Disease relevance of EDN1

• Here we show that red wines strongly inhibit the synthesis of endothelin-1, a vasoactive peptide that is crucial in the development of coronary atherosclerosis [1].
• Because of the potential role of ET-1 in vascular disorders such as hypertension and atherosclerosis, we investigated the regulation of ET-1 expression by PPAR activators [2].
• From these observations, we propose that hypoxia-activated AdvFBs exhibit pro-angiogenic properties and, as such, communicate with VVECs, in a process involving ET-1, to regulate vasa vasorum neovascularization occurring in the adventitia of pulmonary arteries in response to chronic hypoxia [3].
• Hyperglycemia has been postulated to increase ET-1 secretion in endothelial cells [4].
• These findings suggest that endothelin is a regulator of the contractile properties of pericytes, which may be adversely affected in diabetic retinopathy [5].

Psychiatry related information on EDN1

• As PGF2alpha directly stimulated Ang II release, Ang II may influence the critical period for starting the cascade of functional luteolysis in vivo and might lead to structural luteolysis with ET-1 as a major vasoconstrictor [6].

High impact information on EDN1

• ECE-1: a membrane-bound metalloprotease that catalyzes the proteolytic activation of big endothelin-1 [7].
• Endothelin-1 (ET-1), a 21-residue vasoactive peptide, is produced in vascular endothelial cells from the 38-residue inactive intermediate big endothelin-1 via a specific cleavage at Trp-21-Val-22 [7].
• When transfected into cultured cells that normally secrete only big ET-1, the ECE-1 cDNA conferred the ability to secrete mature ET-1 [7].
• Verotoxin and ricin have novel effects on preproendothelin-1 expression but fail to modify nitric oxide synthase (ecNOS) expression and NO production in vascular endothelium [8].
• We investigated the effects of Atorvastatin and Simvastatin on the pre-proET-1 mRNA expression and ET-1 synthesis and on the endothelial NO synthase (eNOS) transcript and protein levels in bovine aortic endothelial cells [9].

Chemical compound and disease context of EDN1

• Overexpression of PKC-beta1 and -delta isoforms but not PKC-zeta isoform by adenovirus vectors containing the respective cDNA enhanced in parallel PKC activities, proteins, and basal and glucose-induced ET-1 mRNA expression by at least 2-fold [4].
• 6. Pretreatment with pertussis toxin reduced ET-1 stimulated activation of MAP kinase particularly at later times (60 min), but left the responses to both PDGF and BK unaffected [10].
• STUDY DESIGN: The effects of 2% plasma from 12 patients with preeclampsia and 12 normal pregnant women on prostacyclin, nitric oxide, and endothelin production by cultured endothelial cells were measured in the presence or absence of cyclic stretch and laminar shear stress [11].
• Hypoxia increases endothelin release in bovine endothelial cells in culture, but epinephrine, norepinephrine, serotonin, histamine and angiotensin II do not [12].
• Effects of nitric oxide donors and nitric oxide synthase substrates on ciliary muscle contracted by carbachol and endothelin for possible use in myopia prevention [13].

Biological context of EDN1

• Nucleotide sequence of endothelin cDNA from bovine endothelial cells [14].
• To elucidate the cellular mechanism of endothelin-1 biosynthesis induced by angiotensin and vasopressin, we first cloned and sequenced full-length bovine preproendothelin-1 complementary DNA (cDNA) from a cultured bovine carotid artery endothelial cell cDNA library [15].
• Moreover, this study illustrated the in vivo relationships in intraluteal release among PGF(2alpha), ET-1, and Ang II during spontaneous luteolysis in the cow [16].
• However, the phorbol-induced ET-1 decrease was, unlike the shear-induced down-regulation, independent of active protein synthesis [17].
• Neither the transcription factor AP-1 binding site nor the GATA-2-factor binding site, necessary for the basal level of transcription of ET-1 gene, is sufficient to confer shear-responsiveness to the reporter gene [17].

Anatomical context of EDN1

• This is the first evidence of involvement of these pathways on the Endothelin-1 mechanism of action on the blood-brain barrier [18].
• Our results indicate that low concentrations of human HDL strongly stimulate the production of ET-1, a powerful vasoconstrictor and mitogen for the vascular smooth muscle cell [19].
• Endothelin-1 enhanced neutrophil accumulation in the isolated rabbit heart by 4.2 times throughout a TS1/18-inhibitable mechanism [20].
• A phosphoramidon-sensitive, membrane-bound metalloprotease that cleaves big endothelin 1 (big-ET-1) to ET-1 was obtained from human umbilical vein endothelial cells and also from bovine aortic endothelial cells by isolation of plasma-membrane vesicles free of lysosomes [21].
• Identification of endothelin 1 and big endothelin 1 in secretory vesicles isolated from bovine aortic endothelial cells [22].

Associations of EDN1 with chemical compounds

• Interestingly, PGF 2alpha did not alter either CCL2 or EDN1 secretion, regardless of culture conditions (P > 0.05) [23].
• Real-time relationships in intraluteal release among Prostaglandin F2alpha, endothelin-1, and angiotensin II during spontaneous luteolysis in the cow [16].
• In high glucose and 50 micromol/l Hcy, ET-1 mRNA levels were maximal after 1 h (p < 0.05) [24].
• Endothelin-1 decreases ethanolamine plasmalogen levels and evokes PAF production in brain microvessels [18].
• Homocysteine-induced endothelin-1 release is dependent on hyperglycaemia and reactive oxygen species production in bovine aortic endothelial cells [24].

Enzymatic interactions of EDN1

• This study shows that both PPAR-alpha (Wy 14643) and PPAR-gamma activation (rosiglitazone) partially inhibit oxidized LDL-induced protein kinase C activity and endothelin-1 secretion in endothelial cells at the transcriptional levels and suggests that synthetic PPAR activators are stronger PPAR activators than oxidized LDL [25].

Regulatory relationships of EDN1

• Peroxisome proliferator-activated receptor activators inhibit thrombin-induced endothelin-1 production in human vascular endothelial cells by inhibiting the activator protein-1 signaling pathway [2].
• Atrial natriuretic peptide inhibits the production and secretion of endothelin from cultured endothelial cells. Mediation through the C receptor [26].
• Dehydroepiandrosterone Mimics Acute Actions of Insulin to Stimulate Production of Both Nitric Oxide and Endothelin 1 via Distinct Phosphatidylinositol 3-Kinase- and Mitogen-Activated Protein Kinase-Dependent Pathways in Vascular Endothelium [27].
• Northern blot analysis revealed that parathyroid hormone-related protein (1-34) inhibited both basal and thrombin-induced endothelin-1 gene expression [28].
• Inhibitory effect of adrenomedullin on basal and tumour necrosis factor alpha-stimulated endothelin-1 synthesis in bovine aortic endothelial cells is independent of cyclic AMP [29].

Other interactions of EDN1

• EC cocultured with concanavalin A-activated PBMC (ActPBMC) increased CCL2 secretion an average of 12-fold higher compared with controls (P < 0.05), but again, EDN1 secretion was unchanged (P > 0.05) [23].
• Thus, we investigated the local secretion of PGF(2alpha), ET-1, and Ang II in the corpus luteum (CL) and their real-time relationships during spontaneous luteolysis in the cow [16].
• These findings suggest that the vasodilating property of parathyroid hormone-related protein may be mediated in part through its inhibitory effect on endothelin-1 production, which is probably mediated through nitric oxide and cGMP in endothelial cells [28].
• It is concluded that arginine vasopressin and angiotensin II stimulate the release of endothelin-1 by a common mechanism, involving receptor-mediated mobilization of intracellular Ca2+ and activation of protein kinase C in endothelial cells [30].
• The effects of tumor necrosis factor-alpha (TNF-alpha) on the production of the vasoactive substances nitric oxide (NO) and endothelin-1 (ET-1) were investigated in cerebrovascular cells in culture [31].

Analytical, diagnostic and therapeutic context of EDN1

• Basal secretion of EDN1 by EC was substantial (approximately 2 ng/ml), but was not affected by coculture with PBMC (P > 0.05) [23].
• The concentrations of PGF(2alpha), ET-1, Ang II, and progesterone (P) in the MDS samples were determined by enzyme immunoassays [16].
• The enzyme was characterized by RIA with an antibody specific for ET-1 and also by reverse-phase HPLC [21].
• Morphological examination of the ET-1-enriched fraction by electron microscopy identified clusters of vesicles approximately 100 nm in diameter [22].
• Vesicles containing endothelin 1 (ET-1) were isolated from bovine aortic endothelial cells (BAECs) by fractionation of homogenates on sucrose density gradients by ultracentrifugation [22].

References