Blood vessels in the lungs aren't like the others in the
body. This difference becomes clear in pulmonary
hypertension, in which only the lungs' blood vessels stiffen
progressively, leading to chronic lung disease, heart
failure and death. The underlying reasons for this
organ-specific vessel stiffening remained a mystery until
researchers made a surprising discovery about these blood
vessel cells in patients with pulmonary hypertension.
Researchers found that hypertensive pulmonary blood vessel
cells have a voracious appetite for two amino acids,
glutamine and serine, and as happens with any unbalanced
diet, there are consequences. This metabolism of glutamine
and serine is a key driver of pulmonary hypertension disease
progression. Amino acids are the building blocks of
proteins, which help build cellular structures, carry out
biological functions, and regulate tissue and organ
function. As hypertensive pulmonary blood vessels metabolize
glutamine and serine, they create two new amino acids,
called proline and glycine. Proline and glycine are the
primary building blocks of collagen protein, which makes up
30% of body's total protein and provides a structural
framework for our skin, muscles, bones and connective
tissues. The appetite for glutamine and serine and the
resulting elevated levels of proline and glycine in
hypertensive pulmonary blood vessel cells drive the
overproduction of collagen, which leads to vessel stiffening
and impaired function which is the hallmark feature of
pulmonary hypertension. Using rodent models for the disease,
the researchers saw that drugs that limit cellular uptake of
glutamine and serine deprived hypertensive pulmonary blood
vessels of their craving. In turn, the lack of cellular
glutamine and serine metabolism halted the excess production
of collagen building blocks and collagen production. Knowing
amino acids are most often absorbed through our diets, the
team also discovered that reducing the dietary intake of
glutamine- and serine-rich foods helped reduce collagen
overproduction. For patients with pulmonary hypertension,
avoiding foods rich in serine and glutamine, or eating foods
with these amino acids depleted, might bolster the
effectiveness of current medications. |