The heart of the matter

The winner of a UCD science competition is working to improve heart treatment, writes Dick Ahlstrom

The winner of a UCD science competition is working to improve heart treatment, writes Dick Ahlstrom

Heart disease remains the Republic's biggest killer, with thousands of deaths a year from cardiovascular conditions. Now a researcher at University College Dublin is trying to address this heavy toll by improving one of the most common non-surgical treatments for blocked coronary arteries.

Caroline Kavanagh, a third-year PhD student in UCD's pharmacology department, is chasing a very promising new technique for repairing arteries damaged by the treatment, known as percutaneous transluminal coronary angioplasty, or just angioplasty for short.

Her description of her work last week took first place in the college's Merville Lay Seminars competition. The annual event requires graduate researchers to explain their efforts to a lay audience in ordinary language.

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It is a genuine challenge for participants, who only have 15 minutes to describe cutting-edge research and lose points if they fall back on jargon and complex terminology. And this isn't just a project: the students are involved in real research in areas of importance to the advancement of science and medicine.

Angioplasty is a very common procedure used to open arteries partially blocked by a fatty substance or plaque that builds up on the arterial walls. The condition, commonly referred to as hardening of the arteries, leaves the sufferer at significant risk of heart attack.

Angioplasty surgeons insert special balloons into the blocked artery, inflating them to flatten the plaque and so increase blood flow, explains Kavanagh. Sometimes they also insert a stainless-steel device known as a stent; it remains in the vessel, serving as a permanent scaffold to keep it open, she says.

The procedure initially is very successful, but in a limited number of cases the vessel narrows again with a subsequent build-up of plaque, called restenosis. This most likely occurs, she says, because of vessel damage caused during angioplasty and stenting, which can damage the crucial endothelial cells that line the inside of each vessel.

She is trying to prevent or slow restenosis by speeding repair of the damaged endothelial cells. Her approach, one that is also being pursued by research groups abroad, is to use a coating on the stent that can deliver a growth factor directly to the endothelial cells and promote quick cell recovery.

The coatings, temperature-sensitive polymers, were developed in UCD's chemistry department. "I am actually looking at four coatings that differ in their water-loving and water-hating characteristics," says Kavanagh.

Her work is progressing on several fronts. She is studying the coatings' "biocompatibility" with endothelial cells and blood cells. She is examining how well the coatings can first take up, hold and then slowly release growth factor. She is also looking at whether the released factor is capable of helping the endothelial cells repair themselves.

She already has good results on the biocompatibility question. "The polymers do not cause inflammation in endothelial cells or monocytes [white blood cells\]," she says. Nor do they appear to raise a typical antibody response, which means they have a promising biocompatibility.

She has also shown the coatings perform very well in taking up and holding material. Her initial experiments involved not expensive growth factors but a cheaper protein, bovine serum albumin (BSA).

The coatings attract or repel water on the basis of temperature. One coating readily absorbs BSA below four degrees but "closes down" and repels water above it, she explains. Her experiments confirmed that when closing the coating trapped BSA.

Despite becoming hydrophobic, the coating still managed to release small amounts of the BSA protein over time by diffusion. "We were getting a sustained, constant release over 120 hours," says Kavanagh.

She has also done tests that show endothelial cells will readily grow and spread into areas where the growth factor is available. This happens at concentrations well below the levels being released by her prototype stent coatings.

She acknowledges there is still much to be done on her study, which was funded with grants from the Irish Heart Foundation and Enterprise Ireland. Her next move is to load the stent coatings with real growth factor rather than BSA, to confirm there is no change in performance.