5-HT2B receptor antagonists inhibit fibrosis and protect from RV heart failure

Area of Science:

• Cardiology
• Pharmacology
• Physiology

Background:

• The serotonin (5-HT) pathway is implicated in pulmonary hypertension (PH), but its role in right ventricular failure (RVF) is not well understood.
• Investigating the effects of serotonin receptor antagonists on RVF is crucial for developing new treatments.

Purpose of the Study:

• To evaluate the impact of Terguride (a 5-HT2A and 5-HT2B receptor antagonist) and SB204741 (a 5-HT2B receptor antagonist) on right heart function and structure in a mouse model of pulmonary artery banding (PAB).

Main Methods:

• Mice underwent PAB, followed by 14-day treatment with Terguride or SB204741.
• Right heart function and remodeling were assessed using right heart catheterization, MRI, and histomorphometry.
• Collagen synthesis in cardiac fibroblasts was measured in vitro.

Main Results:

• Both Terguride and SB204741 treatments led to reduced right ventricular fibrosis and improved cardiac function in mice post-PAB.
• 5-HT2B receptor antagonists inhibited TGF-beta1-induced collagen synthesis in RV cardiac fibroblasts.
• Chronic administration of these antagonists mitigated the development and progression of RVF.

Conclusions:

• 5-HT2B receptor antagonists effectively reduce collagen deposition and inhibit right ventricular fibrosis.
• These antagonists represent a potential novel therapeutic approach for managing pressure overload-induced RVF.
• Targeting the 5-HT2B receptor may offer a new strategy for treating right ventricular failure.