HMGB1 Protein May Be Biomarker of Persistent Pulmonary Hypertension of the Newborn, Study Reports

Measuring the levels of an inflammatory protein known as HMGB1 may help diagnose persistent pulmonary hypertension of the newborn (PPHN) and monitor its progression, according to a study in patients and in a rat model.

The research, “High mobility group box 1 protein (HMGB1) as biomarker in hypoxia-induced persistent pulmonary hypertension of the newborn: a clinical and in vivo pilot study,” was published in the International Journal of Medical Sciences.

Asphyxia (oxygen deprivation) during the perinatal period may result in PPHN, characterized by increased blood pressure in the lungs after birth, and damage in the brain and other organs.

Along with inflammatory factors such as TNF-alpha and interleukin (IL)-6, high levels of HMGB1 have been shown in patients with idiopathic pulmonary arterial hypertension (PAH). Likewise, increased HMGB1 amounts have been found in mouse models of chronic hypoxia (reduced oxygen), while the use of antibodies targeting this protein slowed the progression of PAH.

A team from Capital Medical University and the Third Xiangya Hospital of Central South University, both in China, assessed whether similar changes in HMGB1 levels occur in PPHN.

First, they analyzed serum samples from 12 full-term newborns diagnosed with PPHN up to 16 hours after admission. Researchers also used a rat model to characterize the role of HMGB1 in PPHN.

Results showed that serum HMGB1 levels were significantly higher in newborns with PPHN, compared to healthy controls, and markedly reduced upon PPHN resolution (achieved after an average of 75.6 hours).

Similar changes were found in the levels of TNF-alpha and IL-6. The higher the HMGB1 levels, the greater the serum amount of TNF-alpha and IL-6, both at PPHN onset and upon remission.

In rats, the mean pulmonary arterial pressure in the group with PPHN was higher than in the controls. Similar to the findings in patients, serum levels of HMGB1 were higher in the PPHN group than in the control animals, peaking at 24 hours.

One day after inducing PPHN, the pulmonary arteriole wall in the animals was thicker and the lumen (the interior) was narrower than in controls. However, pulmonary arteriole changes were not as severe as irreversible vascular remodeling after three days, the investigators noted.

Apart from the serum, HMGB1 levels also were higher in the lungs of rats with PPHN at different time-points up to day three. The peak also occurred at 24 hours, decreasing thereafter yet still at greater amounts than in the controls.

Overall, “these results indicate that changes in HMGB1 levels are related to the occurrence and development of PPHN,” the scientists wrote. “HMGB1 changes might thus be used as an early indicator to diagnose hypoxia-induced PPHN and evaluate its improvement.”