▲Professor Sahmin Lee from the Division of Cardiology at Asan Medical Center is treating a patient with aortic stenosis.

Aortic stenosis, a condition in which the aortic valve becomes increasingly calcified due to aging, can progress to heart failure in severe cases. Until now, the only treatment options were thoracotomy or aortic valve replacement. However, a groundbreaking study has now presented the first potential for medication treatment of aortic stenosis.

A research team led by Professor Sahmin Lee from the Division of Cardiology at Asan Medical Center analyzed the valve tissues of patients with aortic stenosis and discovered mitochondrial dysfunction. For the first time, they identified that supplementation with spermidine can restore mitochondrial function and inhibit aortic valve calcification.

Mitochondria, known as the powerhouse of cells, supply energy to the body. When mitochondrial function declines or becomes damaged, it can lead to various conditions such as aging, diabetes, cardiovascular diseases, and cancer. Spermidine, a naturally occurring compound abundant in foods like natto, cheese, brown rice, mushrooms, broccoli, nuts, and soybeans, is known to enhance mitochondrial function and promote autophagy, a process in which cells remove unnecessary components.

Through electron microscopy analysis of valve tissue from patients with aortic stenosis, the research team confirmed significant mitochondrial damage compared to normal valve tissue. Further quantitative analysis using Mito-Tracker staining revealed that mitochondrial function in aortic stenosis patients was only 17%, significantly lower than 41% in the normal control group.

When the research team administered spermidine to the valve cells of patients with aortic stenosis, the expression of genes related to calcification was reduced by nearly half, while markers of mitochondrial function increased more than threefold. Furthermore, in an aging mouse model, the intake of spermidine-enriched water improved mitochondrial function in heart valve tissue and increased the expression of proteins associated with autophagy. Additionally, the thickness of the valve remained comparable to that of the healthy control group, with fibrosis and calcification progression inhibited by more than 50%.

This study was conducted in collaboration with researchers from Harvard Medical School and Brigham and Women's Hospital. The findings were recently published in ‘JACC: Basic to Translational Science,’ a leading journal in the field of cardiovascular research.