madman
Super Moderator
Summary: Pulmonary hypertension (PH) is a severe and progressive disease characterized by increased pulmonary vascular resistance leading to right heart failure and death. In PH, the cellular metabolisms including those of the three major nutrients (carbohydrate, lipid, and protein) are aberrant in pulmonary vascular cells. Glucose uptake, glycolysis, insulin resistance, sphingolipid S1P, PGE2, TXA2, leukotrienes, and glutaminolysis are upregulated, and phospholipid-prostacyclin and L-arginine-nitric oxide pathway are compromised in lung vascular cells. Fatty acid metabolism is disordered in lung endothelial cells and smooth muscle cells. These molecular mechanisms are integrated to promote PH-specific abnormal vascular cell proliferation and vascular remodeling. This review summarizes the recent advances in the metabolic reprogramming of glucose, fatty acid, and amino acid metabolism in pulmonary vascular remodeling in PH and the mechanisms for how these alterations affect vascular cell fate and impact the course of PH.
9 CONCLUSION
In PH, the cellular metabolisms including those of the three major nutrients (carbohydrate, lipid, and protein) are aberrant in pulmonary vascular cells (table 1). Glucose uptake, glycolysis, IR, sphingolipid S1P, PGE2, TXA2, leukotrienes, and glutaminolysis are upregulated, and phospholipid-prostacyclin and L-arginine-NO pathway are compromised in lung vascular cells. Fatty acid metabolism is disordered in lung endothelial cells and smooth muscle cells. These molecular mechanisms are integrated to promote PH-specific abnormal vascular cell proliferation and remodeling. Although pharmacotherapy such as endothelin-1 receptor antagonists, PDE5 inhibitors, and prostacyclin analogs have been developed, targeting these aberrant metabolic pathways will open new venues to novel PH therapies.
9 CONCLUSION
In PH, the cellular metabolisms including those of the three major nutrients (carbohydrate, lipid, and protein) are aberrant in pulmonary vascular cells (table 1). Glucose uptake, glycolysis, IR, sphingolipid S1P, PGE2, TXA2, leukotrienes, and glutaminolysis are upregulated, and phospholipid-prostacyclin and L-arginine-NO pathway are compromised in lung vascular cells. Fatty acid metabolism is disordered in lung endothelial cells and smooth muscle cells. These molecular mechanisms are integrated to promote PH-specific abnormal vascular cell proliferation and remodeling. Although pharmacotherapy such as endothelin-1 receptor antagonists, PDE5 inhibitors, and prostacyclin analogs have been developed, targeting these aberrant metabolic pathways will open new venues to novel PH therapies.
