Effect of High Glucose Concentrations on Expression of ELAM 1, VCAM-1 and ICAM-1 in HUVEC with and without Cytokine Activation.

Altannavch, Tsevegjav; Roubalová, K; Kučera, Petr; Andĕl, M

doi:10.33549/physiolres.930343

Cited by 88 publications

(7 citation statements)

References 30 publications

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“…Besides the role of CTSS in inflammatory cytokine regulation, this study determined the effect of CTSS silencing on adhesion molecules such as VCAM-1 and ICAM-1. Similar to other studies, our study showed that hyperglycemia increased the expression of VCAM-1, ICAM-1, and VEGF-1 in HUVEC cells [ 29 , 47 ]. Hyperglycemia has been shown to increase the permeability of HUVEC monolayers, which is an early pathological mechanism in the progression of diabetic vascular complications [ 48 ].…”

Section: Discussionsupporting

confidence: 91%

Cathepsin S Knockdown Suppresses Endothelial Inflammation, Angiogenesis, and Complement Protein Activity under Hyperglycemic Conditions In Vitro by Inhibiting NF-κB Signaling

Sayed

Faruq

Preya

et al. 2023

IJMS

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Hyperglycemia plays a key role in the development of microvascular complications, endothelial dysfunction (ED), and inflammation. It has been demonstrated that cathepsin S (CTSS) is activated in hyperglycemia and is involved in inducing the release of inflammatory cytokines. We hypothesized that blocking CTSS might alleviate the inflammatory responses and reduce the microvascular complications and angiogenesis in hyperglycemic conditions. In this study, we treated human umbilical vein endothelial cells (HUVECs) with high glucose (HG; 30 mM) to induce hyperglycemia and measured the expression of inflammatory cytokines. When treated with glucose, hyperosmolarity could be linked to cathepsin S expression; however, many have mentioned the high expression of CTSS. Thus, we made an effort to concentrate on the immunomodulatory role of the CTSS knockdown in high glucose conditions. We validated that the HG treatment upregulated the expression of inflammatory cytokines and CTSS in HUVEC. Further, siRNA treatment significantly downregulated CTSS expression along with inflammatory marker levels by inhibiting the nuclear factor-kappa B (NF-κB) mediated signaling pathway. In addition, CTSS silencing led to the decreased expression of vascular endothelial markers and downregulated angiogenic activity in HUVECs, which was confirmed by a tube formation experiment. Concurrently, siRNA treatment reduced the activation of complement proteins C3a and C5a in HUVECs under hyperglycemic conditions. These findings show that CTSS silencing significantly reduces hyperglycemia-induced vascular inflammation. Hence, CTSS may be a novel target for preventing diabetes-induced microvascular complications.

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Section: Discussionsupporting

confidence: 91%

Cathepsin S Knockdown Suppresses Endothelial Inflammation, Angiogenesis, and Complement Protein Activity under Hyperglycemic Conditions In Vitro by Inhibiting NF-κB Signaling

Sayed

Faruq

Preya

et al. 2023

IJMS

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“…3 However, the direct influence, if any, of hyperglycemia on atherogenesis remains unclear. Increased expression of vascular cellular adhesion molecules in the diabetic endothelial cell has been shown in in vitro 4 and in vivo studies. 5 Furthermore, short-term hyperglycemia promotes monocyte adhesion to rat thoracic aorta 6 and to human aortic endothelial cells.…”

mentioning

confidence: 86%

Effect of Hyperglycemia on Human Monocyte Activation

Nandy

Janardhanan

Mukhopadhyay

et al. 2011

Journal of Investigative Medicine

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Our recent study defined the chemokine induced human monocyte signaling under normoglycemic condition. To explore the hyperglycemia induced monocyte signaling, we performed adhesion, migration and transmigration assays on human monocytes obtained from THP-1 cell line in the presence of normal (5mM) and high (10 and 20mM) glucose concentrations without chemokines. We observed augmented (p<0.01) monocyte adhesion to HUVEC monolayer at 10mM than 5mM glucose with no further increase at 20mM glucose concentration (p<0.03 vs. 10mM; p<0.01 vs. 5mM). But incremental increase in monocyte migration (p<0.01), transmigration (p<0.01) and stress fibre response (p<0.01) were observed at 10 and 20mM glucose concentrations in comparison to 5mM glucose concentrations. We found gradational increase (p<0.01) in phosphorylation of Akt S473 and glycogen synthase kinase (GSK3β S9) in hyperglycemia (10 and 20mM) when compared to 5mM glucose. Furthermore hyperglycemia (both 10 mM and 20 mM) treated monocyte showed upregulated phosphorylation of p101 and p110γ subunits of PI-3 kinase in comparison to 5mM glucose. Hyperglycemia induced monocyte migration was restored to basal levels in the presence of PI-3 kinase inhibitor, LY. These observations imply that modest hyperglycemia per se, as is commonly observed in diabetic individuals, is a potent stimulator of monocyte activity even without chemokines.

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“…In HUVEC, however, high glucose culture did not show any increase in inflammation. This comes in contrast to previously reported findings in HUVEC showing significant increases in the inflammatory surface markers, ICAM1, VCAM1 and endothelialleukocyte adhesion molecular 1 (ELAM1) upon exposure to higher glucose concentrations, peaking at 16.5 mM [346][347]. Interestingly, in the study by Altannavch et [346].…”

Section: High Glucose Culture To Model Dmcontrasting

confidence: 86%

Cardiac microvascular dysfunction in diabetes mellitus: elucidation of molecular determinants and therapeutic targets

Samak¹

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gezeigt, dass die Hemmung von miR-92a die Werte dieser Targets in diabetischen HCMEC wiederherstellt. Insgesamt zeigen meine Ergebnisse neue molekulare Mechanismen in derPathogenese der kardialen mikrovaskulären Dysfunktion bei Diabetes mellitus auf und qualifizieren miR-92a nachdrücklich als therapeutisches Ziel. Type 1 diabetes mellitus (T1DM)Type 1 DM is a chronic autoimmune disease characterized by progressive destruction of the pancreatic insulin producing beta cells (β-cells) in the islets of Langerhans by cytotoxic T-cells, resulting in insulin deficiency and hyperglycemia [10]. T1DM is a polygenic disease, wherein various susceptibility genes, along with precipitating environmental and/or infectious agents trigger an overt immune reaction to β-cells [11]. As a result, the endocrine pancreas is infiltrated with cytotoxic CD8+ T-cells along with cells of the innate immune system, as well as B-lymphocytes [10][11]. The latter release autoantibodies against β-cell proteins, which are characteristic measures in the blood of T1DM patients [10]. The disease usually presents itself in children or young individuals, hence previously known as juvenile-onset DM. This can be misleading, since T1DM can occur in any age, with 50% of cases occurring in adults, of which half are misdiagnosed as type 2 DM [12][13]. T1DM affects one in every 250 individuals on average, with more male than female bias [14]. The incidence of T1DM has been on the rise, with overall annual increase of 2 -3%, mostly children under 15 years old, peaking at those < 5 years old [15]. Type 1 diabetic patients are strictly dependent on exogenous insulin with high risk of life-threatening bouts of hypoglycemia, and on the other end, diabetic ketoacidosis [10].These critical conditions have been associated with neurocognitive complications in type 1 diabetic patients, which are linked to diabetes-induced vascular disease [16][17][18]. Type 1 diabetics succumb to the notorious long-term complications of DM, including retinopathy, nephropathy and neuropathy, and above all cardiovascular disease (CVD) (discussed below) [19][20][21][22]. Despite recent improvements in management, T1DM continues to be associated with increased total mortality. In young adults with T1DM, i.e. <45 years old, total mortality is 5 fold higher than among age-matched non-diabetics [23]. pancreatic compensation fails in face of insulin resistance, leading to β-cell dysfunction [26][27]. The triad of increased blood glucose, insulin and free fatty acids is an ominous metabolic state that evoke a number of deleterious cascades, such as glucotoxicity, lipotoxicity, oxidative stress, dyslipidemia and inflammation, that inflict all organ systems [28][29]. These manifest in a wide range of diabetic infamous complications, such as retinopathy, neuropathy, nephropathy and above all, CVD (discussed below) [26]. Importantly, T2DM harbors a genetic component that has recently become appreciated thanks to advancing genome wide association studies (GWAS). Over 500 risk variants and susceptibi...

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Effect of High Glucose Concentrations on Expression of ELAM 1, VCAM-1 and ICAM-1 in HUVEC with and without Cytokine Activation.

Cited by 88 publications

References 30 publications

Cathepsin S Knockdown Suppresses Endothelial Inflammation, Angiogenesis, and Complement Protein Activity under Hyperglycemic Conditions In Vitro by Inhibiting NF-κB Signaling

Cathepsin S Knockdown Suppresses Endothelial Inflammation, Angiogenesis, and Complement Protein Activity under Hyperglycemic Conditions In Vitro by Inhibiting NF-κB Signaling

Effect of Hyperglycemia on Human Monocyte Activation

Cardiac microvascular dysfunction in diabetes mellitus: elucidation of molecular determinants and therapeutic targets

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