Research from new Center
of Excellence could add decades to lives by preventing kidney, heart damage
The deadliest thing about sickle cell disease isn’t just the
misshapen red blood cells it produces to cause vascular occlusions. A serious
threat appears to come from oxidative stress, scientists are discovering.
Recent research has revealed that sickle cell disease
changes the way reactive oxygen species (ROS) interact with the system that
regulates blood pressure and fluids in the body, the renin angiotensin system.
Over time, the activity of this harmful molecular pathway gradually destroys
kidney and heart function.
Five divisions at Cincinnati Children’s are now teaming up
to study how to control this process. They will use a five-year, $9.6 million grant
from the National Heart, Lung and Blood Institute (NHLBI) to create the
Cincinnati Center of Excellence in Hemoglobinopathy. It is one of nine
cooperative projects nationwide delving into promising lines of research in
“We found that the same renin angiotensin system that causes
renal damage in diabetes and hypertension also is activated by sickle cell,”
says Punam Malik, MD, a researcher in Experimental Hematology and principal
investigator for the new grant. “More importantly, we found that blocking this
signaling pathway in mouse models prevents organ damage when they are
transplanted with sickle cell disease.”
An interdisciplinary team composed of scientists from the
Heart Institute, the Cancer and Blood Disease Institute, and the Divisions of
Experimental Hematology, Hematology, Radiology and Developmental Biology will
explore how this signaling pathway can be manipulated in mouse models and whether
a similar pathway exists and can be controlled in humans with sickle cell
disease. The team also will explore novel non-invasive imaging tools to detect
the earliest signs of cardiac damage in people with sickle cell disease.