Roxadustat Attenuates Adverse Remodeling Following Myocardial Infarction in Mice.

Area of Science:

• Cardiovascular Research
• Molecular Medicine
• Pharmacology

Background:

• The CXCL12/CXCR4/ACKR3 axis and hypoxia-inducible factor-1α (HIF-1α) are crucial for myocardial repair following ischemic events.
• Enhancing HIF-1α upregulation presents a therapeutic strategy for improving cardiac function in ischemic cardiomyopathy.

Purpose of the Study:

• To investigate the effects of roxadustat, a prolyl hydroxylase inhibitor (PHI), on HIF-1α stimulation in the context of myocardial infarction (MI).
• To evaluate roxadustat's impact on cardiac remodeling and function post-MI.
• To assess roxadustat's potential as a treatment for ischemic cardiomyopathy.

Main Methods:

• Mice underwent MI and were treated with roxadustat.
• Analysis included nuclear HIF-1 expression, target gene expression (mRNA/protein), inflammatory cell infiltration, and apoptosis.
• Echocardiography was performed to assess cardiac function and remodeling 28 days post-MI.

Main Results:

• Roxadustat significantly increased nuclear HIF-1 and upregulated key target genes (e.g., CXCL12/CXCR4/ACKR3).
• Treatment promoted M2 macrophage infiltration and showed a trend towards reduced apoptosis.
• Echocardiography revealed preserved ejection fraction and attenuated ventricular dilatation, indicating reduced adverse remodeling.

Conclusions:

• Roxadustat effectively stimulates the HIF-1α pathway in the post-MI heart.
• The drug demonstrates significant cardioprotective effects by mitigating adverse cardiac remodeling.
• Roxadustat is a promising, clinically approved therapeutic option for preserving myocardial function after ischemic injury.