Blood vessels within the lungs aren’t just like the others within the physique. This distinction turns into clear in pulmonary hypertension, by which solely the lungs’ blood vessels stiffen progressively, resulting in continual lung illness, coronary heart failure and dying. The underlying causes for this organ-specific vessel stiffening remained a thriller till College of Pittsburgh researcher Stephen Chan and colleagues made a stunning discovery about these blood vessel cells in sufferers with pulmonary hypertension — they’re hungry.
Chan, Vitalant Chair in Vascular Drugs and Professor of Drugs within the Division of Cardiology on the College of Pittsburgh, and his staff collaborated with the staff of Thomas Bertero on the Université Côte d’Azur in France. They discovered that hypertensive pulmonary blood vessel cells have a voracious urge for food for 2 amino acids, glutamine and serine, and — as occurs with any unbalanced weight loss program — there are penalties. This metabolism of glutamine and serine is a key driver of pulmonary hypertension illness development.
Amino acids are the constructing blocks of proteins, which assist construct mobile constructions, perform organic capabilities, and regulate tissue and organ perform. As hypertensive pulmonary blood vessels metabolize glutamine and serine, they create two new amino acids, known as proline and glycine. Proline and glycine are the first constructing blocks of collagen protein, which makes up 30% of our physique’s complete protein and offers a structural framework for our pores and skin, muscle tissue, bones and connective tissues. The urge for food for glutamine and serine and the ensuing elevated ranges of proline and glycine in hypertensive pulmonary blood vessel cells drive the overproduction of collagen, which results in vessel stiffening and impaired perform — the hallmark characteristic of pulmonary hypertension.
Utilizing rodent fashions for the illness, the researchers noticed that medicine that restrict mobile uptake of glutamine and serine disadvantaged hypertensive pulmonary blood vessels of their craving. In flip, the shortage of mobile glutamine and serine metabolism halted the surplus manufacturing of collagen constructing blocks and collagen manufacturing. Figuring out amino acids are most frequently absorbed by our diets, the staff additionally found that decreasing the dietary consumption of glutamine- and serine-rich meals helped cut back collagen overproduction.
“For the primary time, now we have a dietary maneuver which will function an efficient remedy for the illness,” says Chan, who additionally directs the Vascular Drugs Institute and Heart for Pulmonary Vascular Biology and Drugs on the College of Pittsburgh College of Drugs and UPMC.
For sufferers with pulmonary hypertension, avoiding meals wealthy in serine and glutamine, or consuming meals with these amino acids depleted, may bolster the effectiveness of present medicines. “It opens up a brand new method that we might deal with this illness, as a result of now — as an alternative of simply counting on medicines and transplantation — there are likely efficient life-style interventions,” says Chan.
Chan’s staff additionally harnessed the attribute urge for food of those cells to create a brand new diagnostic take a look at for pulmonary hypertension utilizing positron emission tomography (PET) scan know-how and a glutamine imaging tracer. The imaging tracer acts like a GPS monitor to trace the place glutamine goes within the physique. Because of this, cells hungry for the amino acid mild up on the PET scan, and the depth of that mild reveals how ravenous cells are for glutamine and the place these cells are within the physique. This screening will allow earlier illness prognosis and implementation of life-style and pharmacological interventions and permit docs to verify the efficacy of medicines in slowing illness development.
