A deficiency of the amino acid arginine may contribute to the development of
pulmonary hypertension — a potentially deadly complication — in people with
sickle cell anemia, a new study suggests.
A process called hemolysis, in which red blood cells rupture, is what causes
the arginine deficiency, researchers said.
“Within the red blood cell, there is a high concentration of an
arginine-consuming enzyme called arginase,” said the study’s lead author, Dr.
Claudia Morris, the director of research for the pediatric emergency fellowship
at Children’s Hospital and Research Center in Oakland, Calif.
When arginase is released during hemolysis, explained Morris, that “triggers
a cascade of events that lead to pulmonary hypertension.”
The study findings appear in the July 6 issue of the Journal of the
American Medical Association.
Sickle cell anemia is a disease that causes red blood cells to become
sickle-shaped. This abnormal shape makes blood clots more likely, and when a
blood clot blocks a blood vessel it can cause extreme pain, according to the
National Institutes of Health (NIH). These damaged blood cells are also more
likely to break down prematurely in a process known as hemolysis. Sickle cell
disease strikes African-Americans more frequently than other racial groups.
An estimated one person of every three with sickle cell disease will
eventually develop pulmonary hypertension — high blood pressure in the arteries
of the lungs, Morris said. According to the NIH, pulmonary hypertension causes
the heart to work harder and become enlarged. Eventually, it can lead to heart
failure and death,
“It’s a life-threatening condition, and it’s what many adult sickle cell
patients die from,” she said.
For this study, Morris and her colleagues compared 228 people with sickle
cell anemia — ages 18 to 74 — to 36 healthy individuals.
The researchers measured blood amino acid levels and arginase activity. They
also tested all of the participants with sickle cell disease for pulmonary
hypertension using Doppler echocardiography — ultrasound of the lungs.
The researchers found that activity of the enzyme arginase was significantly
higher in people with sickle cell anemia than in the healthy individuals, and
those participants with pulmonary hypertension had the highest arginase
Arginase consumes an important amino acid, arginine, the researchers
explained. They found that study participants with the lowest amounts of
arginine were also 3.6 times more likely to die than those with the highest
levels of bioavailable arginine.