it is interesting to note that the Asp47Tyr mutation involves a residue on the surface of SEDLIN that could possibly lead to loss of postulated or known interactions with other proteins, such as: the soluble N-ethylmaleimide-sensitive factor attachment proteins, which are also involved in the vesicle transport pathway; or the intracellular chloride channels CLIC1 and CLIC2, respectively. In Alprostadil summary, our results show that SEDLIN is a nuclear and cytoplasmic protein that forms homodimers. Moreover, 3 of the SEDLIN missense mutations and 1 nonsense mutation located within the hydrophobic core and associated with SEDT in patients lead to a loss of interactions with the transcription factors MBP1, PITX1 and SF1. Others and we have described agonistic autoantibodies against the a1-AR in hypertensive patients. We found earlier that a1-AR-autoantibody immunoadsorption reduced blood pressure in patients with refractory hypertension. In that study, rabbit or patient-derived a1AAR-autoantibodies were purified with chromatography and characterized by epitope mapping and surface plasmon resonance measurements. Phospholipase A2 group IIA and L type calcium channel genes were upregulated in cardiomyocytes and VSMC after stimulation with both purified antibodies from patients and from rabbit. We showed that patient and rabbit a1A-AR-antibodies result in protein kinase C alpha activation and transient Fenticonazole Nitrate extracellular-related kinase phosphorylation. The antibodies also exerted acute effects on intracellular Ca2+ in cardiomyocytes and contracted mesentery artery segments. In a proof-of-concept study involving the b1AR, Jahns et al immunized rats and showed that agonistic autoantibodies caused idiopathic dilated cardiomyopathy in the same rats. Furthermore, passive transfer also caused disease. The rats developed agonistic antibodies. Tail-cuff systolic blood pressure was not changed. The investigators described cardiac hypertrophy, increase in the collagen deposition, c-jun, and matrix metalloproteinase 2 expressions in the heart.