• Log in with Facebook Log in with Twitter Log In with Google      Sign In    
  • Create Account
  LongeCity
              Advocacy & Research for Unlimited Lifespans

Photo

Exogenous supplement of glucagon like peptide-1 protects the heart against aortic banding induced myocardial fibrosis...

mtor autophagy liraglutide rapamycin

  • Please log in to reply
No replies to this topic

#1 Zaul

  • Guest
  • 104 posts
  • 11
  • Location:unknown

Posted 12 July 2020 - 05:33 PM


 

 

  Exogenous supplement of glucagon like peptide-1 protects the heart against aortic banding induced myocardial fibrosis and dysfunction through inhibiting mTOR/p70S6K signaling and promoting autophagy
Abstract:

Mammalian target of rapamycin (mTOR) and a ribosomal protein S6 kinase (p70S6K) mediate tissue fibrosis and negatively regulate autophagy. This study aims to investigate whether glucagon-like peptide-1 (GLP-1) analog liraglutide protects the heart against aortic banding-induced cardiac fibrosis and dysfunction through inhibiting mTOR/p70S6K signaling and promoting autophagy activity. Male SD rats were randomly divided into four groups (n = 6/each group): sham operated control; abdominal aortic constriction (AAC); liraglutide treatment during AAC (0.3 mg/kg, injected subcutaneously twice daily); rapamycin treatment during AAC (0.2 mg/kg/day, administered by gastric gavage). Relative to the animals with AAC on week 16, liraglutide treatment significantly reduced heart/body weight ratio, inhibited cardiomyocyte hypertrophy, and augmented plasma GLP-1 level and tissue GLP-1 receptor expression. Phosphorylation of mTOR/p70S6K, populations of myofibroblasts and synthesis of collagen I/III in the myocardium were simultaneously inhibited. Furthermore, autophagy regulating proteins: LC3-II/LC3-I ratio and Beclin-1 were upregulated, and p62 was downregulated by liraglutide. Compared with liraglutide group, treatment with rapamycin, a specific inhibitor of mTOR, compatibly augmented GLP-1 receptor level, inhibited phosphorylation of mTOR/p70S6K and expression of p62 as well as increased level of LC3-II/LC3-I ratio and Beclin-1, suggesting that there is an interaction between GLP-1 and mTOR/p70S6K signaling in the regulation of autophagy. In line with these modifications, treatment with liraglutide and rapamycin significantly reduced perivascular/interstitial fibrosis, and preserved systolic/diastolic function. These results suggest that the inhibitory effects of liraglutide on cardiac fibrosis and dysfunction are potentially mediated by inhibiting mTOR/p70S6K signaling and enhancing autophagy activity.

https://www.scienced...014299920304106

 


Edited by __________________________, 12 July 2020 - 05:33 PM.






0 user(s) are reading this topic

0 members, 0 guests, 0 anonymous users