Metabolic reprogramming, oxidative stress, and pulmonary hypertension

Mitochondria are highly dynamic organelles essential for cell metabolism, growth, and function. It is becoming increasingly clear that endothelial cell dysfunction significantly contributes to the pathogenesis and vascular remodeling of various lung diseases, including pulmonary arterial hypertension (PAH), and that mitochondria are at the center of this dysfunction. The more we uncover the role mitochondria play in pulmonary vascular disease, the more apparent it becomes that multiple pathways are involved. To achieve effective treatments, we must understand how these pathways are dysregulated to be able to intervene therapeutically. We know that nitric oxide signaling, glucose metabolism, fatty acid oxidation, and the TCA cycle are abnormal in PAH, along with alterations in the mitochondrial membrane potential, proliferation, and apoptosis. However, these pathways are incompletely characterized in PAH, especially in endothelial cells, highlighting the urgent need for further research. This review summarizes what is currently known about how mitochondrial metabolism facilitates a metabolic shift in endothelial cells that induces vascular remodeling during PAH.

Automated summary

Mitochondria are vital for cell metabolism, growth, and function, and play a central role in endothelial cell dysfunction associated with various lung diseases, including PAH. Multiple pathways, such as nitric oxide signaling, glucose metabolism, fatty acid oxidation, and the TCA cycle, are dysregulated in PAH, leading to alterations in mitochondrial membrane potential, proliferation, and apoptosis. Further research is urgently needed, especially in endothelial cells, to fully characterize these pathways and develop effective treatments for PAH.