Plasma urotensin II in heart failure

Richards, A. Mark; Nicholls, M. Gary; Lainchbury, John G.; Fisher, Stephen; Yandle, Timothy G.

doi:10.1016/s0140-6736(02)09709-x

Cited by 159 publications

(102 citation statements)

References 5 publications

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“…The observation that basal hemodynamics and general vasopressor responsiveness are unaltered in UT knockout mice supports the suggestion that the receptor is functionally silent under basal conditions, but this may change in cardiovascular diseases (13). In addition to elevated levels in patients with heart failure, systemic hypertension, diabetes mellitus, and renal failure (14,15), increased plasma UII levels have been reported in patients with cirrhosis (16,17).…”

Section: Introductionsupporting

confidence: 65%

“…To address the issue of UII in the pathogenesis of portal hypertension, our group determined UII levels in patients with cirrhosis without hepatorenal syndrome, systemic hypertension, diabetes and hemodynamic instability secondary to variceal bleeding. UII levels in patients with heart failure, systemic hypertension, diabetes mellitus and renal failure are elevated (14,15), therefore, patients with diabetes mellitus, chronic kidney disease, systemic hypertension, and aortic valvular disease were excluded. UII circulates in the human plasma and its concentration is measured by ELISA using specific antibodies.…”

Section: Discussionmentioning

confidence: 99%

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Increased expression of urotensin II and GPR14 in patients with cirrhosis and portal hypertension

Liu

Chen²,

Wang³

et al. 2010

Int J Mol Med

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Abstract. Urotensin II (UII) and its receptor (UT or GPR14) are involved in liver fibrosis and portal hypertension. Nevertheless, expression of the UII/UT system in the liver of patients with portal hypertension has not been elucidated. UII and UT gene expression were quantified in liver biopsy samples from patients with hepatitis-B-virus-associated cirrhosis and portal hypertension, and from normal controls by using quantitative real-time PCR. The liver distribution of UT was determined by means of immunohistochemistry and immunofluorescence. Western blot analysis was used to assess liver levels of UT. Simultaneously, we measured intraoperative free portal venous pressure (FPVP) and collected plasma for UII measurement by ELISA. UT expression at the mRNA and protein level was enhanced significantly in the liver of patients with cirrhosis and portal hypertension, compared with that in healthy controls. UT protein expression was concentrated mainly in the Kupffer cells and sinusoidal endothelial cells. In cirrhotic tissue, UII gene expression was increased 5-fold in comparison to that in normal liver tissue. Plasma UII level was higher in cirrhotic patients compared with controls and was correlated with FPVP (r=0.807; P<0.001) and UII mRNA in the liver (r=0.802; P<0.001). These findings suggest that the intrahepatic UII/UT system has an important pathophysiological role in cirrhosis and portal hypertension.

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Section: Introductionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Increased expression of urotensin II and GPR14 in patients with cirrhosis and portal hypertension

Liu

Chen²,

Wang³

et al. 2010

Int J Mol Med

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“…Alternatively, in certain pathological conditions including diabetes (24)(25)(26)(27)50), the plasma concentrations of UII may attain much higher levels (140-420 pg/ml) that are in the same range as the IC 50 value (120 pmol/l i.e. 167 pg/ml) calculated for the insulinostatic activity of UII, suggesting that UII might constitute a diabetogenic factor.…”

Section: Discussionmentioning

confidence: 87%

“…Immunoreactive UII is readily measurable in human plasma, and the circulating levels of UII are elevated in patients with chronic renal failure (24) and heart failure (25,26). Plasma UII levels are also increased in diabetic patients with or without proteinuria, but are not correlated with fasting blood glucose or HbA1c levels (27).…”

Section: Introductionmentioning

confidence: 99%

Urotensin-II is present in pancreatic extracts and inhibits insulin release in the perfused rat pancreas

Silvestre

Egido

Hernández

et al. 2004

European Journal of Endocrinology

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Objective: Previous work from our laboratory has demonstrated that frog urotensin-II (UII), at a high concentration, inhibits glucose-induced insulin release in the rat pancreas. We have investigated the effect of rat UII and two structural analogs on insulin secretion and searched for the presence of UII-immunoreactivity in rat pancreatic extracts. Methods: The study was performed in the perfused rat pancreas. UII as well as its analogs were synthesized by solid phase methodology. Pancreatic extracts were analyzed for UII by reversed-phase HPLC combined with a sensitive UII RIA. Results: Infusion of synthetic rat UII inhibited glucose-induced insulin release in a dose-dependent manner (IC 50 : 0.12 nmol/l). UII (1 nmol/l) also inhibited the insulin responses induced by carbachol, glucagon-like peptide-1, and a calcium channel agonist (BAY K 8644). The inhibitory effect of UII was mimicked by the potent G protein-coupled receptor (GPR14) agonist [3-iodo-Tyr 6 ]UII(4 -11). In contrast, [Ala 8 ]UII(4 -11), a UII analog devoid of contractile activity on rat aortic rings, did not affect glucose-induced insulin secretion. Analysis of rat pancreatic extracts revealed the presence of an immunoreactive peptide exhibiting the same retention time as synthetic rat UII.Conclusions: Our results demonstrate that UII is a potent insulinostatic peptide. The observation that UII is actually present in the pancreas suggests that this peptide may play a physiological role in the control of insulin secretion. Concerning the two UII analogs tested, only ]UII(4 -11), reportedly possessing GPR14-mediated contractile activity, mimics the insulinostatic effect of UII. This finding would support the view that UII acts on the pancreatic beta cell through the GPR14 receptor.European Journal of Endocrinology 151 803-809

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“…İn vitro kültüre edilmiş neonatal rat kardiyomyositlerinde hipertrofinin ÜT 2 tarafından arttırıldığı görülmüştür [18,56,57]. Bununla birlikte kardiyak myositlerin hipertrofisinin epidermal büyüme faktörü reseptörüne bağlı sinyal yollarındaki mitojenle aktive edilmiş pro- [44] 3290 pg/ml (istirahatte) 2990 pg/ml (istirahatte) [52] Akut miyokart infarktüsü 0.58 pg/ml (0.42 fmol/l) 1.94 pg/ml (1.40 fmol/ml) [74] Konjestif kalp yetmezliği 4.35 pg/ml 1.41 pg/ml [54] Koroner kalp hastalığı 3.20 pg/ml 1.61 pg/ml [75] Akut koroner sendrom 3300 pg/ml 3450 pg/ml (stabil arter hastalığı) 2530 pg/ml (akut koroner sendrom) [60] Kalp yetmezliği 2.6 pg/ml (1.9 pmol/l) 5.4 pg/ml (3.9 pmol/l) [76] Konjenital kalp hastalığı (çocuk)…”

Section: Koroner Kalp Hastalığı Ve İskemik Kalp Hastalığıunclassified

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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Plasma urotensin II in heart failure

Cited by 159 publications

References 5 publications

Increased expression of urotensin II and GPR14 in patients with cirrhosis and portal hypertension

Increased expression of urotensin II and GPR14 in patients with cirrhosis and portal hypertension

Urotensin-II is present in pancreatic extracts and inhibits insulin release in the perfused rat pancreas

The Importence of Urotensin and Urotensin Receptors in Cardiovascular System

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