Carnosic acid protects against mitochondrial dysfunction and ferroptosis in myocardial ischemia/reperfusion injury

Xiu-Qi Wang1, Fa-Jia Hu1, Huang Huang2

  • 1Department of Cardiovascular Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.

Insights

Carnosic acid (CA) protects heart cells from injury caused by blood flow interruption and restoration. It works by reducing cell death and maintaining mitochondrial health, particularly through a mechanism involving Mfn2.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Biochemistry

Background:

  • Myocardial ischemia/reperfusion injury (MIRI) involves complex factors like iron overload, oxidative stress, and inflammation.
  • Understanding MIRI's molecular mechanisms is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying MIRI.
  • To evaluate the cardioprotective effects of carnosic acid (CA) against MIRI.

Main Methods:

  • Established in vivo and in vitro models of MIRI.
  • Assessed cell viability, apoptosis, lactate dehydrogenase activity, and mitochondrial dynamics.
  • Investigated the role of Mfn2 in CA's protective effects using adenoviral vectors.

Main Results:

  • CA pretreatment enhanced cardiomyocyte viability and reduced apoptosis and LDH activity.
  • CA inhibited iron overload and abnormal lipid metabolism in anoxic/reoxygenated cardiomyocytes.
  • CA improved cardiac function, reduced infarct size, and decreased oxidative stress and cardiomyocyte apoptosis in MIRI rats.
  • CA's cardioprotective effects were dependent on Mfn2 expression.

Conclusions:

  • CA protects cardiomyocytes against MIRI by inhibiting ferroptosis.
  • CA maintains mitochondrial dynamic homeostasis via an Mfn2-dependent pathway.
  • CA demonstrates significant therapeutic potential for treating MIRI.

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