The role of adipocytokines and endothelial dysfunction with irritable bowel syndrome associated with obesity

The article contains the analysis of results concerning investigation of adipocytokines content and endothelial dysfunction in 97 patients with irritable bowel syndrome associated with obesity. The blood serum was examined for the content of adipocytokines (leptin, adiponectin, resistin), stable nitrogen monoxide metabolites (nitrites/nitrates), endothelin-1, intercellular adhesion molecule 1 (ICAM-1), and the number of circulating endothelial cells (CEC). Patients with IBS associated with obesity and prevailing diarrhea are found to develop a prominent imbalance of adipocytokines which is manifested in high levels of leptin and resisin and low level of adiponectin in the blood serum. Endothelial dysfunction evidenced by a high level of endothelin-1, the number of circulating endothelial cells, general NO and intercellular adhesion molecules 1, is characteristic for patients with IBS associated with obesity and prevailing diarrhea.

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dsRNA activation of endothelin-1 and markers of vascular activation in endothelial cells and fibroblasts

Annals of the Rheumatic Diseases ◽

10.1136/ard.2010.132464 ◽

2010 ◽

Vol 70 (3) ◽

pp. 544-550 ◽

Cited By ~ 27

Author(s):

Giuseppina Farina ◽

Michael York ◽

Cindy Collins ◽

Robert Lafyatis

Keyword(s):

Endothelial Cells ◽

Adhesion Molecule ◽

Intercellular Adhesion ◽

Dermal Fibroblasts ◽

Innate Immune ◽

Poly I:C ◽

Intercellular Adhesion Molecule ◽

Type I ◽

Intercellular Adhesion Molecule 1 ◽

Endothelin 1

BackgroundIn patients with systemic sclerosis (SSc), the relationship between innate immune activation, represented by increased expression of interferon (IFN)-regulated genes, and vascular injury/activation, manifest by increased endothelin-1 (ET-1), endothelin converting enzyme-1 (ECE1) and intercellular adhesion molecule-1, is uncertain.ObjectiveTo investigate the potential roles of innate immune ligands in both these pathogenic pathways.MethodsThe effect of known Toll-like receptor (TLR) ligands was tested in vitro on dermal microvascular and pulmonary arterial endothelial cells, and on dermal fibroblasts cultured from healthy controls and patients with SSc. To test the effect of double-stranded RNA (dsRNA) on vascular activation/injury in vivo, polyinosinic/polycytidylic acid (poly(I:C)) was administered continuously over 7 days by subcutaneous osmotic pump.ResultsdsRNA/poly(I:C), but not other TLR ligands, highly stimulated ET-1 protein and mRNA (EDN1), as well as intercellular adhesion molecule-1 (ICAM-1) and IFN-regulated MX2, by endothelial cells and dermal fibroblasts. Poly(I:C) induced EDN1, ECE1, and ICAM-1 mRNA expression in poly(I:C) treated skin. Poly(I:C)-induced EDN1, ECE1 and MX2 was not blocked in mice with the type I IFN receptor deleted. However, poly(I:C)-induced EDN1 and ECE1, but not poly(I:C)-induced ICAM-1 expression was blocked in mice with the TLR3 signalling protein TRIF/TICAM-1 deleted.ConclusionTogether these data show that the dsRNA can regulate genes associated with vascular activation, as seen in SSc, that type I IFNs do not mediate these effects, and that EDN1 and ECE1 but not ICAM-1 activation is mediated by TLR3.

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HDL-Mediated Lipid Influx to Endothelial Cells Contributes to Regulating Intercellular Adhesion Molecule (ICAM)-1 Expression and eNOS Phosphorylation

International Journal of Molecular Sciences ◽

10.3390/ijms19113394 ◽

2018 ◽

Vol 19 (11) ◽

pp. 3394 ◽

Cited By ~ 6

Author(s):

Mónica Muñoz-Vega ◽

Felipe Massó ◽

Araceli Páez ◽

Gilberto Vargas-Alarcón ◽

Ramón Coral-Vázquez ◽

...

Keyword(s):

Endothelial Cells ◽

Adhesion Molecule ◽

Hdl Cholesterol ◽

Intercellular Adhesion ◽

Intercellular Adhesion Molecule ◽

High Density Lipoproteins ◽

Type I ◽

Intercellular Adhesion Molecule 1 ◽

Apo Ai

Reverse cholesterol transport (RCT) is considered as the most important antiatherogenic role of high-density lipoproteins (HDL), but interventions based on RCT have failed to reduce the risk of coronary heart disease. In contrast to RCT, important evidence suggests that HDL deliver lipids to peripheral cells. Therefore, in this paper, we investigated whether HDL could improve endothelial function by delivering lipids to the cells. Internalization kinetics using cholesterol and apolipoprotein (apo) AI fluorescent double-labeled reconstituted HDL (rHDL), and human dermal microvascular endothelial cells-1 (HMEC-1) showed a fast cholesterol influx (10 min) and a slower HDL protein internalization as determined by confocal microscopy and flow cytometry. Sphingomyelin kinetics overlapped that of apo AI, indicating that only cholesterol became dissociated from rHDL during internalization. rHDL apo AI internalization was scavenger receptor class B type I (SR-BI)-dependent, whereas HDL cholesterol influx was independent of SR-BI and was not completely inhibited by the presence of low-density lipoproteins (LDL). HDL sphingomyelin was fundamental for intercellular adhesion molecule-1 (ICAM-1) downregulation in HMEC-1. However, vascular cell adhesion protein-1 (VCAM-1) was not inhibited by rHDL, suggesting that components such as apolipoproteins other than apo AI participate in HDL’s regulation of this adhesion molecule. rHDL also induced endothelial nitric oxide synthase eNOS S1177 phosphorylation in HMEC-1 but only when the particle contained sphingomyelin. In conclusion, the internalization of HDL implies the dissociation of lipoprotein components and a SR-BI-independent fast delivery of cholesterol to endothelial cells. HDL internalization had functional implications that were mainly dependent on sphingomyelin. These results suggest a new role of HDL as lipid vectors to the cells, which could be congruent with the antiatherogenic properties of these lipoproteins.

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