Sodium (±)-5-bromo-2-(α-hydroxypentyl) benzoate ameliorates pressure overload-induced cardiac hypertrophy and dysfunction through inhibiting autophagy.

Abstract

Sodium (±)-5-bromo-2-(a-hydroxypentyl) benzoate (generic name: brozopine, BZP) has been reported to protect against stroke-induced brain injury and was approved for Phase II clinical trials for treatment of stroke-related brain damage by the China Food and Drug Administration (CFDA). However, the role of BZP in cardiac diseases, especially in pressure overload-induced cardiac hypertrophy and heart failure, remains to be investigated. In the present study, angiotensin II stimulation and transverse aortic constriction were employed to induce cardiomyocyte hypertrophy in vitro and in vivo, respectively, prior to the assessment of myocardial cell autophagy. We observed that BZP administration ameliorated cardiomyocyte hypertrophy and excessive autophagic activity. Further results indicated that AMP-activated protein kinase (AMPK)-mediated activation of the mammalian target of rapamycin (mTOR) pathway likely played a role in regulation of autophagy by BZP after Ang II stimulation. The activation of AMPK with metformin reversed the BZP-induced suppression of autophagy. Finally, for the first time, we demonstrated that BZP could protect the heart from pressure overload-induced hypertrophy and dysfunction, and this effect is associated with its inhibition of maladaptive cardiomyocyte autophagy through the AMPK-mTOR signalling pathway. These findings indicated that BZP may serve as a promising compound for treatment of pressure overload-induced cardiac remodelling and heart failure.

• Authors: Bo Wang, Deliang Shen, Junnan Tang, Jing Li, Yue Xiao, Xiuying Chen, Chang Cao, Dongjian Han, Erhe Gao, Wen Zhao, Jinying Zhang, Junbiao Chang
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 23 Issue 9 Pg. 6048-6059 (09 2019) ISSN: 1582-4934 [Electronic] England
• PMID: 31222939 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Chemical References

• Angiotensin II
• Metformin
• mTOR protein, rat
• TOR Serine-Threonine Kinases
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (metabolism)
• Angiotensin II (toxicity)
• Animals
• Autophagy (drug effects)
• Cardiomegaly (chemically induced, drug therapy)
• Cell Line
• Heart Failure (drug therapy)
• Male
• Metformin (pharmacology)
• Mice
• Mice, Inbred C57BL
• Myocytes, Cardiac (pathology)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• TOR Serine-Threonine Kinases (metabolism)
• Ventricular Remodeling (drug effects)