The decreased levels observed in IRE1 and the increased levels of p-IRE1 are also consistent with the activation of the UPR mechanism, since this not implies an increase in the protein levels but also the activation is possible through dimerization and autophosphorylation. XBP1 upregulation has been reported in studies analyzing hypoxic effects in mouse culture cardiomyocytes. All of these findings are consistent with the XBP1 activation in the UPR to increase the transcription of ER stress response genes. ATF6 is a ER transmembrane signaling protein that together with IRE1 and PERK are the major sensors of unfolded proteins of the ER. ATF6 is activated by dissociation of GRP78 and its translocation to the Golgi and to the nucleus, is responsible for transcriptional regulation of pro-survival genes following ER stress, inducing the expression of ER stress genes. We found that ATF6 was upregulated in both DCM and ICM patients, demonstrating that this ER stress pathway is highly important to activate the response during HF. All these results evidence the strong activation of UPR mechanism in HF patients that implies alterations in the levels of the majority of ER stress proteins. Due to the ER stress process, is probably that a MI-773 modification of the structure and shape of ER could occur in HF. The reticulons are a A 83-01 family of proteins that function mainly to stabilize the curvature of ER tubules. In this work, we analyzed three members of this family, Reticulon 1 and two isoforms of Reticulon 4. We found that Reticulon 1 is downregulated in DCM patients, whereas Nogo A and B were upregulated. Voeltz et al. have studied the effect of expression modification of reticulons in vitro and found that the downregulation of Reticulon 1 under stress conditions produces changes in the peripheral ER through the formation of membrane sheets; when the reticulons are overexpressed, tubule formation increases. These changes in the protein levels of reticulons may alter the stabilization of the ER curvature, conferring it a different structure. Nevertheless, none studies have examined this relationship in heart disease; however the findings shown in this study strongly suggest that vital functions of the ER rely on its morphological integrity.