Modification of proteins secreted by endothelial cells during modeled low gravity exposure

Abstract

The exposure of the human body to microgravity, conditions that occurs during space flights, causes significant changes in the cardiovascular system. Many cell types have been involved in these changes, and the endothelium seems to play a major role. In endothelial cells (EC), it has been shown that modeled low gravity impairs nitric oxide synthesis, cell adhesion, extracellular matrix composition, cytoskeleton organization, cytokines, and growth factors secretion. Nevertheless, detailed analysis of EC physiological changes induced by microgravity exposure is still lacking. Secretome analysis is one of the most promising approaches for the identification of biomarkers directly related to the physiopathological cellular state. In this study, we analyzed in details the modifications of EC secretome by using umbilical vein endothelial (HUVE) cells exposed to modeled low gravity conditions. By adopting a two-dimensional (2-D) proteomic approach, in conjunction with a technique for the compression of the dynamic range of proteins, we observed that modeled low gravity exposure of HUVE cells affected the secretion of proteins involved in the regulation of cytoskeleton assembly. Moreover, by using Luminex® suspension array systems, we found that the low gravity condition decreased in ECs the secretion of some key pro-inflammatory cytokines, including IL-1α and IL-8, and of the pro-angiogenic factor bFGF. On the contrary, microgravity increase the secretion of two chemokines (Rantes and Eotaxin), involved in leukocytes recruitment.

The Effects of Weightlessness on the Human Organism and Mammalian Cells

“…It was confirmed that the secretion of bFGF is reduced, when the secretion of IL-1 and IL-8 is reduced. A significant increase in the secretion of the chemokines Rantes and Eotaxin were observed; both of them play a role in leukocyte recruitment [118]. The latest findings by Kang et al on the effect of simulated microgravity on microvascular endothelial cells show an induction of apoptosis.…”

Effects of Simulated Microgravity on Human Umbilical Vein Endothelial Cell Angiogenesis and Role of the PI3K-Akt-eNOS Signal Pathway

“…Recent reports have indicated that endothelial cells (ECs) on the interior surfaces of vessels are highly sensitive to microgravity and undergo morphological and functional changes under these conditions [4]–[6]. Because ECs are key to vascular function, inflammation, and angiogenesis, endothelial dysfunction is likely to be one important factor of the basis of weightlessness-induced cardiovascular deconditioning [7], [8]. For this reason, several studies have been devoted to the means by which microgravity affects endothelial cell functions.…”

“…Morbidelli et al obtained opposite results in porcine aortic ECs [6]. The expression of many angiogenic molecules, such as nitric oxide (NO), vascular endothelial cell growth factor (VEGF) and endothelin-1 are modified under microgravity conditions, which also indicates that microgravity conditions may influence angiogenesis [5], [8], [11].…”

Glycoproteomic Analysis of the Secretome of Human Endothelial Cells

“…Previous proteomics studies (7–13), including one by our group (8), have investigated the secretome of unstimulated human umbilical vein ECs (HUVECs), the most widely used ECs in cardiovascular research. Only two studies have explored the secretome of HUVECs upon activation by shear stress (10) or with statin treatment (13) thus far.…”