Metabolic reprogramming, oxidative stress, and pulmonary hypertension
Marissa D. Pokharel,
David P. Marciano,
Panfeng Fu,
Maria Clara Franco,
Hoshang Unwalla,
Kim Tieu,
Jeffrey R. Fineman,
Ting Wang,
Stephen M. Black
Affiliations
Marissa D. Pokharel
Center for Translational Science, Florida International University, 11350 SW Village Parkway, Port St. Lucie, FL, 34987-2352, USA; Department of Cellular Biology & Pharmacology, Howard Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA
David P. Marciano
Center for Translational Science, Florida International University, 11350 SW Village Parkway, Port St. Lucie, FL, 34987-2352, USA; Department of Cellular Biology & Pharmacology, Howard Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA
Panfeng Fu
Center for Translational Science, Florida International University, 11350 SW Village Parkway, Port St. Lucie, FL, 34987-2352, USA; Department of Environmental Health Sciences, Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL, 33199, USA
Maria Clara Franco
Center for Translational Science, Florida International University, 11350 SW Village Parkway, Port St. Lucie, FL, 34987-2352, USA; Department of Cellular Biology & Pharmacology, Howard Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA
Hoshang Unwalla
Department of Immunology and Nano-Medicine, Howard Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA
Kim Tieu
Department of Environmental Health Sciences, Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL, 33199, USA
Jeffrey R. Fineman
Department of Pediatrics, The University of California San Francisco, San Francisco, CA, 94143, USA; Cardiovascular Research Institute, The University of California San Francisco, San Francisco, CA, 94143, USA
Ting Wang
Center for Translational Science, Florida International University, 11350 SW Village Parkway, Port St. Lucie, FL, 34987-2352, USA; Department of Environmental Health Sciences, Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL, 33199, USA
Stephen M. Black
Center for Translational Science, Florida International University, 11350 SW Village Parkway, Port St. Lucie, FL, 34987-2352, USA; Department of Cellular Biology & Pharmacology, Howard Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA; Department of Environmental Health Sciences, Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL, 33199, USA; Corresponding author. Florida International University’s Center for Translational Science, 11350 SW Village Parkway, Port St. Lucie, FL, 34987-2352, United States.
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.
