The relationship between early atherosclerosis and endothelial dysfunction in type 1 diabetic patients as evidenced by measurement of carotid intima-media thickness and soluble CD146 levels: a cross sectional study

Dogansen, Sema Ciftci; Helvacı, Ayşen; Adaş, Mine; Onal, Suzan Deniz

doi:10.1186/1475-2840-12-153

Cited by 18 publications

(11 citation statements)

References 38 publications

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“…An abnormal elevation in serum sCD146 has been reported to be correlated with the activity of ECs. In early diabetes and diabetic nephropathy, serum sCD146 is significantly increased and positively correlated with the pathological process of disease, suggesting vascular system dysfunction 20, 55. In addition, serum sCD146 is also abnormally elevated in acutely decompensated heart failure, acute coronary syndrome and other cardiovascular diseases, indicating damage to ECs 53, 56.…”

Section: Discussionmentioning

confidence: 99%

Soluble CD146, a cerebrospinal fluid marker for neuroinflammation, promotes blood-brain barrier dysfunction

Wang¹,

Duan²,

Feng³

et al. 2020

Theranostics

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The blood-brain barrier (BBB) dysfunction is an initial event of various neuroinflammatory diseases. However, the absence of reliable markers and mechanisms for BBB damage greatly limits the diagnosis and treatment of neuroinflammatory diseases. Soluble CD146 (sCD146) is mainly derived from vascular endothelial cells (ECs) and highly elevated in inflammatory settings. Based on a small cohort, our previous study showed that sCD146 is elevated in the cerebrospinal fluid (CSF) of multiple sclerosis (MS), which is accompanied with BBB damage. Nevertheless, whether sCD146 monitors and regulates the BBB dysfunction remains unknown.Methods: Coupled serum and CSF samples from patients with or without neuroinflammatory diseases were collected via multicenter collaborations. sCD146 was measured by sandwich ELISA using anti-CD146 antibodies AA1 and AA98, both of which were generated in our laboratory. The correlations between sCD146 and other clinical parameters or inflammatory factors were analyzed by Spearman's correlation coefficient analysis. The role of sCD146 on BBB function was examined in an in vitro BBB model.Results: Between July 20, 2011, and February 31, 2017, we collected coupled serum and CSF samples from 823 patients, of which 562 (68.3%) had neuroinflammatory diseases, 44 (5.3%) had remitting MS, and 217 (26.4%) had non-inflammatory neurological diseases (NIND). We found that sCD146 in CSF, but not in serum, is abnormally elevated in neuroinflammatory diseases (37.3 ± 13.3 ng/mL) compared with NIND (4.7 ± 2.9 ng/mL) and remitting MS (4.6 ± 3.5 ng/mL). Abnormally elevated CSF sCD146 is significantly correlated with the hyperpermeability-related clinical parameters of BBB and neuroinflammation-related factors. Moreover, CSF sCD146 shows higher sensitivity and specificity for evaluating BBB damage. Using an in vitro BBB model, we found that sCD146 impairs BBB function by promoting BBB permeability via an association with integrin αvβ1. Blocking integrin αvβ1 significantly attenuates sCD146-induced hyperpermeability of the BBB.Conclusion: Our study provides convincing evidence that CSF sCD146 is a sensitive marker of BBB damage and neuroinflammation. Furthermore, sCD146 is actively involved in BBB dysfunction.

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Section: Discussionmentioning

confidence: 99%

Soluble CD146, a cerebrospinal fluid marker for neuroinflammation, promotes blood-brain barrier dysfunction

Wang¹,

Duan²,

Feng³

et al. 2020

Theranostics

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“…A recent report shows increased concentrations of MCAM 3 months after CABG [ 27 ]. Some researchers have confirmed a role of MCAM as an endothelial cell dysfunction marker in diabetic patients [ 28 , 29 ]. Thus, MCAM is considered a candidate gene involved in ED.…”

Section: Discussionmentioning

confidence: 99%

Long Noncoding RNA uc001pwg.1 Is Downregulated in Neointima in Arteriovenous Fistulas and Mediates the Function of Endothelial Cells Derived from Pluripotent Stem Cells

Guo

et al. 2017

Stem Cells International

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Recent studies indicate important roles for long noncoding RNAs (lncRNAs) as essential regulators of gene expression. However, the specific roles of lncRNAs in stenotic lesions of arteriovenous fistula (AVF) failure are still largely unknown. We first analyzed the expression profiles of lncRNAs in human stenosed and nonstenotic uremic veins using RNA-sequencing methodology. A total of 19 lncRNAs were found to be differentially expressed in stenotic lesions. Among these, uc001pwg.1 was one of the most significantly downregulated lncRNAs and enriched in both control vein segments and human umbilical vein endothelial cells (HUVECs). Further studies revealed that uc001pwg.1 overexpression could increase nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) production in endothelial cells (ECs) derived from human-induced pluripotent stem cells (HiPSCs). Mechanistically, uc001pwg.1 improves endothelial function via mediating MCAM expression. This study represents the first effort of identifying a novel candidate lncRNA for modulating the function of iPSC-ECs, which may facilitate the improvement of stem cell-based therapies for AVF failure.

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“…Ultrastructural analysis of aorta was focused on vascular endothelial cells, because the senescent endothelial cells may critically disturb the integrity of the endothelial monolayer and may thereby contribute to vascular injury and atherosclerosis [15][16][17][18][19].The endothelial cell in control group showed a fusiform, smooth shape and even chromatin ( Fig. 1A).…”

Section: Ultrastructural Degeneration Of Aorta With Ageing and The Efmentioning

confidence: 99%

Valsartan ameliorates ageing‐induced aorta degeneration via angiotensin II type 1 receptor‐mediated ERK activity

Huang

Zhang

et al. 2014

J Cellular Molecular Medi

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Angiotensin II (Ang II) plays important roles in ageing-related disorders through its type 1 receptor (AT1R). However, the role and underlying mechanisms of AT1R in ageing-related vascular degeneration are not well understood. In this study, 40 ageing rats were randomly divided into two groups: ageing group which received no treatment (ageing control), and valsartan group which took valsartan (selective AT1R blocker) daily for 6 months. 20 young rats were used as adult control. The aorta structure were analysed by histological staining and electron microscopy. Bcl-2/Bax expression in aorta was analysed by immunohistochemical staining, RT-PCR and Western blotting. The expressions of AT1R, AT2R and mitogen-activated protein kinases (MAPKs) were detected. Significant structural degeneration of aorta in the ageing rats was observed, and the degeneration was remarkably ameliorated by long-term administration of valsartan. With ageing, the expression of AT1R was elevated, the ratio of Bcl-2/Bax was decreased and meanwhile, an important subgroup of MAPKs, extracellular signal-regulated kinase (ERK) activity was elevated. However, these changes in ageing rats could be reversed to some extent by valsartan. In vitro experiments observed consistent results as in vivo study. Furthermore, ERK inhibitor could also acquire partial effects as valsartan without affecting AT1R expression. The results indicated that AT1R involved in the ageing-related degeneration of aorta and AT1R-mediated ERK activity was an important mechanism underlying the process.

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The relationship between early atherosclerosis and endothelial dysfunction in type 1 diabetic patients as evidenced by measurement of carotid intima-media thickness and soluble CD146 levels: a cross sectional study

Cited by 18 publications

References 38 publications

Soluble CD146, a cerebrospinal fluid marker for neuroinflammation, promotes blood-brain barrier dysfunction

Soluble CD146, a cerebrospinal fluid marker for neuroinflammation, promotes blood-brain barrier dysfunction

Long Noncoding RNA uc001pwg.1 Is Downregulated in Neointima in Arteriovenous Fistulas and Mediates the Function of Endothelial Cells Derived from Pluripotent Stem Cells

Valsartan ameliorates ageing‐induced aorta degeneration via angiotensin II type 1 receptor‐mediated ERK activity

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