Blood vessels in the lungs have a unique characteristic that sets them apart from blood vessels in other parts of the body. In pulmonary hypertension, only the blood vessels in the lungs become progressively stiffened, leading to chronic lung disease, heart failure, and ultimately, death. Researchers at the University of Pittsburgh, led by Stephen Chan, made a surprising discovery about these blood vessel cells in patients with pulmonary hypertension – they have a voracious appetite for two amino acids, glutamine and serine. This unbalanced diet leads to consequences, as the metabolism of these amino acids drives the progression of pulmonary hypertension.
Amino acids are essential building blocks of proteins, which play a crucial role in building cellular structures, carrying out biological functions, and regulating tissue and organ function. In hypertensive pulmonary blood vessels, the metabolism of glutamine and serine leads to the production of two new amino acids, proline and glycine. These amino acids are primary building blocks of collagen protein, which is essential for the structural framework of our skin, muscles, bones, and connective tissues. The increased levels of proline and glycine in hypertensive pulmonary blood vessel cells result in the overproduction of collagen, leading to vessel stiffening and impaired function, which is a hallmark of pulmonary hypertension.
Through the use of rodent models for the disease, the researchers found that by limiting cellular uptake of glutamine and serine, they could prevent the overproduction of collagen and halt disease progression. Additionally, reducing the dietary intake of foods rich in glutamine and serine also helped decrease collagen overproduction. This new understanding of the role of amino acids in pulmonary hypertension opens up the possibility of using dietary interventions as an effective therapy for the disease, in addition to current medications and transplantation.
For patients with pulmonary hypertension, avoiding glutamine- and serine-rich foods or consuming foods with these amino acids depleted may enhance the effectiveness of current treatments. The researchers have also developed a new diagnostic test for pulmonary hypertension using positron emission tomography (PET) scan technology and a glutamine imaging tracer. This tracer allows doctors to track the hunger of cells for glutamine, which can help in early disease diagnosis, implementation of lifestyle and pharmacological interventions, and monitoring the effectiveness of medications in slowing disease progression.
Overall, the discovery of the role of glutamine and serine metabolism in driving the progression of pulmonary hypertension has provided new insights into the disease and potential avenues for treatment. By targeting the dietary intake of key amino acids, lifestyle interventions may complement current medical therapies in managing pulmonary hypertension. Furthermore, the development of a novel diagnostic test using PET scan technology offers a non-invasive method to monitor the hunger of cells for amino acids and assess disease progression, ultimately improving patient care and outcomes in pulmonary hypertension.
