Modulazione degli effetti dello stress del reticolo endoplasmatico da parte dell'inibitore di PTP1B Claramina, in modelli murini e endoteliali

Protein tyrosine phosphatase 1 B (PTP1B) is involved in the dephosphorylation and regulation of several pathways in different tissues. Its inhibition seems to exert protective effects in various diseases, including diabetes, heart failure and atherosclerosis. In the past few years, it has been discovered that PTP1B contributes to endoplasmic reticulum (ER) stress, a physio-pathological condition that occurs upon accumulation of unfolded proteins and aims to couple ER-folding capacity with the increased demand. Since ER stress is known to be linked to endothelial dysfunction, we hypothesise that PTP1B represents a connection between these two processes. To demonstrate this, the induction of ER stress in endothelial cells and mice is obtained with Tunicamycin and parameters such as cell viability, nitrite production in supernatant of cultured cells and flow-mediated dilation of cannulated mesenteric arteries are assessed. The subsequent PTP1B inhibition by Claramine, a novel and specific inhibitor for this phosphatase, allows the negative effects of ER stress on both cellular and murine model, to be rescued. Even if incomplete, the results of this study support the idea that the attenuation of endothelial dysfunction by PTP1B inhibition may be mediated by a reduction of ER stress. This relationship should be investigated more deeply, since the inhibition of PTP1B could represent a protective mechanism for the maintenance of endothelial function in cardiovascular diseases.