TRPM4 Modulates Right Ventricular Remodeling Under Pressure Load Accompanied With Decreased Expression Level

Area of Science:

• Cardiovascular Physiology
• Ion Channel Function
• Cardiac Remodeling

Background:

• Right ventricular (RV) function is critical for patients with conditions like tetralogy of Fallot and pulmonary hypertension.
• RV remodeling can progress from compensated states to heart failure.
• Transient receptor potential melastatin 4 (TRPM4) channels are implicated in cardiac remodeling, particularly in the left ventricle.

Purpose of the Study:

• To investigate the role of TRPM4 in RV contractile function and remodeling.
• To assess TRPM4's involvement in a rat model of RV pressure overload.

Main Methods:

• Utilized monocrotaline (MCT)-induced pressure overload in wild-type and TRPM4-deficient rats.
• Assessed RV function via echocardiography and papillary muscle contractility.
• Evaluated RV hypertrophy and pulmonary arterial remodeling through echocardiography and histology.
• Detected TRPM4 protein expression using Western blot in human and animal samples.

Main Results:

• TRPM4 protein was detected in rat and mouse RV myocardium, and in a human tetralogy of Fallot case.
• Under pressure load, TRPM4-deficient rats exhibited significantly increased RV hypertrophy compared to controls.
• MCT-induced alterations in cardiac contractility and pulmonary arterial remodeling were not affected by TRPM4 deficiency.
• TRPM4 expression was significantly downregulated in the RV of MCT-treated rats.

Conclusions:

• RV pressure overload downregulates TRPM4 expression in the RV.
• Complete TRPM4 deletion exacerbates RV hypertrophy under pressure load.
• TRPM4 modulation presents a potential therapeutic strategy for RV remodeling in pulmonary hypertension.