Cell death in blood vessels may be an early target to prevent coronary disease

In addition, the scientist highlighted the strong parallels existing between the apoptotic microenvironment in cardiovascular disease and those present in the tissues of a few degenerative diseases. In the long run, these data could provide better understanding of other untreatable human pathologies.

The sequence of reactions triggered by apoptosis was presented today, September 19th, at the Fourth Annual Meeting of the European Vascular Genomics Network (EVGN, www.evgn.org), the Network of excellence on cardiovascular disease, which is running in parallel with the 4th European Meeting on Vascular Biology and Medicine (EMVBM).

With more than 400 attendants from all over Europe and representatives from the rest of the world, among whom there are cardiologists, diabetes researchers, hematologists, thrombosis scientists, gene therapists and oncologists, the Bristol Meeting offers a stimulating environment for discussion and future planning.

Apoptosis, the programmed cell death that occurs when a cell has accumulated sufficient DNA damages that it is unable to repair its DNA, is centrally involved in the pathogenesis of a whole range of human illnesses and injury states, and atherosclerosis is no exception. However, until recently, its exact role in this pathology was unclear.

Martin Bennett, a leading cardiologist and atherosclerosis expert, set up a series of targeted experiments aimed at understanding the precise mechanism of action of this, otherwise useful, process.

“We decided – explained Bennett – to elucidate the role that VSMCs death has in the timeline of atherosclerosis progression. Using a mouse model that reproduces the human condition, we induced apoptosis of VSMCs only inside the vessel wall, observing, at first, a clear enlargement of the atherosclerotic plaques that almost doubled their size. This is a bad prognostic factor, as the more they grow the more the plaques become brittle”. That was exactly the second observation made: after the initial growth, the fibrous cap that encloses a typical plaque became thinner, whereas the plaque core increased. “All these signals – points out Bennett – could be useful at the bedside, for a real-time monitoring of atherosclerosis progression”. Not enough, after these first events, the researchers confirmed that the whole region involved in the apoptotic process undergoes calcification. This, in turn, prevents the remodelling of a vessel and, when occurs in a patient, it worsens his or her prognosis.

Furthermore, from Bennett’s investigation emerged striking analogies with two degenerative diseases: Marfan’s syndrome and Hutchinson Gilford Progeria. In both these diseases the tissues look much similar to the one analysed by Bennett in the atherosclerotic settings, with areas of calcifications, and the same kind of infiltrating cells.

“Early as they are, these data rise hope that apoptosis could be targeted at different levels, in order to prevent the cascade of reactions so noxious for the health. And that, possibly, it will help to find novel therapies also for other ailments”.