Most people have heard of ‘good’ and ‘bad’ cholesterol, and know that ‘bad’ cholesterol is a risk factor in cardiovascular disease. But there is another less-well known risk factor that increases the risk of heart disease in more than 20% of the population, which is genetically determined, doesn’t respond to diet or exercise and for which there is currently no treatment.
Sally McCormick, from the Department of Biochemistry at the University of Otago, and PhD student Monika Sharma, tell Alison Ballance about their research into lipoprotein(a) (pronounced as lipoprotein little a), and how understanding it might lead to the development of new drugs.
AB Tell me about fats in blood.
SM Fats [or lipids] don’t occur freely in the blood. So cholesterol and triacylglycerol, another fat, are packaged into specialised molecules … These molecules are called lipoproteins , and that’s because they’re a complex of the lipids and proteins. The proteins are very important for delivering the fats to various tissues, for example the liver. There are specific receptors – you can think of them as gatekeepers – that lock onto these lipoprotein particles and bring them into the liver.
AB What are the consequences of these fats for heart disease?
SM When you get your lipids levels measured what that’s actually measuring is the fats contained in these lipoproteins. So cholesterol and triacylglycerol that are contained in these specialised particles that are required to keep the fats soluble. There’s one lipoprotein particle in particular, called LDL – that stands for low density lipoprotein – that’s a well-known risk factor for heart disease. If you have high levels of it you’re at a higher risk for developing atherosclerosis and heart disease.
AB If there’s a low density one is there also a high density one?
SM Yes, there is. And it’s opposite. It’s good to have high levels of the HDL – it’s known as good cholesterol and it protects the arteries. There’s also another lipoprotein which is not so commonly measured. It’s very related to the bad cholesterol, and it’s called lipoprotein little a … but it has a different metabolic fate and a different uptake pathway, and that’s what we’re trying to study. Elevated levels of it are a very significant risk for heart disease.
Sally says that once the LDL receptor pathway was discovered it led to the development of statin drugs which are very effective in lowering high levels of LDL. She is hoping that understanding lipoprotein little a might similarly lead to the development of a drug.