Why does your blood clot when it flows through a cut but not when it flows through your blood vessels? What maintains the balance between keeping blood fluid but ready to coagulate when necessary?
Dr Therese Kinsella of University College Dublin is an expert in such matters. A senior lecturer in the department of biochemistry, Dr Kinsella recently received the Royal Irish Academy's Award Medal in Biochemistry, the first woman to receive the award in its 15year history.
Her area of particular interest is vascular haemostasis, the business of keeping blood in the liquid state, she explained. There are control mechanisms that prevent blood from clotting spontaneously and when these go wrong, bad things happen.
"Unwanted blood clotting is a major risk factor for vascular disease," she explained. A whole range of things can occur, including heart attack, stroke, hardening of the arteries, kidney failure, pre-eclampsia and angina. The Irish Heart Foundation part-funds Dr Kinsella's work because of the cardiovascular connection.
Her recent work includes new insights into the complex signalling that goes on inside the cells to maintain balance within the cardiovascular system. In the process her studies have also revealed a previously unknown but essential link between the availability of cholesterol and proper haemostasis.
The balance she describes is between substances that promote clotting and those that inhibit it. The clotting promoter is a hormone called thromboxane and the clotting inhibitor is the hormone prostacyclin.
These communicate with the cells via "surface receptors". Their action is comparable to a key fitting a lock. An element of the hormone matches up perfectly and attaches to its receptor on the cell surface and acts like a light switch, she explained. An inhibitor switches the light off, a promoter switches the light on.
It is essential to understand the biochemistry behind these substances, she said, because it allows us to understand how they contribute to health but also to diseased states. Her interest is increased by the fact that about 40 per cent of premature deaths occurring in Ireland is associated with cardiovascular diseases which disturb haemostasis.
Her detailed biochemical study found humans have not one but two thromboxane receptors. Other species studied including monkeys, bovines and mice were found to have only one.
Although the receptor normally responds to the clotting promoter, thromboxane, it is also influenced by prostacyclin. "We have found that one of the receptors is inhibited by the action of prostacyclin while the second isn't," she explained.
The finding "has important implications" in understanding haemostasis in general. "It tells us key things about the regulation of vascular haemostasis. We are really getting at the control level of vascular haemostasis."
Her new research focus is therefore on the second, non-regulated thromboxane receptor. "We don't know what is regulating it," she said. She is also looking at the implications of its non-regulation.
The findings on the essential service provided by cholesterol - long thought to be a major enemy of the cardiovascular system - are equally startling. Cholesterol is found in every cell in the body but too much of it causes serious problems including hardening of the arteries and a higher risk of heart attack.
Cholesterol, however, is essential for the proper working of prostacyclin, the clotting inhibitor. Drugs and foods that reduce cholesterol have also been shown in her experiments to reduce the effectiveness of prostacyclin. This in effect potentially raises, not reduces, the risk of unwanted clotting.
She has tested a wide range of drugs for their influence on prostacyclin signalling. She has worked out their effects on the hormone at therapeutic levels and will publish her findings next month in the British Journal of Pharmacology.