Paeoniflorin attenuates cuproptosis and ameliorates left ventricular remodeling after AMI in hypobaric hypoxia

Xin Fang1, Yaoxuan Ji2, Shuang Li1

  • 1Department of Radiology, West China Hospital, Sichuan University, No. 37 Guoxue Road, Chengdu, 610041, China.

PubMed

Insights

Paeoniflorin (PF) protects against heart damage after acute myocardial infarction (AMI) in high-altitude conditions. This study shows PF improves heart function by reducing cell death, inflammation, and scarring, offering potential therapeutic benefits.

Area of Science:

  • Cardiovascular Research
  • Altitude Physiology
  • Pharmacology

Background:

  • Left ventricular remodeling post-acute myocardial infarction (AMI) worsens heart failure, particularly at high altitudes.
  • Hypobaric hypoxia presents unique challenges for cardiac recovery after AMI.
  • Paeoniflorin (PF) is a potential therapeutic agent for cardiovascular conditions.

Purpose of the Study:

  • To investigate the cardioprotective effects of Paeoniflorin (PF) on left ventricular remodeling in a rat model of AMI under hypobaric hypoxia.
  • To evaluate the impact of PF on cardiac function and pathological changes following AMI at high altitude.
  • To elucidate the underlying mechanisms of PF's cardioprotective action, including its effects on cuproptosis, oxidative stress, apoptosis, inflammation, and fibrosis.

Main Methods:

  • Establishment of an AMI rat model under hypobaric hypoxia.
  • Administration of Paeoniflorin (PF) for 4 weeks post-AMI.
  • Assessment of left ventricular function using cardiac magnetic resonance imaging.
  • Biochemical analysis of cuproptosis markers (FDX1/DLAT, serum copper, pyruvate), oxidative stress, apoptosis (Bcl-2, Bax), inflammation (NLRP3), and fibrosis.

Main Results:

  • PF significantly improved left ventricular function and attenuated remodeling in rats with AMI under hypobaric hypoxia.
  • PF treatment reduced FDX1/DLAT expression and serum copper levels, while increasing pyruvate.
  • PF effectively mitigated apoptosis, inflammation, and fibrosis by modulating key molecular markers.

Conclusions:

  • Paeoniflorin (PF) demonstrates significant therapeutic potential for managing left ventricular remodeling after AMI at high altitudes.
  • PF exerts its cardioprotective effects by inhibiting cuproptosis, inflammation, apoptosis, and fibrosis.
  • Further research is needed to optimize PF dosage and duration and fully understand its mechanisms of action in hypobaric hypoxia conditions.