Metabolic reprogramming in pulmonary arterial hypertension

Area of Science:

• Cardiovascular Research
• Metabolic Pathways
• Pulmonary Hypertension Pathogenesis

Background:

• Pulmonary arterial hypertension (PAH) is a severe disorder marked by vascular remodeling and right ventricular dysfunction.
• Metabolic reprogramming is a key pathogenic mechanism in PAH progression.

Purpose of the Study:

• To review metabolic pathways, targets, and therapies in PAH pathogenesis.
• To analyze cell-specific metabolic mechanisms in PAH.

Main Methods:

• Systematic review of metabolic alterations in key cell types involved in PAH.
• Analysis of shared and distinct metabolic hallmarks across pulmonary arterial endothelial cells, smooth muscle cells, fibroblasts, immune cells, and cardiomyocytes.

Main Results:

• Shared metabolic features include enhanced aerobic glycolysis and impaired mitochondrial function.
• Cell-specific mechanisms involve PAEC dysfunction, PASMC switching, PAAFs-mediated fibrosis, RVCM inflexibility, and immune cell polarization.

Conclusions:

• Metabolic reprogramming is central to PAH pathogenesis.
• Cell-specific metabolic regulation is a viable strategy for targeted PAH therapies.
• Targeting metabolism may reverse vascular remodeling and improve right ventricular function.