miR-124/PTBP1/PKM axis modulates pulmonary artery endothelial metabolism in a pulmonary thromboembolism rat model

Cellular metabolism is critical for endothelial cell function. Pulmonary artery endothelial cell (PAEC) dysfunction contributes to the progression from pulmonary embolism (PE) to chronic thromboembolic pulmonary hypertension (CTEPH). The mechanisms of metabolic changes in PAECs during this progression remain unclear. This study aimed to explore the role of the miR-124/PTBP1/PKM signaling axis in endothelial metabolic reprogramming and pulmonary arterial intimal remodeling in pulmonary thromboembolism (PTE).

A PTE rat model was established through repeated autologous thrombus injections into the external jugular veins. The miR-124 levels were restored using a miR-124 mimic, and pathological changes in the pulmonary arteries and thrombi were observed. The expression levels of PTBP1, PKM2, PKM1, MPC1, and MPC2 in the pulmonary arterial intima were assessed using immunohistochemistry, polymerase chain reaction (PCR), and western blotting. Biochemical methods were employed to measure blood lactate levels.

Compared to the normal control group, rats with PTE exhibited increased PTBP1 and PKM2 expression in the pulmonary arterial intima, while miR-124, PKM1, MPC1, and MPC2 expression levels were reduced. Overexpression of miR-124 lowered PTBP1 and PKM2 levels in the intima while elevating PKM1, MPC1, and MPC2 levels, ultimately leading to a reduction in lactic acid production.

In the PTE rat model, elevated lactate levels, decreased miR-124 expression in the pulmonary arterial intima, and disrupted energy metabolism were observed. The miR-124/PTBP1/PKM signaling axis may play a role in the reprogramming of cell metabolism during chronic PTE, ultimately contributing to pulmonary arterial intimal remodeling.