title: Modulation of endothelial cell migration by ER stress and insulin resistance: a role during maternal obesity?
abstract: Adverse microenvironmental stimuli can trigger the endoplasmic reticulum (ER) stress pathway, which initiates the unfolded protein response (UPR), to restore protein-folding homeostasis. Several studies show induction of ER stress during obesity. Chronic UPR has been linked to different mechanisms of disease in obese and diabetic individuals, including insulin resistance (IR) and impaired angiogenesis. Endothelial cell (EC) migration is an initial step for angiogenesis, which is associated with remodeling of existing blood vessels. EC migration occurs according to the leader-follower model, involving coordinated processes of chemotaxis, haptotaxis, and mechanotaxis. Thus, a fine-tuning of EC migration is necessary to provide the right timing to form the required vessels during angiogenesis. ER stress modulates EC migration at different levels, usually impairing migration and angiogenesis, although different effects may be observed depending on the tissue and/or microenvironment. In the context of pregnancy, maternal obesity (MO) induces IR in the offspring. Interestingly, several proteins associated with obesity-induced IR are also involved in EC migration, providing a potential link with the ER stress-dependent alterations observed in obese individuals. Different signaling cascades that converge on cytoskeleton regulation directly impact EC migration, including the Akt and/or RhoA pathways. In addition, ER is the main intracellular reservoir for Ca(2+), which plays a pivotal role during EC migration. Therefore, ER stress-related alterations in Ca(2+) signaling or Ca(2+) levels might also produce distorted EC migration. However, the above findings have been studied in the context of adult obesity, and no information has been reported regarding the effect of MO on fetal EC migration. Here we summarize the state of knowledge about the possible mechanisms by which ER stress and IR might impact EC migration and angiogenesis in fetal endothelium exposed to MO during pregnancy.
authors.affiliation: Cellular and Molecular Physiology Laboratory, Division of Obstetrics and Gynecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile Santiago, Chile.
authors.forename: Pablo J
authors.initials: PJ
authors.lastname: Sáez
authors.affiliation: Cellular and Molecular Physiology Laboratory, Division of Obstetrics and Gynecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile Santiago, Chile.
authors.forename: Roberto
authors.initials: R
authors.lastname: Villalobos-Labra
authors.affiliation: Cellular and Molecular Physiology Laboratory, Division of Obstetrics and Gynecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile Santiago, Chile ; Facultad de Ciencia, Universidad San Sebastián Santiago, Chile ; Advanced Center for Chronic Diseases, Faculty of Chemical and Pharmaceutical Sciences and Faculty of Medicine, University of Chile Santiago, Chile.
authors.forename: Francisco
authors.initials: F
authors.lastname: Westermeier
authors.affiliation: Cellular and Molecular Physiology Laboratory, Division of Obstetrics and Gynecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile Santiago, Chile ; University of Queensland Centre for Clinical Research, Faculty of Medicine and Biomedical Sciences, University of Queensland Herston, QL, Australia ; Faculty of Pharmacy, Universidad de Sevilla Sevilla, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Sobrevia
authors.affiliation: Cellular and Molecular Physiology Laboratory, Division of Obstetrics and Gynecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile Santiago, Chile.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Farías-Jofré
keywords: Akt; RhoA; Scrib; cytoskeleton; mesenchymal migration; polarization; unfolded protein response