An IRCM researcher pinpoints the cellular mechanism responsible for<br>modulating the permeability of blood vessels

MONTREAL, Aug. 12 /CNW Telbec/ - Dr. Jean-Philippe Gratton, Director of the Endothelial cell biology research unit at the Institut de recherches cliniques de Montréal (IRCM), identifies a new intracellular mechanism responsible for modulating vascular permeability: the nitrosylation of beta-catenin protein by nitric oxide. This scientific breakthrough could have a possible impact on the treatment of cancerous tumours by altering the permeability of the blood vessels irrigating them. Dr. Gratton's team will publish the results of its research tomorrow in the scientific journal Molecular Cell.

The permeability of blood vessels is determined, in part, by the space between endothelial cells, or the cells lining the inside of all blood vessels. Increasing permeability is an essential step in angiogenesis, the process of formation of new blood vessels. Vascular endothelial growth factor (VEGF) is responsible for triggering angiogenesis, and increasing vascular permeability through the activation of the eNOS enzyme, which in turn produces nitric oxide (NO), an intracellular gas.

"We already knew that NO plays a very important role in the modulation of vascular permeability and that it could represent a target for blocking the growth of tumours," explains Dr. Gratton. "However, we ignored how it worked. We have now shown that beta-catenin is the specific protein targeted by nitrosylation - the chemical modification of proteins in endothelial cells by NO."

Nitrosylation of beta-catenin allows endothelial cells to detach from one another, thus increasing vascular permeability. This process could eventually help regenerate damaged arteries after a heart attack. On the contrary, reducing endothelial permeability in cancerous tumours could help prevent the creation of new blood vessels on which they feed, and consequently block their growth. A better understanding of NO's functions could therefore have an important impact on numerous fields of research, as this molecule is involved in many physiological and pathological processes.

"The identification of new cell mechanisms responsible for altering the permeability of blood vessels is a an important step in cancer research," says Dr. Morag Park, Scientific Director of the Canadian Institutes of Health Research's Institute of Cancer Research, "this discovery can potentially have a significant impact on how we treat certain types of tumour growth."

All participants in this study are members of the IRCM. Sébastien Thibeault, doctorate student, and Yohann Rautureau, postdoctoral fellow, are the study's co-authors.

The research conducted by Dr. Gratton and his team were funded by the Canadian Institutes of Health Research (CIHR).

Dr. Gratton's complete article can be found on Molecular Cell's website. (http://www.cell.com/molecular-cell/abstract/S1097-2765(10)00535-6)

About Dr. Jean-Philippe Gratton

Jean-Philippe Gratton is a Doctor in pharmacology, and is Director of the research unit in Biology of endothelial cells at the IRCM. He is also Associate IRCM Research Professor and Associate Researcher in the Department of Medicine at the Université de Montréal. Dr. Gratton is a Canada Research Chairholder in Endothelial Cell Functional Signalling.

In 2003, Dr. Gratton's team demonstrated the effects of a molecule with anti-inflammatory properties, cavtratin, on the development of cancerous tumours. This molecule prevents the production of NO and slows the development of tumours by 50% by reducing the permeability of the blood vessels irrigating them. The discovery offered new therapeutic options for certain types of cancer.

About the Institut de recherches cliniques de Montréal (IRCM)

Founded in 1967, the IRCM (www.ircm.qc.ca) is currently comprised of 37 research units in various fields, namely immunity and viral infections, cardiovascular and metabolic diseases, cancer, neurobiology and development, systems biology and medicinal chemistry, and clinical research and bioethics. It also houses three specialized research clinics, as well as eight core facilities and two research platforms with state-of-the-art equipment. The IRCM employs 450 people and is an independent institution affiliated with the Université de Montréal. The IRCM clinic is associated to the Centre hospitalier de l'Université de Montréal (CHUM). The IRCM also maintains a long-standing association with McGill University.

For further information: or to schedule an interview with Dr. Gratton, please contact: Lucette Thériault, Communications Director, Institut de recherches cliniques de Montréal, 514-987-5535, lucette.thé[email protected]; Julie Langelier, Communications Officer, Institut de recherches cliniques de Montréal, 514-987-5555, [email protected]