Media Release
April 11 2008
Cholesterol keeps us breathing
Evolutionary
studies into what keeps us breathing led to an exciting breakthrough for
UniSA researchers with the discovery that cholesterol is an essential
ingredient in healthy lung function.
This important discovery could lead to lifesaving solutions for
premature babies with breathing difficulties and even for transplant
surgery.
The research team, led by
Associate Professor Sandra Orgeig from UniSA’s
Sansom Institute,
is one of very few globally undertaking evolutionary research on the
pulmonary surfactant system of the lungs of some unusual mammals and
reptiles.
“The pulmonary surfactant system lines the insides of the lungs and
prevents them from becoming stiff and losing their ability to inflate
and deflate. Surfactant is a complex mixture of lipids (fats) and
proteins that line the alveoli, which are situated at the end of the
bronchioles in alveolar sacks. Inside the alveolar walls is a thin layer
of water-based fluid, which keeps our lungs saturated and humidified and
warmed,” Prof Orgeig said.
“The surfactant forms a lining on top of the water-based fluid in the
alveoli, which stops the alveoli from sticking together as the lungs
inflate and deflate,” she said.
“In premature babies, the surfactant system and the lungs aren’t fully
developed, which results in breathing difficulties. Without surfactant
their lungs are incredibly stiff and the babies aren’t capable of
expanding their lungs, which leads to collapse. To help them breathe the
babies are attached to a ventilator, which forces air into their lungs
and, in severe cases, artificial surfactant is also administered by
being vaporised and inhaled into their lungs.
“Our evolutionary studies show that no matter how simple or complex,
every lung that inflates and deflates has surfactant and there are
differences in its composition,” Prof Orgeig said.
The group’s initial discovery that cholesterol is important in the
surfactant system has led to a resurgence in interest from biomedical
surfactant researchers all over the world on the role of cholesterol in
surfactants and whether it should be incorporated as a component of
artificial surfactants.
“While humans can’t cope with body temperature changes, reptiles and
certain groups of mammals called heterothermic mammals can change their
body temperature. Reptiles might have a body temperature that varies
from 10 degrees in the morning to 40 degrees by mid afternoon,” she
said.
How do reptiles and heterothermic mammals cope with temperature changes?
Cholesterol is the key. When their body temperature drops, the lipids go
solid, like butter hardens in the fridge, and softens at higher
temperatures, or turns to liquid if heated.
“The fact that different fats can exist in different states at the same
temperature reflects their different lipid composition, just like oil,
which exists in liquid form in its coolest state when compared with
butter which, at the same temperature is solid,” Prof Orgeig said.
“Cholesterol is a fluidising lipid that makes solid lipids more fluid
so, when added to surfactant, cholesterol enables the surfactant mixture
to be more fluid at a lower temperature. The cholesterol found in
surfactant is in its simplest form as a pure molecule, unlike plasma
cholesterol, which is packaged with proteins to form HDLs and LDLs.
“We know how important cholesterol is for body temperature changes in
mammals. Now we are investigating this further to see if there is value
in including cholesterol in artificial surfactants for premature babies
or adults with severe respiratory distress.
“Knowing how animals cope with changes in their body temperature could
lead to potential applications for transplant surgery, where the human
body temperature has to be lowered, but not to the same extent as
animals going into torpor or hibernation,” Prof Orgeig said.
“We aim to improve our understanding of the complex interaction between
lipids and proteins in normal, but extreme, conditions first, before we
try to determine how they change in abnormal or disease conditions.
Ultimately, we aim to formulate better artificial surfactants for people
with severe respiratory conditions. Unlike premature babies, where the
breathing function is just delayed, artificial surfactants on the market
don’t help adults with complex respiratory conditions,” she said.
With the help of a new ARC Discovery grant, the group will be
collaborating with researchers in Europe and at UniSA’s
Ian Wark Research Institute
to unravel the complex biophysical and biochemical interactions of the
lipid-protein surfactant mixtures of animals under different
physiological conditions.
Several international researchers are also concentrating their efforts
on understanding the exact function of cholesterol and its interactions
with the other lipids and proteins in surfactant. Without the basic
research on surfactant function in reptiles and heterothermic mammals,
we wouldn’t have known to look to cholesterol as a possible solution for
the development of future generations of artificial surfactants.
Contact for interview
- Prof Sandra Orgeig office (08) 8302 2649 mobile 0410 422 712 email sandra.orgeig@unisa.edu.au
Media contact
- Geraldine Hinter office (08) 8302 0963 mobile 0417 861832 email geraldine.hinter@unisa.edu.au