TNF-α-mediated adhesion of monocytes to endothelial cells—The role of ephrinA1

Ende, Georg; Poitz, David M.; Wiedemann, Elisa; Augstein, Antje; Friedrichs, Jens; Giebe, Sindy; Weinert, Sönke; Werner, Carsten; Strasser, Ruth H.; Jellinghaus, Stefanie

doi:10.1016/j.yjmcc.2014.10.010

Cited by 33 publications

(27 citation statements)

References 44 publications

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“…Cultivation occurred in RPMI-1640 (Thermo Fisher Scientific, Waltham, MA, USA) containing 10% fetal calf serum. Primary human monocytes were isolated from buffy coats by a two-step density gradient centrifugation and cultured as described previously [36]. Human microvascular endothelial cells (HMEC-1, ATCC# CRL-3243) were cultured in Endothelial Cell Growth Medium MV2 (PromoCell, Heidelberg, Germany).…”

Section: Methodsmentioning

confidence: 99%

Cigarette smoke extract counteracts atheroprotective effects of high laminar flow on endothelial function

et al. 2017

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Tobacco smoking and hemodynamic forces are key stimuli in the development of endothelial dysfunction and atherosclerosis. High laminar flow has an atheroprotective effect on the endothelium and leads to a reduced response of endothelial cells to cardiovascular risk factors compared to regions with disturbed or low laminar flow. We hypothesize that the atheroprotective effect of high laminar flow could delay the development of endothelial dysfunction caused by cigarette smoking. Primary human endothelial cells were stimulated with increasing dosages of aqueous cigarette smoke extract (CSEaq). CSEaq reduced cell viability in a dose-dependent manner. The main mediator of cellular adaption to oxidative stress, nuclear factor erythroid 2-related factor 2 (NRF2) and its target genes heme oxygenase (decycling) 1 (HMOX1) or NAD(P)H quinone dehydrogenase 1 (NQO1) were strongly increased by CSEaq in a dose-dependent manner. High laminar flow induced elongation of endothelial cells in the direction of flow, activated the AKT/eNOS pathway, increased eNOS expression, phosphorylation and NO release. These increases were inhibited by CSEaq. Pro-inflammatory adhesion molecules intercellular adhesion molecule-1 (ICAM1), vascular cell adhesion molecule-1 (VCAM1), selectin E (SELE) and chemokine (C-C motif) ligand 2 (CCL2/MCP-1) were increased by CSEaq. Low laminar flow induced VCAM1 and SELE compared to high laminar flow. High laminar flow improved endothelial wound healing. This protective effect was inhibited by CSEaq in a dose-dependent manner through the AKT/eNOS pathway. Low as well as high laminar flow decreased adhesion of monocytes to endothelial cells. Whereas, monocyte adhesion was increased by CSEaq under low laminar flow, this was not evident under high laminar flow.This study shows the activation of major atherosclerotic key parameters by CSEaq. Within this process, high laminar flow is likely to reduce the harmful effects of CSEaq to a certain degree. The identified molecular mechanisms might be useful for development of alternative therapy concepts.

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Section: Methodsmentioning

confidence: 99%

Cigarette smoke extract counteracts atheroprotective effects of high laminar flow on endothelial function

et al. 2017

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“…It is acknowledged that Ephrin family members are involved in atherosclerotic related processes, like among others leukocyte chemotaxis, adhesion, and migration, and regulation of atherosclerotic inflammation 12‐14,24 . This is not surprising since EPHA2, EPHA8, and EPHB2, are located within the murine Athsq1 atherosclerosis susceptibility locus, 25 which is highly homologous to the premature myocardial infarction susceptibility locus in human 18 that similarly contains EPHA2, EPHA8, and EPHB2.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, NGCs have been implicated in leukocyte adhesion and migration, which implies that NGCs are crucial in the initial steps of atherogenesis 10 . Specifically, several studies have shown that members of the Ephrin family are involved in atherosclerosis related processes 10‐15 …”

Section: Introductionmentioning

confidence: 99%

EPH receptor B2 stimulates human monocyte adhesion and migration independently of its EphrinB ligands

Vreeken

Bruikman

Cox

et al. 2020

Journal of Leukocyte Biology

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The molecular basis of atherosclerosis is not fully understood and mice studies have shown that Ephrins and EPH receptors play a role in the atherosclerotic process. We set out to assess the role for monocytic EPHB2 and its Ephrin ligands in human atherosclerosis and show a role for EPHB2 in monocyte functions independently of its EphrinB ligands. Immunohistochemical staining of human aortic sections at different stages of atherosclerosis showed that EPHB2 and its ligand EphrinB are expressed in atherosclerotic plaques and that expression proportionally increases with plaque severity. Functionally, stimulation with EPHB2 did not affect endothelial barrier function, nor did stimulation with EphrinB1 or EphrinB2 affect monocyte‐endothelial interactions. In contrast, reduced expression of EPHB2 in monocytes resulted in decreased monocyte adhesion to endothelial cells and a decrease in monocyte transmigration, mediated by an altered morphology and a decreased ability to phosphorylate FAK. Our results suggest that EPHB2 expression in monocytes results in monocyte accumulation by virtue of an increase of transendothelial migration, which can subsequently contribute to atherosclerotic plaque progression.

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“…It is commonly known that the blood monocytes are first recruited to enter the intima of larger artery and then differentiate into macrophages, which uptake the modified LDL and finally develop into foam cells, a hallmark of the early stage of atherosclerosis [7]. So far, there are many reports suggesting that TNF-α enhances monocytes to adhere to endothelial cells [36][37][38][39]. Here, we treated monocytes with proinflammatory factor TNF-α or its inducer LPS and found that the monocytes activated by excess TNF-α in the blood have already gained the potential to adhere to endothelial cells, uptake oxLDL, and then directly form CE-laden cells.…”

Section: Discussionmentioning

confidence: 99%

Excess TNF-α in the blood activates monocytes with the potential to directly form cholesteryl ester-laden cells

Zhu

Lei

Zhu

et al. 2015

ABBS

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The tumor necrosis factor-α (TNF-α) and monocytic cells play a critical role in the development of atherosclerosis, which is the major cause of coronary heart disease (CHD). In this work, we investigated the effect of excess TNF-α on monocytes in the blood and found that blood monocytes from the CHD patients had the potential to directly form cholesteryl ester (CE)-laden cells under the in vitro incubation with oxLDL. The plasma levels of proinflammatory cytokines, such as TNF-α, interleukin 6 (IL-6), and C reactive protein (CRP), in the CHD patients were significantly higher than those in the control healthy volunteers. However, only the plasma level of TNF-α, but not of IL-6 or CRP, is positively correlated with the potential of blood monocytes to directly form CE-laden cells. By using human blood monocytes and monocytic THP-1 cells, the activating effect of TNF-α on the formation of the CE-laden cells was demonstrated, which could be specifically blocked by the anti-TNF-α antibody. Furthermore, it was also revealed that TNF-α could boost adhesion and oxLDL uptake of the monocytes by enhancing the expression of the functional adhesion molecules and scavenger receptors, respectively. Finally, the results of in vivo and in vitro experiments with a mouse model confirmed that excess TNF-α in the blood activates monocytes with the potential to directly form CE-laden cells. These data demonstrate that excess TNF-α in the blood is the primary trigger for the development of atherosclerosis and CHD.

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TNF-α-mediated adhesion of monocytes to endothelial cells—The role of ephrinA1

Cited by 33 publications

References 44 publications

Cigarette smoke extract counteracts atheroprotective effects of high laminar flow on endothelial function

Cigarette smoke extract counteracts atheroprotective effects of high laminar flow on endothelial function

EPH receptor B2 stimulates human monocyte adhesion and migration independently of its EphrinB ligands

Excess TNF-α in the blood activates monocytes with the potential to directly form cholesteryl ester-laden cells

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TNF-α-mediated adhesion of monocytes to endothelial cells—The role of ephrinA1

Cited by 33 publications

References 44 publications

Cigarette smoke extract counteracts atheroprotective effects of high laminar flow on endothelial function

Cigarette smoke extract counteracts atheroprotective effects of high laminar flow on endothelial function

EPH receptor B2 stimulates human monocyte adhesion and migration independently of its EphrinB ligands

Excess TNF-&alpha; in the blood activates monocytes with the potential to directly form cholesteryl ester-laden cells

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Excess TNF-α in the blood activates monocytes with the potential to directly form cholesteryl ester-laden cells