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.

Corosolic acid ameliorates cardiac hypertrophy via regulating autophagy

“…More recent reports have overwhelmingly supported that myocardial ALP insufficiency results from chronic pressure overload and contributes to maladaptive cardiac remodeling and heart failure [4,20]. Several studies indicated that increased LC3II expression exists in cardiomyocytes under Ang II stimulation [21], in this condition, reducing LC3II, which presenting reducing the autophagosomes, may play protective role in Ang II-induced injury. We speculated that when there is an ALP insufficiency, reducing the numbers of autophagosomes may be beneficial.…”

Downregulation of miR‐128 Ameliorates Ang II‐Induced Cardiac Remodeling via SIRT1/PIK3R1 Multiple Targets

“…Recent studies have shown that autophagy is able to regulate cardiac oxidative stress, hypertrophy, and apoptosis. Hyperactive or dysfunctional autophagy plays a key role in the transition from stable cardiac hypertrophy to decompensated heart failure [ 19 , 20 ]. Therefore, we investigated the effects of downregulating miR-128 on cardiomyocyte autophagy in vivo and in vitro.…”

ICS II protects against cardiac hypertrophy by regulating metabolic remodelling, not by inhibiting autophagy

“…33 Previous studies indicate that inhibiting excessive cardiac autophagy contributes to the prevention of cardiac hypertrophy. [34][35][36] Other studies show that autophagy is only slightly elevated for several days after TAC surgery and that enhancing autophagic flux can benefit the heart by helping it adapt to long-term pressure stimulation. [37][38][39] Although the role of autophagy is controversial, we found that it was significantly activated in both TAC and Ang II-induced cardiac hypertrophy.…”