The role of macrophages in right ventricular remodeling in experimental pulmonary hypertension

Area of Science:

• Cardiovascular Biology
• Immunology
• Pulmonary Hypertension Research

Background:

• Right ventricular (RV) failure is a major cause of mortality in pulmonary hypertension (PH).
• The precise mechanisms driving RV failure in PH remain incompletely understood.
• Macrophages are increasingly recognized as key players in cardiovascular disease pathogenesis.

Purpose of the Study:

• To investigate the role of cardiac macrophages in the RV response to pulmonary hypertension.
• To determine if macrophage subpopulations in the RV change during PH.
• To elucidate the impact of macrophage depletion on RV remodeling and function in experimental PH.

Main Methods:

• Induction of pulmonary hypertension in mice (hypoxia, Schistosoma mansoni) and rats (SU5416-hypoxia).
• Quantification of cardiac macrophages using flow cytometry and parabiosis models.
• Macrophage depletion in rats using clodronate liposomes.
• Assessment of RV extracellular matrix, vasculature, and function.

Main Results:

• While overall macrophage numbers didn't change in hypoxia-exposed mice, specific subpopulations increased.
• Parabiosis revealed circulating-derived RV macrophages, with one subpopulation significantly expanding under PH stimuli.
• Macrophage depletion in SU-Hx rats altered RV extracellular matrix composition without affecting vasculature, correlating with improved RV function.

Conclusions:

• RV macrophage populations expand and contribute to RV remodeling in pulmonary hypertension.
• These macrophages play a role in regulating the RV extracellular matrix.
• Targeting RV macrophages may offer a therapeutic strategy for pulmonary hypertension-associated RV failure.