scholarly journals Corticotropin releasing hormone receptor 2 antagonist, RQ-00490721, for the prevention of pressure overload-induced cardiac dysfunction

2022 ◽  
Vol 146 ◽  
pp. 112566
Author(s):  
Yu Mori ◽  
Ayako Tsuchihira ◽  
Tatsuya Yoshida ◽  
Satoya Yoshida ◽  
Akiyoshi Fujiuchi ◽  
...  
2017 ◽  
Vol 214 (7) ◽  
pp. 1877-1888 ◽  
Author(s):  
Takuma Tsuda ◽  
Mikito Takefuji ◽  
Nina Wettschureck ◽  
Kazuhiko Kotani ◽  
Ryota Morimoto ◽  
...  

Heart failure occurs when the heart is unable to effectively pump blood and maintain tissue perfusion. Despite numerous therapeutic advancements over previous decades, the prognosis of patients with chronic heart failure remains poor, emphasizing the need to identify additional pathophysiological factors. Here, we show that corticotropin releasing hormone receptor 2 (Crhr2) is a G protein–coupled receptor highly expressed in cardiomyocytes and continuous infusion of the Crhr2 agonist, urocortin 2 (Ucn2), reduced left ventricular ejection fraction in mice. Moreover, plasma Ucn2 levels were 7.5-fold higher in patients with heart failure compared to those in healthy controls. Additionally, cardiomyocyte-specific deletion of Crhr2 protected mice from pressure overload-induced cardiac dysfunction. Mice treated with a Crhr2 antagonist lost maladaptive 3′-5′-cyclic adenosine monophosphate (cAMP)–dependent signaling and did not develop heart failure in response to overload. Collectively, our results indicate that constitutive Crhr2 activation causes cardiac dysfunction and suggests that Crhr2 blockade is a promising therapeutic strategy for patients with chronic heart failure.


2011 ◽  
Vol 44 (06) ◽  
Author(s):  
K Lerche ◽  
M Willem ◽  
K Kleinknecht ◽  
C Romberg ◽  
U Konietzko ◽  
...  

2013 ◽  
Vol 30 (12) ◽  
pp. 1161-1169 ◽  
Author(s):  
Erika J. Wolf ◽  
Karen S. Mitchell ◽  
Mark W. Logue ◽  
Clinton T. Baldwin ◽  
Annemarie F. Reardon ◽  
...  

Peptides ◽  
2009 ◽  
Vol 30 (12) ◽  
pp. 2483-2486 ◽  
Author(s):  
Keisuke Maruyama ◽  
Kohei Wada ◽  
Kotaro Ishiguro ◽  
Sei-Ichi Shimakura ◽  
Tatsuya Wakasugi ◽  
...  

1997 ◽  
Vol 8 (12) ◽  
pp. 944-945 ◽  
Author(s):  
J. Shonee Lesh ◽  
Heather L. Burrows ◽  
Audrey F. Seasholtz ◽  
Sally A. Camper

2001 ◽  
Vol 48 (1) ◽  
pp. 1-9 ◽  
Author(s):  
KOZO HASHIMOTO ◽  
SHINYA MAKINO ◽  
KOICHI ASABA ◽  
MITSURU NISHIYAMA

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