Serelaxin (recombinant human relaxin-2) prevents high glucose-induced endothelial dysfunction by ameliorating prostacyclin production in the mouse aorta

AbstractEndothelial dysfunction is closely associated with diabetic complications. Icariin, a flavonoid glycoside isolated from the Epimedium plant species, exhibits antidiabetic properties. However, its impact on endothelial function remains poorly understood, particularly under hyperglycemia. In this study, we investigated the potential protective effect of icariin on high glucose-induced detrimental effects on vascular endothelial cells. Human umbilical venous endothelial cells were incubated in media containing 5.5 mM glucose (normal glucose) or 25 mM glucose (high glucose) in the presence or absence of 50 µM icariin for 72 h. We found that high glucose markedly induced cell apoptosis, enhanced reactive oxygen species generation, and elevated expression levels of inflammatory factors and cell adhesion molecules, which were greatly subdued by icariin supplementation. In conclusion, icariin exerted a beneficial effect on high glucose-induced endothelial dysfunction. This new finding provides a promising strategy for future treatment of diabetic vascular complications.

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Low nanomolar caffeic acid attenuates high glucose-induced endothelial dysfunction in primary human umbilical-vein endothelial cells by affecting NF-κB and Nrf2 pathways

BioFactors ◽

10.1002/biof.1312 ◽

2016 ◽

Vol 43 (1) ◽

pp. 54-62 ◽

Cited By ~ 21

Author(s):

Deborah Fratantonio ◽

Antonio Speciale ◽

Raffaella Canali ◽

Lucia Natarelli ◽

Daniela Ferrari ◽

...

Keyword(s):

Endothelial Cells ◽

Endothelial Dysfunction ◽

Caffeic Acid ◽

High Glucose ◽

Umbilical Vein ◽

Human Umbilical Vein ◽

Umbilical Vein Endothelial Cells

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CTRP3 Protects against High Glucose-Induced Cell Injury in Human Umbilical Vein Endothelial Cells

Analytical Cellular Pathology ◽

10.1155/2019/7405602 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Fang Wang ◽

Linlin Zhao ◽

Yingguang Shan ◽

Ran Li ◽

Guijun Qin

Keyword(s):

Endothelial Cells ◽

Endothelial Dysfunction ◽

High Glucose ◽

Cell Injury ◽

Umbilical Vein ◽

Cell Loss ◽

Inflammatory Factors ◽

Therapeutic Drug ◽

Human Umbilical Vein ◽

Umbilical Vein Endothelial Cells

Aims. Inflammation was closely associated with diabetes-related endothelial dysfunction. C1q/tumor necrosis factor-related protein 3 (CTRP3) is a member of the CTRP family and can provide cardioprotection in many cardiovascular diseases via suppressing the production of inflammatory factors. However, the role of CTRP3 in high glucose- (HG-) related endothelial dysfunction remains unclear. This study evaluates the effects of CTRP3 on HG-induced cell inflammation and apoptosis. Materials and Methods. To prevent high glucose-induced cell injury, human umbilical vein endothelial cells (HUVECs) were pretreated with recombinant CTRP3 for 1 hour followed by normal glucose (5.5 mmol/l) or high glucose (33 mmol/l) treatment. After that, cell apoptosis and inflammatory factors were determined. Results. Our results demonstrated that CTRP3 mRNA and protein expression were significantly decreased after HG exposure in HUVECs. Recombinant human CTRP3 inhibited HG-induced accumulation of inflammatory factors and cell loss in HUVECs. CTRP3 treatment also increased the phosphorylation levels of protein kinase B (AKT/PKB) and the mammalian target of rapamycin (mTOR) in HUVECs. CTRP3 lost its inhibitory effects on HG-induced cell inflammation and apoptosis after AKT inhibition. Knockdown of endogenous CTRP3 in HUVECs resulted in increased inflammation and decreased cell viability in vitro. Conclusions. Taken together, these findings indicated that CTRP3 treatment blocked the accumulation of inflammatory factors and cell loss in HUVECs after HG exposure through the activation of AKT-mTOR signaling pathway. Thus, CTRP3 may be a potential therapeutic drug for the prevention of diabetes-related endothelial dysfunction.

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Myeloperoxidase amplified high glucose-induced endothelial dysfunction in vasculature: Role of NADPH oxidase and hypochlorous acid

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2017.01.132 ◽

2017 ◽

Vol 484 (3) ◽

pp. 572-578 ◽

Cited By ~ 25

Author(s):

Rong Tian ◽

Yun Ding ◽

Yi-Yuan Peng ◽

Naihao Lu

Keyword(s):

Endothelial Dysfunction ◽

Nadph Oxidase ◽

High Glucose ◽

Hypochlorous Acid

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Mechanisms Mediating the Protective Effect of Curcumin on Vascular Endothelial Dysfunction Induced by High Glucose

Journal of Physiology and Pharmacology Advances ◽

10.5455/jppa.20130320024131 ◽

2013 ◽

Vol 3 (3) ◽

pp. 85 ◽

Cited By ~ 1

Author(s):

Rama Mangipudi ◽

Chris Hillier

Keyword(s):

Endothelial Dysfunction ◽

Protective Effect ◽

High Glucose ◽

Vascular Endothelial ◽

Vascular Endothelial Dysfunction

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Ellagic Acid Reduces High Glucose-Induced Vascular Oxidative Stress Through ERK1/2/NOX4 Signaling Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000485448 ◽

2017 ◽

Vol 44 (3) ◽

pp. 1174-1187 ◽

Cited By ~ 24

Author(s):

Artur Rozentsvit ◽

Kevin Vinokur ◽

Sherin Samuel ◽

Ying Li ◽

A. Martin Gerdes ◽

...

Keyword(s):

Oxidative Stress ◽

Endothelial Dysfunction ◽

Protective Effect ◽

High Glucose ◽

Ellagic Acid ◽

Biological Activities ◽

Radical Scavenging ◽

Vascular Complications ◽

Ros Production ◽

Gene And Protein Expression

Background/Aims: Elevated production of reactive oxygen species (ROS) is linked to endothelial dysfunction and is one of the key contributors to the pathogenesis of diabetic vascular complications. Emerging evidence has indicated that ellagic acid (EA), a polyphenol found in fruits and nuts, possesses numerous biological activities including radical scavenging. However, whether EA exerts a vasculo-protective effect via antioxidant mechanisms in blood vessels exposed to diabetic conditions remains unknown. Accordingly, the goal of this current study was to determine whether EA decreases vascular ROS production and thus ameliorates endothelial dysfunction in the diabetic milieu. Methods: Intact rat aortas and human aortic endothelial cells (HAEC) were stimulated with 30mM high glucose (HG) with and without EA co-treatment. Endothelium-dependent vasodilation was measured using a wire myograph. Gene and protein expression of non-phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidases 4 (NOX4) were detected using RT-PCR and western blotting, respectively. Oxidative stress was determined by measuring ROS levels using dihydroethidium (DHE) staining. Results: Intact aortas exposed to HG condition displayed exacerbated ROS production and impairment of endothelium-dependent vasodilation, characterizing endothelial dysfunction. These effects were markedly reduced with EA treatment. HG enhanced ROS production in HAEC, paralleled by increased ERK1/2 activation and NOX4 expression. EA treatment blunted the increase of ROS generation, ERK1/2 activation and decreased NOX4. Conclusions: EA significantly decreases endothelial ROS levels and ameliorates the impairment of vascular relaxation induced by HG. Our results suggest that EA exerts a vasculo-protective effect under diabetic conditions via an antioxidant effect that involves inhibition of ERK1/2 and downregulation of NOX4.

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