The Role of Glutamine and Glutaminase in Pulmonary Hypertension

Abstract

Pulmonary hypertension (PH) refers to a clinical and pathophysiological syndrome in which pulmonary vascular resistance and pulmonary arterial pressure are increased due to structural or functional changes in pulmonary vasculature caused by a variety of etiologies and different pathogenic mechanisms. It is followed by the development of right heart failure and even death. In recent years, most studies have found that PH and cancer shared a complex common pathological metabolic disturbance, such as the shift from oxidative phosphorylation to glycolysis. During the shifting process, there is an upregulation of glutamine decomposition driven by glutaminase. However, the relationship between PH and glutamine hydrolysis, especially by glutaminase is yet unclear. This review aims to explore the special linking among glutamine hydrolysis, glutaminase and PH, so as to provide theoretical basis for clinical precision treatment in PH.

Targeted metabolomics combined with network pharmacology to reveal the protective role of luteolin in pulmonary arterial hypertension

“…31 Furthermore, the changes in metabolites, such as oxaloacetate, N -acetyl- l -ornithine, ornithine, glutamic acid, and butane diacid were in agreement with previous research. 32–35 These findings implied an enormous potential of these metabolites as biomarkers for the diagnosis of PAH. Indeed, luteolin had only a mild effect on these metabolites, which indicated that these pathways might be not involved in this process of luteolin-protected PAH.…”

Role of macrophages in pulmonary arterial hypertension

“…In contrast, the role of glutamine metabolism in the development of PAH, particularly glutaminase (GLS) as the key enzyme that initiates the glutamine hydrolysis pathway, has attracted more and more attention worldwide in recent years ( 104 ). Current studies have demonstrated that pro-inflammatory factors secreted by inflammatory cells can cause extracellular matrix (ECM) remodeling and stiffness, leading to pulmonary sclerosis, which is an important component in the pathogenesis of PAH ( 105 , 106 ).…”

The role of prolactin/vasoinhibins in cardiovascular diseases

“…Endothelial dysfunction is a major player in developing PH, and tremendous evidence provided earlier has demonstrated that PRL/vasoinhibins regulate EC function. 2 , 38 , 46 Additional important factors involved in the pathogenesis on PH include genetic predisposition, 68 , 69 autoimmunity, 65 epigenetic regulation, 70 , 71 inflammation, 72 , 73 metabolic derangement, 74 , 75 and environment insults. 76 , 77 PRL has been shown to stimulate the immune cells, increase the synthesis of immunoglobulins and autoantibodies, and promote aberrant immune responses.…”