Broiler ascites syndrome (AS), also known as pulmonary hypertension syndrome, is a metabolic disease in fast-growing broilers characterized by hypoxia-induced pulmonary vascular remodeling (PVR), including excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs), vascular wall thickening, and fibrosis. However, the role of pyruvate dehydrogenase kinase 4 (PDK4), a key regulator of glucose metabolism, in this process remains unclear. In this study, blood gas and biochemical analyses revealed hypoxemia and acidosis in AS broilers. Histological and molecular assays demonstrated increased pulmonary arterial wall thickness, enhanced PASMCs proliferation, and reduced apoptosis. Transcriptomic and protein analyses showed that PDK4 was significantly upregulated, along with activation of glycolysis and pyruvate metabolism pathways. In vitro, hypoxia (3% O₂, 48 h) promoted PASMCs proliferation, inhibited apoptosis, enhanced glycolysis, and increased lactate production, accompanied by elevated PDK4 expression. PDK4 overexpression reproduced these effects, whereas inhibition by dichloroacetate (DCA) reversed them. Furthermore, lactate treatment promoted PASMCs proliferation and G1/S cell cycle transition. These results indicate that PDK4 drives glycolysis and promotes PASMCs proliferation via lactate‑induced cell cycle progression, thereby participating in PVR in AS broilers.

To Cite This Article: Wu P, Li Y, Chen B, Liu C, Tareen MI, Huang X, Fei L, Tang Z, Wang Y and Li Y, 2026. PDK4 enhanced glycolysis to drive pulmonary vascular remodeling in broiler ascitic syndrome. Pak Vet J, 46(6): 1545-1556. http://dx.doi.org/10.29261/pakvetj/2026.146