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, Lynn, Jose, Roby J., Nguyen, Tam, Walker, Philip J. and Golledge, Jonathan (2014) Urocortin 2 is associated with abdominal aortic aneurysm and mediates anti-proliferative effects on vascular smooth muscle cells via corticotrophin releasing factor receptor 2. Clinical Science, 126 7: 517-527. doi:10.1042/CS20130425


Author Emeto, Theophilus I.
Moxon, Joseph V.
Biros, Erik
Rush, Catherine M.
Clancy, Paula
Woodward, Lynn
Moran, Lynn
Jose, Roby J.
Nguyen, Tam
Walker, Philip J.
Golledge, Jonathan
Title Urocortin 2 is associated with abdominal aortic aneurysm and mediates anti-proliferative effects on vascular smooth muscle cells via corticotrophin releasing factor receptor 2
Journal name Clinical Science   Check publisher's open access policy
ISSN 0143-5221
1470-8736
Publication date 2014-01-01
Year available 2013
Sub-type Article (original research)
DOI 10.1042/CS20130425
Volume 126
Issue 7
Start page 517
End page 527
Total pages 16
Place of publication London, United Kingdom
Publisher Portland Press
Language eng
Formatted abstract
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.
Keyword Aneurysm
Corticotrophin releasing factor receptor 2,
Inflammation
Proliferation
Urocortin 2
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online ahead of print: 10 October 2013.

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2014 Collection
School of Medicine Publications
 
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Created: Wed, 11 Dec 2013, 21:52:41 EST by Roheen Gill on behalf of UQ Centre for Clinical Research