Hydrogen Sulfide Treatment Improves Post-Infarct Remodeling and Long-Term Cardiac Function in CSE Knockout and...

Area of Science:

• Cardiovascular Research
• Molecular Biology
• Pharmacology

Background:

• Hydrogen sulfide (H2S) is a gaseous signaling molecule produced by cystathionine γ-lyase (CSE) in the cardiovascular system.
• H2S up-regulation and H2S donors show cardioprotective effects against ischemic injury in rodent models.
• Previous studies administered H2S donors concurrently with ischemia, but delayed administration post-myocardial infarction (MI) remains less explored.

Purpose of the Study:

• To evaluate the therapeutic potential of delayed H2S administration in ameliorating cardiac remodeling after MI.
• To compare the efficacy of H2S therapy in wild-type (WT) and CSE gene-deleted (CSE-/-) mice.
• To assess the impact of H2S on cardiac function, hypertrophy, fibrosis, and apoptosis markers post-MI.

Main Methods:

• Myocardial infarction (MI) was induced in WT and CSE-/- mice via coronary artery ligation.
• The H2S donor GYY4137 was administered 2 hours post-MI and daily for 28 days.
• Cardiac function, infarct size, and gene expression related to cardiac remodeling were analyzed in atrial, ventricular, and kidney tissues.

Main Results:

• Delayed administration of GYY4137 post-MI reduced infarct area and restored cardiac function.
• GYY4137 treatment normalized elevated ventricular gene expression associated with cardiac remodeling.
• CSE-/- mice exhibited higher blood pressure and atrial Mir21a expression, but showed similar long-term responses to MI compared to WT mice.

Conclusions:

• The H2S donor GYY4137, when administered after MI onset, effectively preserves cardiac function and protects against adverse cardiac remodeling.
• Endogenous CSE gene deletion does not significantly worsen the long-term cardiac response to MI.
• H2S therapy holds promise for treating post-MI cardiac remodeling, even when initiated after the ischemic event.