Role of Endothelial Dysfunction and Endocan in Atherosclerosis: Point of Origin or End Point?

Canpolat, Uğur; Koçyiğit, Duygu; Yıldırım, Arzu

doi:10.1177/0003319716654627

Cited by 18 publications

(16 citation statements)

References 12 publications

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“…In patients with cardiac ischemia, circulating EMPs correlate positively with the disease severity and inversely with endothelial function assessed by FMD [86]. Endoglin or CD105 [87][88][89], a receptor for transforming growth factor beta (TGF-β), and Endocan, a soluble proteoglycan secreted by vascular endothelial cells [90], are additional putative biomarkers of ED. Among all biomarkers of ED, ADMA is perhaps the most accepted marker of ED.…”

Section: Biomarkers Of Endothelial Biologymentioning

confidence: 99%

Endothelial Dysfunction in Chronic Kidney Disease, from Biology to Clinical Outcomes: A 2020 Update

Roumeliotis

Mallamaci

Zoccali

2020

JCM

175

128

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The vascular endothelium is a dynamic, functionally complex organ, modulating multiple biological processes, including vascular tone and permeability, inflammatory responses, thrombosis, and angiogenesis. Endothelial dysfunction is a threat to the integrity of the vascular system, and it is pivotal in the pathogenesis of atherosclerosis and cardiovascular disease. Reduced nitric oxide (NO) bioavailability is a hallmark of chronic kidney disease (CKD), with this disturbance being almost universal in patients who reach the most advanced phase of CKD, end-stage kidney disease (ESKD). Low NO bioavailability in CKD depends on several mechanisms affecting the expression and the activity of endothelial NO synthase (eNOS). Accumulation of endogenous inhibitors of eNOS, inflammation and oxidative stress, advanced glycosylation products (AGEs), bone mineral balance disorders encompassing hyperphosphatemia, high levels of the phosphaturic hormone fibroblast growth factor 23 (FGF23), and low levels of the active form of vitamin D (1,25 vitamin D) and the anti-ageing vasculoprotective factor Klotho all impinge upon NO bioavailability and are critical to endothelial dysfunction in CKD. Wide-ranging multivariate interventions are needed to counter endothelial dysfunction in CKD, an alteration triggering arterial disease and cardiovascular complications in this high-risk population.

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Section: Biomarkers Of Endothelial Biologymentioning

confidence: 99%

Endothelial Dysfunction in Chronic Kidney Disease, from Biology to Clinical Outcomes: A 2020 Update

Roumeliotis

Mallamaci

Zoccali

2020

JCM

175

128

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“…Endothelial cell-to-cell junctions play a major role in the early stages of atherosclerosis, which are associated with inflammation and endothelial dysfunction456. The vascular endothelium is a layer of cells that lines the blood vessels and serves as the primary barrier between blood and tissues.…”

mentioning

confidence: 99%

TNF-α regulates the proteolytic degradation of ST6Gal-1 and endothelial cell-cell junctions through upregulating expression of BACE1

Deng

Zhang

Liu

et al. 2017

Sci Rep

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Endothelial dysfunction and monocyte adhesion to vascular endothelial cells are two critical steps in atherosclerosis development, and emerging evidence suggests that protein sialylation is involved in these processes. However, the mechanism underlying this phenomenon remains incompletely elucidated. In this study, we demonstrated that treatment with the proinflammatory cytokine TNF-α disrupted vascular endothelial cell-cell tight junctions and promoted monocyte endothelial cell adhesion. Western blotting and Sambucus nigra lectin (SNA) blotting analyses revealed that TNF-α treatment decreased α-2, 6-sialic acid transferase 1 (ST6Gal-I) levels and downregulated VE-Cadherin α-2, 6 sialylation. Further analysis demonstrated that TNF-α treatment upregulated β-site amyloid precursor protein enzyme 1 (BACE1) expression, thus resulting in sequential ST6Gal-I proteolytic degradation. Furthermore, our results revealed that PKC signaling cascades were involved in TNF-α-induced BACE1 upregulation. Together, these results indicated that the proinflammatory cytokine TNF-α impairs endothelial tight junctions and promotes monocyte-endothelial cell adhesion by upregulating BACE1 expression through activating PKC signaling and sequentially cleaving ST6Gal-I. Thus, inhibition of BACE1 expression may be a new approach for treating atherosclerosis.

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“…Endocan-1 levels, on the other hand, are markedly increased in highly inflammatory states such as sepsis and hypervascular states such as cardiovascular disease and certain cancer states (224)(225)(226)(227)(228). It has been hypothesised that increased levels might be a protective response, as endocan-1 is vasoprotective in normal physiological conditions (229). Low levels might therefore be indicative of insufficient vasoprotective capability, thereby explaining decreased concentrations in chronic low inflammatory conditions.…”

Section: Departments Of Dermatology At Linköping University Hospitalmentioning

confidence: 99%

Studies of the Systemic Inflammation in Psoriasis

Sigurdardottir¹

2018

Linköping University Medical Dissertations

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Front cover and illustration by Gunnþórunn Sigurðardóttir with graphic assistance from LiU-Tryck, Linköping.Psoriasis is a common immune-mediated disease, where an increased prevalence of extra cutaneous diseases and mortality is observed. Common inflammatory mechanisms are implicated. The general aim of this thesis was to investigate markers of inflammation and cardiovascular disease in psoriasis, now considered a systemic disease, assumed to reflect the systemic inflammation.In Study I, Th1-, Th2-and Th17-associated chemokines were elevated in the blood of psoriasis patients in comparison to controls and, in Study II, six markers of cardiovascular risk were demonstrated to be systemically elevated. After adjustment for body mass index and waist: hip ratio in Study II, only one marker, the total plasminogen activator inhibitor-1, showed sustained elevated levels. The levels of the chemokines and the cardiovascular markers were unaffected after treatment with narrowband UVB therapy (NB-UVB), despite a significant improvement in skin lesions, indicating more local than systemic effects of NB-UVB. This was further strengthened by the fact that the response to in-vitro stimulation in the peripheral blood mononuclear cells (PBMCs) of psoriasis patients before and after NB-UVB treatment was unaffected. In Study I, CCL20 was shown to correlate to the psoriasis area severity index (PASI), but this correlation was lost after phototherapy, suggesting sources of CCL20 other than the skin. Conversely, systemic treatment with TNF-α inhibition in Study II alleviated the elevated systemic levels of the cardiovascular risk markers. In Study III, the levels of 17 potential biomarkers, with the emphasis on endothelial and adipocyte dysfunction, soluble receptors and the innate mechanisms were studied. Endocan-1, CXCL16, and sVEGFR1, were found to be systemically decreased in psoriasis patients at baseline. Endocan-1 showed a negative correlation to the PASI. In contrast to the results in Studies I and II, NB-UVB therapy affected the systemic levels of investigated markers; Endocan-1 and CXCL16 were restored to normal levels, while sVEGF1, FABP3, FABP4 and sIL-1R1 showed a significant reduction following NB-UVB. In Study IV, the focus was on the contribution of innate immune mechanisms and the effects of the cytokines IL-17 and TNF-α on systemic inflammation. In keratinocytes, the gene and protein expression of inflammasome components was increased upon exposure to IL-17 and TNF-α. Systemically, the constitutive expression of the inflammasome components NLRP1, NLRP3 and AIM2 was detected in neutrophils, classical monocytes, CD4+ lymphocytes and B-cell subsets from psoriasis patients. Upon exposure to IL-17 and TNF-α, increased systemic caspase-1 levels were detected, confirming systemic inflammasome activity.In conclusion, these studies support the hypothesis that there is a systemic inflammation in psoriasis to which both innate and adaptive immune mechanisms contribute. The systemic inflammation may be explained, to some extent,...

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Role of Endothelial Dysfunction and Endocan in Atherosclerosis: Point of Origin or End Point?

Cited by 18 publications

References 12 publications

Endothelial Dysfunction in Chronic Kidney Disease, from Biology to Clinical Outcomes: A 2020 Update

Endothelial Dysfunction in Chronic Kidney Disease, from Biology to Clinical Outcomes: A 2020 Update

TNF-α regulates the proteolytic degradation of ST6Gal-1 and endothelial cell-cell junctions through upregulating expression of BACE1

Studies of the Systemic Inflammation in Psoriasis

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