Molecule in Glycolytic Pathway Connected to Possible PAH Treatments

A protein within the glycolytic metabolism pathway, which is key to providing energy for cell processes, is increased in induced animal models of pulmonary arterial hypertension. This finding, reported in the journal Respiratory Research in an article entitled, “Up-regulation of Hexokinase 1 in the Right Ventricle of Monocrotaline Induced Pulmonary Hypertension,” may suggest another intervention for treating pulmonary arterial hypertension.

Along with colleagues at The First Hospital of Jilin, Luoyang Central Hospital, and Fu Wai Hospital, lead author Wei-hua Zhang induced pulmonary hypertension in mice using a subcutaneous injection of monocrotaline. This model is one of two commonly used pulmonary hypertension animal models, as it induces vascular remodeling and thickening of the pulmonary vessels.

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Injected mice developed heart failure, and at times of two, three, and four weeks, right ventricle thickness and hemodynamic parameters were evaluated. In addition to finding an increased pulmonary arterial pressure, right ventricular systolic pressure, and right ventricular thickness within three weeks of injection, Zhang identified an increase in mRNA for hexokinase 1 and lactate dehydrogenase A. Probing further, the increase in mRNA led to an increase in hexokinase 1 protein expression in the right ventricle. These changes were not observed in mice that were injected with saline instead of monocrotaline (and did not have pulmonary hypertension).

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The research group did not identify the reason for hexokinase 1 elevation, but they believe it would be worth exploring in the future, as well as experiments identifying increased hexokinase 1 levels in other models of pulmonary arterial hypertension to ensure this is not a monocrotaline-specific phenomenon. Investigating hexokinase 1 inhibitors are of interest to see if pulmonary pressure can be reduced to treat hypertension.

Another possible application of the study may be a means to detect pulmonary hypertension via biomarkers. It could provide another potential technique to add to the toolbox of non-invasive diagnostic tests and accompany Doppler to detect high pressure in the pulmonary vessels.