COUP-TFII is Regulated by High Glucose in Endothelial Cells

Brunßen, Coy; Korten, Slobodanka; Brux, Melanie; Seifert, Scott A.; Roesler, J M; Bornstein, Stefan R.; Morawietz, Henning; Göettsch, Winfried

doi:10.1055/s-0029-1241862

Cited by 10 publications

(7 citation statements)

References 27 publications

(32 reference statements)

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“…Primary cultures of HUVEC were isolated using 0.5% collagenase II solution (Worthington Biochemical Corp., Lakewood NJ, USA) [32], [33], [34]. Isolated HUVEC were cultured on 2% gelatin-coated plates in Medium 199 (Thermo Fisher Scientific, Waltham, MA, USA), supplemented with 10% fetal calf serum (Biochrom, Berlin, Germany), 0.5% self-isolated retina calf eye growth supplement [35], 100,000 U/l penicillin (Thermo Fisher Scientific, Waltham, MA, USA), 100 mg/l streptomycin (Thermo Fisher Scientific, Waltham, MA, USA) and 250 mg/l Fungizone (Thermo Fisher Scientific, Waltham, MA, USA). HUVEC were freshly isolated on a weekly manner and only used for experiments up to passage 2.…”

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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“…Surgery and transplantation are also associated with hypoxia, which is kept as short as possible. The choice of the period of the short-term hypoxia was based on studies already conducted by other groups, such as Brunssen et al (short-term hypoxia 60-240 min) and Wein et al (short-term hypoxia 30-60 min) [68,69].…”

Section: Hypoxia and Normoxia Conditionsmentioning

confidence: 99%

Impact of Short-Term Hypoxia on Sirtuins as Regulatory Elements in HUVECs

Pecher

Potthast

Versen‐Höynck

2020

JCM

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Background: Sirtuins (SIRT) are NAD+-dependent deacetylases that are involved in stress response, antioxidative defense, and longevity via posttranslational modifications. SIRT1 directly activates nitric oxide synthase (NOS). Aging is associated with a reduced sirtuin function and reduction of the cofactor NAD+. Age-related atherosclerosis and vascular diseases are linked to a compromised sirtuin function. Vascular events like stroke and cardiac infarction result in acute hypoxia, which can additionally impact sirtuins and thus the vascular function. This prompted us to study sirtuins in intact HUVECs, under acute, short-term hypoxic conditions. Methods: We measured intracellular sirtuin and NAD+ levels in HUVECs exposed to hypoxia (2% O₂) for 10–120 min, compared to normoxic controls. SIRT1, SIRT3, and SIRT4 were measured at the protein (Western Blot) and the transcript level (qRT-PCR), SIRT1 and SIRT3 at the enzyme level (fluorometrically), and NAD+ levels were measured spectrophotometrically. Results: We observed a reduction of SIRT1 and SIRT4 at the protein level, a downregulation of SIRT1 at the transcript level and increased NAD+ levels under hypoxia. SIRT3 was not affected by hypoxia. Conclusions: Downregulation of SIRT1 under hypoxia might reduce production of the reactive oxygen species (ROS) via the respiratory chain and inhibit the mitochondrial ATP-synthase, resulting in energy conservation. NOS might be impaired if SIRT1 is decreased. Increased NAD+ levels might compensate these effects. Hypoxic downregulation of SIRT4 might lead to mitochondrial uncoupling, hence endothelial dysfunction, and ADP/ATP-translocase 2 (ANT2)-inhibition. NAD+ upregulation might partly compensate this effect.

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“…Rao et al investigated the association between glucose levels and ankle range of motion and stiffness and found that passive ankle stiffness and reduced dorsiflexion range of motion were increased in individuals with DM [20]. Research has also revealed that elevated glucose may increase oxidative stress, which induces endothelial dysfunction and impairs venoconstriction responsiveness [21,22], and that hypertriglyceridaemia could exacerbate endothelial inflammation and induce endothelial dysfunction [23,24]. These factors may explain why DM is the most important risk factor, among all the components of MS, for early CVD in our study and why the blood glucose and TG control status is associated with venous function of the lower extremities in diabetic patients.…”

Section: Discussionmentioning

confidence: 99%