Protein could prevent blocked arteries

The researchers designed a smaller, soluble, form of N-cadherin that could be transported in the blood stream.  They found that soluble cadherin stabilised the plaques, making them less likely to rupture.

Drs Lyon and George said: "This study is the first demonstration that reduction of cell death with soluble N-cadherin can reduce the likelihood of plaque rupture. It highlights soluble N-cadherin as a potential therapeutic for blocked arteries and thereby heart attack and stroke."

The cellular composition of the plaque is an important factor in the likelihood of plaque rupture. There are two main cell types involved - smooth muscle cells, and inflammatory 'bad' white blood cells, called macrophages. Stable plaques contain high numbers of smooth muscle cells while unstable plaques container fewer smooth muscle cells. The smooth muscle cells form a protective cap over the top of the plaque and provide strength to prevent ruptures from occurring.  Smooth muscle cell death, which occurs during unstable plaque development, causes a weaker cap and increases the likelihood of rupture. Death of macrophages leads to the attraction of further inflammatory cells, which increases the incidence of plaque rupture.

The researchers found soluble N-cadherin reduced the death of both smooth muscle cells and macrophages in culture and in a model of atherosclerotic plaque formation. This reduction in cell death protected the plaques from rupture and caused a more stable plaque type; the size of the smooth muscle cell-rich cap was increased and fewer macrophages were present.

Dr George added that: "Further studies are of course essential, and therefore we and our colleagues are performing longer term experiments and attempting to reduce the size of the molecule to make it more suitable for clinical use."