Urocortin 2 is associated with abdominal aortic aneurysm and mediates anti-proliferative effects on vascular smooth muscle cells via corticotrophin releasing factor receptor 2

EMETO, Theophilus I.; MOXON, Joseph V.; BIROS, Erik; RUSH, Catherine M.; CLANCY, Paula; WOODWARD, Lynn; MORAN, Corey S.; JOSE, Roby J.; NGUYEN, Tam; WALKER, Philip J.; GOLLEDGE, Jonathan
April 2014
Clinical Science;Apr2014, Vol. 126 Issue 7/8, p517
Academic Journal
AAA (abdominal aortic aneurysm) is an important cause of sudden death in older adults, but there is no current effective drug therapy for this disease. The UCNs (urocortins1-3) and their receptors: CRFR (corticotrophin-releasing factor receptor)-1 and -2 have been implicated in various CVDs (cardiovascular diseases). We assessed the relative expression of UCN1-3 in AAA by qRT-PCR (quantitative reverse transcription-PCR) and ELISA, and examined in vitro how UCN2 affects human aortic VSMC (vascular smooth muscle cell) Akt phosphorylation, pro-inflammatory cytokine IL (interleukin)-6 secretion, proliferation, cell cycle and apoptosis. UCN2 and CRFR2 expression were significantly up-regulated in biopsies from the AAA body. AAA body biopsies released high amounts of UCN2 in vitro. Median plasma UCN2 concentrations were 2.20 ng/ml (interquartile range 1.14-4.55 ng/ml, n=67) in AAA patients and 1.11 ng/ml (interquartile range 0.76-2.55 ng/ml, n=67) in patients with non-aneurysmal PAD (peripheral artery disease) (P=0.001). Patients with UCN2 in the highest quartile had a 4.12-fold (95% confidence interval, 1.37-12.40) greater prevalence of AAA independent of other risk factors, P=0.012. In vitro, UCN2 significantly inhibited VSMC Akt phosphorylation and proliferation in a dose-dependent manner. UCN2 induced VSMC G1 cell-cycle arrest and increased IL-6 secretion over 24 h. The CRFR2 antagonist astressin-2B significantly abrogated the effects of UCN2 on VSMCs. In conclusion, UCN2 is significantly associated with AAA and inhibits VSMC proliferation by inducing a G1 cell cycle arrest suggesting a plausible regulatory role in AAA pathogenesis.


Related Articles

  • Myosin light chain kinase controls voltage-dependent calcium channels in vascular smooth muscle. Martinsen, A.; Schakman, O.; Yerna, X.; Dessy, C.; Morel, N. // Pflugers Archiv European Journal of Physiology;Jul2014, Vol. 466 Issue 7, p1377 

    The Ca-dependent kinase myosin light chain kinase (MLCK) is the activator of smooth muscle contraction. In addition, it has been reported to be involved in Ca channel regulation in cultured cells, and we previously showed that the MLCK inhibitor ML-7 decreases arginine vasopressin (AVP)-induced...

  • β-Catenin overexpression in malignant glioma and its role in proliferation and apoptosis in glioblastma cells. Xiangrong Liu; Lei Wang; Shangfeng Zhao; Xunming Ji; Yumin Luo; Feng Ling // Medical Oncology;Jun2011, Vol. 28 Issue 2, p608 

    β-Catenin, a core component of Wnt/β-catenin signaling, has been shown to be a crucial factor in a broad range of tumors, while its role in glioma is not well understood. In this study, the expression of β-catenin in astrocytic glioma tissues with different grade and human normal...

  • Different Effects of Angiotensin II and Angiotensin-(1-7) on Vascular Smooth Muscle Cell Proliferation and Migration. Santini, Emanuela; Sgambato-Faure, Veronique; Qin Li; Savasta, Marc; Dovero, Sandra; Fisone, Gilberto; Bezard, Erwan // PLoS ONE;2010, Vol. 5 Issue 8, p1 

    Background: Angiotensin (Ang) II and Ang-(1-7) are two of the bioactive peptides of the rennin-angiotensin system. Ang II is involved in the development of cardiovascular disease, such as hypertension and atherosclerosis, while Ang-(1-7) shows cardiovascular protection in contrast to Ang II....

  • Differentiation patterning of vascular smooth muscle cells (VSMC) in atherosclerosis. Matthias Ocker; Andrea Hartner; Kerstin Amann; Letterio Barbera // Virchows Archiv;Aug2009, Vol. 455 Issue 2, p171 

    Abstract  To investigate the involvement of transdifferentiation and dedifferentiation phenomena inside atherosclerotic plaques, we analyzed the differentiation status of vascular smooth muscle cells (VSMC) in vitro and in vivo. Forty normal autoptic and 20 atherosclerotic carotid...

  • Influence of paeonol on expression of COX-2 and p27 in HT-29 cells. Jun-Mei Ye; Tao Deng; Jian-Bao Zhang; Jian-Ying Wang // World Journal of Gastroenterology;9/21/2009, Vol. 15 Issue 35, p4410 

    AIM: To investigate the effect of paeonol on controlling the proliferation of colorectal cancer cell line HT-29 and to discuss its possible mechanism. METHODS: The inhibitory effect of paeonol on proliferation of HT-29 cells was detected by MTT assay. The results of apoptosis were measured by...

  • miR-874 Inhibits cell proliferation, migration and invasion through targeting aquaporin-3 in gastric cancer. Jiang, Baofei; Li, Zengliang; Zhang, Wenjie; Wang, Haixiao; Zhi, Xiaofei; Feng, Jin; Chen, Zheng; Zhu, Yi; Yang, Li; Xu, Hao; Xu, Zekuan // Journal of Gastroenterology;Jun2014, Vol. 49 Issue 6, p1011 

    Background: Aquaporin-3 (AQP3) is a water transporting protein which plays an oncogenic role in several malignant tumors. However, its regulatory mechanism remains elusive to date. In this study, we investigated the microRNA-mediated gene repression mechanism involved in AQP3's role. Methods:...

  • Decorin-Mediated Inhibition of Human Trophoblast Cells Proliferation, Migration, and Invasion and Promotion of Apoptosis In Vitro. Yanfen Zou; Xiang Yu; Jing Lu; Ziyan Jiang; Qing Zuo; Mingsong Fan; Shiyun Huang; Lizhou Sun; Zou, Yanfen; Yu, Xiang; Lu, Jing; Jiang, Ziyan; Zuo, Qing; Fan, Mingsong; Huang, Shiyun; Sun, Lizhou // BioMed Research International;1/1/2015, Vol. 2015, p1 

    Preeclampsia (PE) is a unique complication of pregnancy, the pathogenesis of which has been generally accepted to be associated with the dysfunctions of extravillous trophoblast (EVT) including proliferation, apoptosis, and migration and invasion. Decorin (DCN) has been proved to be a...

  • MicroRNA-711 is a prognostic factor for poor overall survival and has an oncogenic role in breast cancer. JING-YE HU; WEI YI; MEI-YIN ZHANG; RUI XU; LI-SI ZENG; XIAO-RAN LONG; XIAO-MIN ZHOU; XIAO-FENG STEVEN ZHENG; YIBIN KANG; HUI-YUN WANG // Oncology Letters;Mar2016, Vol. 11 Issue 3, p2155 

    MicroRNAs are important in cancer development and progression. In the present study, the clinical significance and function of microRNA-711 (miR-711) expression in breast cancer were investigated. The expression level of miR-711 was analyzed in breast cancer tissue samples using reverse...

  • A novel gene RNF138 expressed in human gliomas and its function in the glioma cell line U251. Zhou, You-xin; Chen, San-song; Wu, Ting-feng; Ding, Da-dong; Chen, Xiong-hui; Chen, Jin-ming; Su, Zuo-peng; Li, Bin; Chen, Gui-lin; Xie, Xue-shun; Dai, Yan-fang; Wei, Yong-xin; Du, Zi-wei // Analytical Cellular Pathology: Cellular Oncology;2012, Vol. 35 Issue 3, p167 

    Background: The gliomas represent the most common primary malignant brain tumors; however, little is known about the molecular pathogenesis of these tumors. Recent research reveals that the oncogenesis and development of gliomas have a close relation to the overexpression of several oncogenes...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics