Cellular distribution of immunoreactive urotensin-II in human tissues with evidence of increased expression in atherosclerosis and a greater constrictor response of small compared to large coronary arteries

Maguire, Janet J.; Kuc, Rhoda E.; Wiley, Katherine; Kleinz, Matthias J.; Davenport, Anthony P.

doi:10.1016/j.peptides.2004.01.028

Cited by 104 publications

(106 citation statements)

References 22 publications

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“…UII and its receptor are known to be upregulated in atherosclerotic plaque from non-diabetic animals and human patients [9][10][11]. Additionally, chronic UII infusion has been shown to enhance macrophage foam cell formation [12] and atherosclerosis in high-fat-fed Apoe knockout (KO) mice [13].…”

Section: Introductionmentioning

confidence: 99%

Urotensin II receptor antagonism confers vasoprotective effects in diabetes associated atherosclerosis: studies in humans and in a mouse model of diabetes

et al. 2013

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Aims/hypothesis The small, highly conserved vasoactive peptide urotensin II (UII) is upregulated in atherosclerosis. However, its effects in diabetes-associated atherosclerosis have not been assessed. Methods Endothelial cells were grown in normal-and highglucose (5 and 25 mmol/l) media with and without UII (10 −8 mol/l) and/or the UII receptor antagonist, SB-657510 (10 −8 mol/l). Apoe knockout (KO) mice with or without streptozotocin-induced diabetes were treated with or without SB-657510 (30 mgkg −1 day −1 ; n=20 per group) and followed for 20 weeks. Carotid endarterectomy specimens from diabetic and non-diabetic humans were also evaluated. Results In high (but not normal) glucose medium, UII significantly increased CCL2 (encodes macrophage chemoattractant protein 1 [MCP-1]) gene expression (human aortic endothelial cells) and increased monocyte adhesion (HUVECs). UII receptor antagonism in diabetic Apoe KO mice significantly attenuated diabetes-associated atherosclerosis and aortic staining for MCP-1, F4/80 (macrophage marker), cyclooxygenase-2, nitrotyrosine and UII. UII staining was significantly increased in carotid endarterectomies from diabetic compared with non-diabetic individuals, as was staining for MCP-1. Conclusions/interpretation This is the first report to demonstrate that UII is increased in diabetes-associated atherosclerosis in humans and rodents. Diabetes-associated plaque development was attenuated by UII receptor antagonism in the experimental setting. Thus UII may represent a novel therapeutic target in the treatment of diabetes-associated atherosclerosis.

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Section: Introductionmentioning

confidence: 99%

Urotensin II receptor antagonism confers vasoprotective effects in diabetes associated atherosclerosis: studies in humans and in a mouse model of diabetes

et al. 2013

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“…Expression of U-II and UT receptor has been reported in kidney, CNS, and in the cardiovascular system (10 -14). Pharmacological studies have shown that U-II exerts potent vasoactive activity in different mammal species, including humans and rats (13,(15)(16)(17)(18)(19). The contractile activity of U-II is mediated by the activation the small GTPase RhoA and its effector, Rho kinase (20).…”

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confidence: 99%

Urotensin II is a New Chemotactic Factor for UT Receptor-Expressing Monocytes

Segain

Rolli–Derkinderen

Gervois

et al. 2007

The Journal of Immunology

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Urotensin II (U-II), a vasoactive cyclic neuropeptide which activates the G protein-coupled receptor UT receptor, exerts various cardiovascular effects and may play a role in the pathophysiology of atherosclerosis. In this study, we report that the UT receptor is expressed and functional on human PBMC and rat splenocytes. PBMC surface expression of the UT receptor was mainly found in monocytes and NK cells, also in a minority of B cells, but not in T cells. Stimulation of monocytes with LPS increased UT receptor mRNA and protein expression. Cloning and functional characterization of the human UT receptor gene promoter revealed the presence of NF-κB-binding sites involved in the stimulation of UT receptor gene expression by LPS. Activation of the UT receptor by U-II induced chemotaxis with maximal activity at 10 and 100 nM. This U-II effect was restricted to monocytes. Analysis of the signaling pathway involved indicated that U-II-mediated chemotaxis was related to RhoA and Rho kinase activation and actin cytoskeleton reorganization. The present results thus identify U-II as a chemoattractant for UT receptor-expressing monocytes and indicate a pivotal role of the RhoA-Rho kinase signaling cascade in the chemotaxis induced by U-II.

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“…Bunların yanı sıra plateletlerdeki serotoninin (5-HT) ÜT 2 ile vasküler düz kas hücre proliferasyonunu arttırmak için sinerjistik etkileşim gösterdiği ve hipertansif vasküler hastalıkta aterosklorozun hızlı gelişimine katkıda bulunduğu söylenmiştir [70]. ÜT 2 ekspresyonu aynı zamanda aterosklorotik plaklarda vaskü-ler düz kas hücre proliferasyonunu stimule edebilir, daha da fazlası ÜT 2 lokal olarak koroner vazokonstriksiyona neden olabilir ve myokard iskemisini attırabilir [71]. Aterosklorozla ile ilgili yapılan deneysel çalışmalara baktığımız-da ise; Suguro ve arkadaşları [72] yaptığı bir çalışmada hipertansif hastalarda artan ÜT 2 seviyelerinin karotid aterosklerozunun gelişmesinde çok önemli bir rol oynadığını göstermişlerdir.…”

Section: Aterosklerozunclassified

The Importence of Urotensin and Urotensin Receptors in Cardiovascular System

Köse¹

2014

Ann Clin Anal Med

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ÖzetBir siklik petid olan Ürotensin 2 (ÜT 2) yaklaşık 45 yıl önce keşfedilmiştir ve güçlü vazokonstriktör etkilerinin olmasından dolayı bilim camiası tarafından dikkat çekmiştir. ÜT 2 G proteinine bağlı bir reseptör olan "GPR14" reseptö-rüne bağlanarak etki gösterir. ÜT 2 ve reseptörü yaygın olarak periferik vasküler dokularda, kalp ve böbrekte dağılım göstermektedir. ÜT 2'nin sağlıklı insanda çok küçük bir role sahip olduğu belirtilmiş, hastalık durumlarında ise nispeten rolünün daha belirgin olduğuna değinilmiştir. ÜT 2'nin kardiyovaskü-ler etkileri insanda başlıca pozitif inotropi, vazokontsriksiyon ve vasküler yatağın ve endotelin durumuna bağlı vazodilatasyon ve vasküler düz kas hücre proliferasyonudur. Günümüzdeki araştırmalar ÜT 2'nin özellikle çeşitli kardiyovasküler hastalıklarda önemli bir rol oynadığını göstermiştir. ÜT 2 ve dolayısıyla ÜT 2 reseptörlerinin kardiyovasküler sistem üzerindeki etkileri günü-müzde oldukça çok çalışılan bir konu olmakla beraber literatürde bu konuyla ilgili çalışmalar ve bu çalışmalar sonucu elde edilen sonuçlar oldukça karı-şıktır. Kalp yetmezliğinde daha önceki çalışmalarda majör bir rol oynamadığı söylenmiş, daha sonraki çalışmalarda hastalığın patofizyolojisinde potansiyel role sahip olduğu gösterilmiştir. Ayrıca koroner kalp hastalığı ve iskemik kalp hastalığı ve aterosklerozda da ÜT 2 seviyesinin arttığı gösterilmiştir. Bu reseptörlerin fizyopatolojide mi rol oynadığı veya çok önemli bir savunma makanizması mı olduğu önemli bir araştırma konusu olmaktadır. Bu nedenle bu reseptörler bilim camiasında umut verici bir hedef olarak değerlendirilmekte-dir. Sonuç olarak bu reseptörlerin ileride çoğu hastalıkta özellikle kardiyovasküler hastalıkların gerek patofizyolojisi gerekse savunma mekanizmalarında kendilerine yer edineceğini ve daha fazla önem kazanacağını düşünmekteyiz. Anahtar KelimelerÜrotensin-2; Ürotensin Reseptörü; Endotel; Kalp Yetmezliği; Hipertansiyon Abstract Urotensin 2 (UT 2) which is a cyclic peptid was first identified about 45 years ago and due to its potent vasoconstrictor effect it has attracted the attention of the scientific community. UT 2 binds to a class of G protein-coupled receptor known as GPR14. Receptors for UT 2 are located on peripheral vascular smooth muscle, heart and kidney. In healthy people it has minor role, while in patients with disease it has a more prominent role. Main positive effects of UT 2 in cardiovasculer system are positive inotropic effect, vasoconsctruction, vascular smooth muscle cell proliferation, vasodilatation which related the state of endothelin and vascular bed. Recent investigations have showed that UT 2 plays an important role in cardiovascular diseases. Although the effects of UT 2 and UT 2 receptors on cardiovascular system is a quite extensively studied subject. The studies and the results obtained from these studies are somewhat complex. Previous studies in heart failure has demonstrated that these receptors do not play a major role in heart failure but in later studies it has been shown that these receptor...

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Cellular distribution of immunoreactive urotensin-II in human tissues with evidence of increased expression in atherosclerosis and a greater constrictor response of small compared to large coronary arteries

Cited by 104 publications

References 22 publications

Urotensin II receptor antagonism confers vasoprotective effects in diabetes associated atherosclerosis: studies in humans and in a mouse model of diabetes

Urotensin II receptor antagonism confers vasoprotective effects in diabetes associated atherosclerosis: studies in humans and in a mouse model of diabetes

Urotensin II is a New Chemotactic Factor for UT Receptor-Expressing Monocytes

The Importence of Urotensin and Urotensin Receptors in Cardiovascular System

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