Vascular Metabolic Mechanisms of Pulmonary Hypertension

Abstract

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.

Keywords

pulmonary hypertension / metabolism / vascular remodeling / proliferation

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