Methotrexate Improves Left Ventricle Systolic and Diastolic Function in Induced Takotsubo Myocardiopathy Rats

Area of Science:

• Cardiology
• Pharmacology
• Pathophysiology

Background:

• Takotsubo syndrome (TTS) is a stress-induced cardiomyopathy linked to significant morbidity and mortality.
• Microvascular dysfunction, inflammation, and fibrosis are implicated in TTS pathophysiology.

Purpose of the Study:

• To investigate the therapeutic effects of methotrexate (MTX) on ventricular function in a rat model of Takotsubo syndrome.
• To explore MTX's impact on cardiac remodeling, apoptosis, angiogenesis, and fibrosis in TTS.

Main Methods:

• Wistar male rats were induced with Takotsubo syndrome using isoproterenol (ISO) injections.
• Animals received weekly MTX or saline treatments for 4 weeks, followed by echocardiography, histology, and protein expression analysis.
• Key markers assessed included apoptosis (caspase 3, BAX/Bcl-2), angiogenesis (VEGF), hypoxia (HIF-2α), and fibrosis.

Main Results:

• MTX treatment significantly improved left ventricular systolic and diastolic functions, evidenced by higher ejection fraction and normalized E/A ratio.
• MTX reduced myocardial fibrosis, decreased pro-apoptotic marker expression, and lowered hypoxia markers (HIF-2α).
• Increased angiogenesis was observed in MTX-treated rats, indicated by elevated VEGF levels.

Conclusions:

• Methotrexate treatment enhances cardiac function and mitigates adverse cardiac remodeling in a rat model of Takotsubo syndrome.
• Potential mechanisms include anti-fibrotic and pro-angiogenic effects, alongside reduced apoptosis and hypoxia.
• MTX shows promise as a therapeutic agent for Takotsubo syndrome, meriting further clinical investigation.