Dabigatran: its protective effect against endothelial cell damage by oxysterol

Gorzelak-Pabiś, Paulina; Broncel, Marlena; Pawlos, Agnieszka; Wojdan, Katarzyna; Gajewski, Adrian; Chałubiński, Maciej; Woźniak, Ewelina

doi:10.1016/j.biopha.2022.112679

Cited by 6 publications

(8 citation statements)

References 26 publications

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“…The deterioration of the endothelial cells’ integrity exposed to 25-OHC could not have been caused by the decrease in cellular viability, because neither 25-hydroxycholesterol nor empagliflozin, canagliflozin, or dapagliflozin influenced the endothelial viability ( Table 3 ). 25-OHC, which is an oxidized form of cholesterol, acts as a proatherogenic stimuli and exerts a variety of effects in endothelial cells, including promoting inflammation, increasing oxidative stress, and affecting endothelial barrier integrity [ 10 , 22 ]. The interruption of endothelial integrity in response to proatherogenic stimuli is a crucial moment in atherogenesis, and VE-cadherin is the leading protein maintaining endothelial integrity [ 8 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…25-hydroxycholesterol (25-OHC) is an oxidized form of cholesterol that takes part in the build-up of atherosclerotic plaques [ 9 ]. In our previous studies, we have observed that 25-OHC impairs endothelial integrity and leads to increased permeability [ 10 ]. The integrity of the endothelial layer is maintained by proteins, which form tight and adherens inter-cellular junctions.…”

Section: Introductionmentioning

confidence: 99%

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SGLT2 Inhibitors May Restore Endothelial Barrier Interrupted by 25-Hydroxycholesterol

et al. 2023

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SGLT2 (Sodium-glucose Cotransporter-2) inhibitors are newer glucose-lowering drugs with many cardiovascular benefits that are not fully understood yet. Endothelial integrity plays a key role in cardiovascular homeostasis. 25-hydroxycholesterol (25-OHC), which is a proatherogenic stimuli that impairs endothelial barrier functions. VE-cadherin is an endothelial-specific protein crucial in maintaining endothelial integrity. The aim of this study was to assess the influence of SGLT2i on the integrity of endothelial cells interrupted by 25-OHC. We also aimed to evaluate whether this effect is associated with changes in the levels of VE-cadherin. We pre-incubated HUVECs with 10 μg/mL of 25-hydroxycholesterol (25-OHC) for 4 h and then removed it and incubated endothelial cells with 1 μM of empagliflozin, 1 μM canagliflozin, or 1 μM dapagliflozin for 24 h. The control group included HUVECs cultured with the medium or with 25-OHC 10 μg/mL. The integrity of endothelial cells was measured by the RTCA-DP xCELLigence system, and VE-cadherin was assessed in confocal microscopy. Our results show that SGLT2 inhibitors significantly increase endothelial integrity in comparison to medium controls, and they improve endothelial cell integrity interrupted by 25-OHC. This effect is associated with significant improvements in VE-cadherin levels. SGLT2i: empagliflozin, canagliflozin, and dapagliflozin have a beneficial effect on the endothelial cell integrity and VE-cadherin levels reduced by 25-OHC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

SGLT2 Inhibitors May Restore Endothelial Barrier Interrupted by 25-Hydroxycholesterol

et al. 2023

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“…DOAC-related enhancement of cell growth is debatable. Studies are showing that DOACs promote cell growth and proliferation (Wu et al, 2015;Sanada et al, 2016;Shi et al, 2018;Álvarez et al, 2018;Almengló et al, 2020), while in other studies no such effect was found (Woźniak et al, 2020;Gorzelak-Pabis et al, 2021;Gorzelak-Pabiś et al, 2022a). These contradictory effects may uncover real differences or be the result of different experimental settings.…”

Section: Figurementioning

confidence: 97%

“…Stimulation of HUVECs with 25-OHC caused downregulation of transforming growth factor beta 1 (TGFB1) and IL-37, and upregulation of IL-18, IL-23, and IL-35, which were counterbalanced when ECs were pre-incubated with rivaroxaban or dabigatran. Thus, both drugs exert anti-inflammatory properties (Gorzelak-Pabiś et al, 2022b). The same team also looked into the effects of dabigatran and rivaroxaban on DNA oxidative damage in HUVECs induced by 25-OHC.…”

Section: Comparative Studies Of Doacsmentioning

confidence: 99%

“…Atherosclerosis can be characterized as a chronic inflammatory disease of the vasculature, while there is a connection between atherosclerosis and disturbed hemostasis. In this notion, Gorzelak-Pabiś et al (2022a) investigated the effects of dabigatran in an in vitro model of chronic atherosclerosis using 25-hydroxycholesterol (25-OHC)-induced human umbilical vein endothelial cells (HUVECs). Dabigatran reversed all oxysterol-induced effects.…”

Section: In Vitro Experiments Using Doacs On Ecsmentioning

confidence: 99%

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Distinct pleiotropic effects of direct oral anticoagulants on cultured endothelial cells: a comprehensive review

Atzemian,

Kareli,

Ragia

et al. 2023

Front. Pharmacol.

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Direct Oral Anticoagulants (DOACs) have simplified the treatment of thromboembolic disease. In addition to their established anticoagulant effects, there are indications from clinical and preclinical studies that DOACs exhibit also non-anticoagulant actions, such as anti-inflammatory and anti-oxidant actions, advocating overall cardiovascular protection. In the present study, we provide a comprehensive overview of the existing knowledge on the pleiotropic effects of DOACs on endothelial cells (ECs) in vitro and their underlying mechanisms, while also identifying potential differences among DOACs. DOACs exhibit pleiotropic actions on ECs, such as anti-inflammatory, anti-atherosclerotic, and anti-fibrotic effects, as well as preservation of endothelial integrity. These effects appear to be mediated through inhibition of the proteinase-activated receptor signaling pathway. Furthermore, we discuss the potential differences among the four drugs in this class. Further research is needed to fully understand the pleiotropic effects of DOACs on ECs, their underlying mechanisms, as well as the heterogeneity between various DOACs. Such studies can pave the way for identifying biomarkers that can help personalize pharmacotherapy with this valuable class of drugs.

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Dabigatran attenuates methotrexate-induced hepatotoxicity by regulating coagulation, endothelial dysfunction, and the NF-kB/IL-1β/MCP-1 and TLR4/NLRP3 signaling pathways

El-Dessouki,

Alzokaky,

Raslan

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

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Dabigatran: its protective effect against endothelial cell damage by oxysterol

Cited by 6 publications

References 26 publications

SGLT2 Inhibitors May Restore Endothelial Barrier Interrupted by 25-Hydroxycholesterol

SGLT2 Inhibitors May Restore Endothelial Barrier Interrupted by 25-Hydroxycholesterol

Distinct pleiotropic effects of direct oral anticoagulants on cultured endothelial cells: a comprehensive review

Dabigatran attenuates methotrexate-induced hepatotoxicity by regulating coagulation, endothelial dysfunction, and the NF-kB/IL-1β/MCP-1 and TLR4/NLRP3 signaling pathways

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