l-158,809 and (d-Ala7)-angiotensin I/II (1–7) decrease PAI-1 release from human umbilical vein endothelial cells

Yoshida, Masaya; Naito, Yasuhisa; Urano, Tetsumei; Takada, Akikazu; Takada, Yumiko

doi:10.1016/s0049-3848(02)00056-7

Cited by 20 publications

(10 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies reporting elevated PAI-1 antigen after Ang II stimulation could be related to different endothelial origin [32] or experimental conditions. In fact, a slight but significant increase in Ang II-stimulated HUVEC was only observed with 100 times higher Ang II concentrations [33]. However, our data would agree with a previous study showing that calcium mobilizing agents (as Ang II) may indeed suppress the proinflammatory cytokines-induced increase in PAI-1 synthesis due to impaired protein translation [34].…”

Section: Discussionsupporting

confidence: 90%

Influence of the 4G/5G PAI-1 genotype on angiotensin II-stimulated human endothelial cells and in patients with hypertension

Roncal

Orbe

Rodríguez

et al. 2004

Cardiovascular Research

View full text Add to dashboard Cite

Background: We examined the influence of the 4G/5G PAI-1 (plasminogen activator inhibitor) genotype on Angiotensin II (Ang II)-induced PAI-1 expression by human endothelial cells (HUVEC) in the presence and absence of AT 1 -receptor blocker losartan, and screened for this polymorphism in relation to plasma PAI-1 and arterial pressure in apparently healthy subjects. Methods and results: Genotyped cultured HUVEC were incubated with Ang II (10 À 8 M) with or without losartan up to 24 h. PAI-1 mRNA was determined in cell extracts and protein and activity assessed in supernatants and extracellular matrix (ECM). Ang II increased PAI-1 mRNA and activity in a genotypedependent manner, higher values observed for 4G/4G HUVEC compared with 4G/5G and 5G/5G genotypes ( p < 0.05). Laser confocal microscopy and Western blot analysis showed increased PAI-1 protein within ECM in Ang II-stimulated cultures. PAI-1 expression and protein secretion induced by Ang II in 4G/4G HUVEC was completely inhibited by preincubation with 0.05 AM losartan ( p < 0.01), indicating an AT 1 -mediated effect. In a group of hypertensives homozygous for the 4G allele, PAI-1 antigen was significantly increased (51.0 F 10.1 ng/ml) compared with normotensives (28.3 F 4.0 ng/ml) and hypertensives carrying the 5G allele ( p < 0.05). Conclusions: The 4G/5G PAI-1 polymorphism determines the endothelial PAI-1 upregulation by Ang II and the inhibitory response to losartan. Analysis of PAI-1 genotypes may help identifying subgroups of hypertensives at higher cardiovascular risk.

show abstract

Section: Discussionsupporting

confidence: 90%

Influence of the 4G/5G PAI-1 genotype on angiotensin II-stimulated human endothelial cells and in patients with hypertension

Roncal

Orbe

Rodríguez

et al. 2004

Cardiovascular Research

View full text Add to dashboard Cite

show abstract

“…Partial agonism is a common feature of peptidic antagonists and has also been observed for A-779 in some preparations. 24 Studies in Mastransfected cells ruled out involvement of the other Ang receptors, because these cells do not express AT 1 R or AT 2 R constitutively. Evidence for the involvement of receptor Mas in the NO-releasing activity has also been suggested in in vivo studies using Mas knockout mice.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin-(1-7) Through Receptor Mas Mediates Endothelial Nitric Oxide Synthase Activation via Akt-Dependent Pathways

et al. 2007

View full text Add to dashboard Cite

Abstract-Angiotensin-(1-7) [Ang-(1-7)] causes endothelial-dependent vasodilation mediated, in part, by NO release.However, the molecular mechanisms involved in endothelial NO synthase (eNOS) activation by Ang-(1-7) remain unknown. Using Chinese hamster ovary cells stably transfected with Mas cDNA (Chinese hamster ovary-Mas), we evaluated the underlying mechanisms related to receptor Mas-mediated posttranslational eNOS activation and NO release. We further examined the Ang-(1-7) profile of eNOS activation in human aortic endothelial cells, which constitutively express the Mas receptor. Chinese hamster ovary-Mas cells and human aortic endothelial cell were stimulated with Ang-(1-7; 10 Ϫ7 mol/L; 1 to 30 minutes) in the absence or presence of A-779 (10 Ϫ6 mol/L). Additional experiments were performed in the presence of the phosphatidylinositol 3-kinase inhibitor wortmannin (10 Ϫ6 mol/L). Changes in eNOS (at Ser1177/Thr495 residues) and Akt phosphorylation were evaluated by Western blotting. NO release was measured using both the fluorochrome 2,3-diaminonaphthalene and an NO analyzer. Ang-(1-7) significantly stimulated eNOS activation (reciprocal phosphorylation/dephosphorylation at Ser1177/Thr495) and induced a sustained Akt phosphorylation (PϽ0.05). Concomitantly, a significant increase in NO release was observed (2-fold increase in relation to control). These effects were blocked by A-779. Wortmannin suppressed eNOS activation in both Chinese hamster ovary-Mas and human aortic endothelial cells. Our findings demonstrate that Ang-(1-7), through Mas, stimulates eNOS activation and NO production via Akt-dependent pathways. These novel data highlight the importance of the Ang-(1-7)/Mas axis as a putative regulator of endothelial function. T he renin-angiotensin system is a crucial regulator of cardiovascular homeostasis. Most physiological effects of angiotensin (Ang) II are mediated via Ang II type 1 (AT 1 ) receptors (AT 1 R), with Ang II type 2 (AT 2 ) receptors (AT 2 R) counteracting AT 1 R actions. 1 Growing evidence indicates that the Ang peptide Ang-(1-7) plays an important role in the renin-angiotensin system. 2 This heptapeptide is formed by Ang-converting enzyme-dependent and Ang-converting enzyme-independent pathways. Much attention has been given recently to its formation through hydrolysis of Ang II by the ectoenzyme Ang-converting enzyme 2, which is present in many organs. 3 Ang-(1-7) opposes many Ang II-stimulated actions. Ang-(1-7), acting through the G protein-coupled receptor (GPCR) Mas, releases NO and prostaglandins causing vasodilation, inhibition of cell growth, and opposition of AT 1 R-mediated Ang II vasoconstrictor and proliferative effects. 2 Overactivity of the renin-angiotensin system, as observed in cardiovascular diseases, and the lack of balance among its peptides may reduce NO bioavailability leading to endothelial dysfunction. 4,5 NO plays a critical role in endothelial function, maintaining vasodilator tone, inhibiting platelet aggregation and adhesion, and modulating vascular smooth ...

show abstract

“…Yoshida et al . [95] reported an increase in plasminogen activated inhibitor-1 (PAI-1) and tissue plasminogen activator in cultured human umbilical vein endothelial cells treated with Ang-(1-7). These results suggest that Ang-(1-7) may reduce COX-2 to inhibit lung cancer cell growth as well as provide anti-thrombotic protection against cardiovascular events due to decreased COX-2 in blood vessels.…”

Section: Ang-(1-7) and Lung Cancermentioning

confidence: 99%

Angiotensin Peptides and Lung Cancer

Gallagher¹,

Cook²,

Soto-Pantoja³

et al. 2011

CCDT

View full text Add to dashboard Cite

Lung cancer is a leading cause of death in both men and women, with over 1,000,000 new cases diagnosed worldwide annually and a 5-year survival rate of only 14%, a figure that has improved little in the past thirty years. This poor prognosis suggests a need for novel approaches for the treatment and prevention of lung cancer. The renin-angiotensin system is an established, primary regulator of blood pressure, homeostasis, and natriuresis; however, compelling evidence indicates that the angiotensin peptides also play a role in cell proliferation and inflammation. Angiotensin II is a vasoconstrictor, a mitogen, and an angiogenic factor, while angiotensin-(1-7) has vasodilator, anti-proliferative, and anti-angiogenic properties. This review focuses on studies examining the renin-angiotensin system in pulmonary cancers and whether clinical intervention of this pathway may serve as an effective chemotherapeutic and/or chemopreventive modality for lung cancer.

show abstract

l-158,809 and (d-Ala7)-angiotensin I/II (1–7) decrease PAI-1 release from human umbilical vein endothelial cells

Cited by 20 publications

References 31 publications

Influence of the 4G/5G PAI-1 genotype on angiotensin II-stimulated human endothelial cells and in patients with hypertension

Influence of the 4G/5G PAI-1 genotype on angiotensin II-stimulated human endothelial cells and in patients with hypertension

Angiotensin-(1-7) Through Receptor Mas Mediates Endothelial Nitric Oxide Synthase Activation via Akt-Dependent Pathways

Angiotensin Peptides and Lung Cancer

Contact Info

Product

Resources

About