β-catenin mediates monocrotaline-induced pulmonary hypertension via glycolysis in rats

• Published in: BMC cardiovascular disorders Vol. 24; no. 1; pp. 381 - 14
• Main Authors: Meng, Hui, Deng, Yan, Liao, Juan, Wu, Dan-dan, Li, Li-xiang, Chen, Xing, Lan, Wei‑Fang
• Format: Journal Article
• Language: English
• Published: England BioMed Central 23.07.2024; BMC
• Subjects: Animals; beta Catenin - metabolism; Bone marrow; Cell Movement - drug effects; Cell Proliferation - drug effects; Cytokines; Disease Models, Animal; Enzymes; Glycolysis; Glycolysis - drug effects; Heart; Hemodynamics; Hexokinase; Hypertension; Hypertension, Pulmonary - chemically induced; Hypertension, Pulmonary - metabolism; Hypertension, Pulmonary - physiopathology; Hypertrophy; Hypertrophy, Right Ventricular - chemically induced; Hypertrophy, Right Ventricular - metabolism; Hypertrophy, Right Ventricular - physiopathology; Inflammation; Inflammation Mediators - metabolism; L-Lactate dehydrogenase; Laboratory animals; Lactic acid; Leukocyte migration; Lipopolysaccharides; Lungs; Macrophages; Macrophages - drug effects; Macrophages - metabolism; Male; Metabolism; Monocrotaline; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; Myocytes, Smooth Muscle - pathology; NLRP3 inflammasome; Ostomy; Phosphofructokinase; Pulmonary arteries; Pulmonary Artery - drug effects; Pulmonary Artery - metabolism; Pulmonary Artery - pathology; Pulmonary Artery - physiopathology; Pulmonary hypertension; Pyruvate kinase; Pyruvic acid; Rats; Rats, Sprague-Dawley; Signal Transduction; Smooth muscle; Vascular Remodeling - drug effects; Veins & arteries; β-Catenin; Beijing China; China; Glycolysis; β-catenin; Macrophages; NLRP3 inflammasome; Monocrotaline; Pulmonary hypertension
• ISSN: 1471-2261; 1471-2261
• DOI: 10.1186/s12872-024-04000-z

Metabolic abnormalities and immune inflammation are deeply involved in pulmonary vascular remodelling and the development of pulmonary hypertension (PH). However, the regulatory mechanisms of glycolysis in macrophages are still elusive. Cumulative evidence indicates that β-catenin plays a crucial role in metabolic reprogramming. This study aimed to investigate the effect of β-catenin on macrophage glycolysis in PH. LPS-induced BMDMs were generated via in vitro experiments. A monocrotaline (MCT)-induced PH rat model was established, and the β-catenin inhibitor XAV939 was administered in vivo. The role of β-catenin in glycolysis was analysed. The degree of pulmonary vascular remodelling was measured. β-catenin was significantly increased in both in vitro and in vivo models. In LPS-induced BMDMs, β-catenin increased the levels of hexokinase 2 (HK2), phosphofructokinase (PFK), M2-pyruvate kinase (PKM2), lactate dehydrogenase (LDH), and lactate (LA) and the expression of inflammatory cytokines and promoted PASMC proliferation and migration in vitro. XAV939 decreased the level of glycolysis and downregulated the expression of inflammatory cytokines in vivo. MCT promoted pulmonary arterial structural remodelling and right ventricular hypertrophy, and XAV939 alleviated these changes. Our findings suggest that β-catenin is involved in the development of PH by promoting glycolysis and the inflammatory response in macrophages. Inhibition of β-catenin could improve the progression of PH.