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Media Release

April 11 2008

Cholesterol keeps us breathing

Associate Professor Sandra Orgeig and Alice the bearded dragonEvolutionary 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.

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