Professor Hiroaki Shimokawa's research group in the Department of Cardiovascular Medicine, Graduate School of Medicine, Tohoku University, found that AMP-activated protein kinase (AMPK), one of the enzymes of vascular endothelial cells, suppresses the onset of pulmonary hypertension. It also announced that it has revealed for the first time in the world that the diabetes drug metformin may be useful in the treatment of pulmonary hypertension.
When the lumen of blood vessels in the lungs becomes abnormally narrow and blood flow is impaired, blood pressure in the pulmonary arteries rises abnormally.This is pulmonary hypertension, which causes right heart failure because the heart (right ventricle) forces the heart to flow blood into the narrowed pulmonary artery.The average survival time is about 3 years (in the case of untreated adults), and it is difficult to cure the drug, and embryo transfer is indicated in some cases.It is a fatal disease of unknown cause and has been certified as a designated intractable disease.
In this study, we found that serum from patients with pulmonary hypertension directly suppresses AMPK in the pulmonary artery vascular endothelium.In addition, it was found that suppression of AMPK reduces vascular endothelial function and promotes proliferation of pulmonary artery vascular smooth muscle cells, but as a result, the pulmonary artery thickens and pulmonary hypertension becomes severe.In a study using mice, selective deficiency of AMPK in the vascular endothelium resulted in decreased vascular endothelial function, vascular smooth muscle cell proliferation, and inflammatory cell infiltration, indicating a marked exacerbation of pulmonary hypertension.
Furthermore, when metformin, one of the therapeutic agents for diabetes, was administered to mice, AMPK in the pulmonary artery vascular endothelium was activated, showing a remarkable therapeutic effect on pulmonary hypertension.Metformin is a drug currently commonly administered in the medical care of diabetes, and it is expected that the drug may be useful for the treatment of pulmonary hypertension.
