Transatlantic team probes kidney’s role in hypertension

Two School of Medicine scientists will join leading researchers in Switzerland, France and Mexico in a transatlantic collaboration aimed at pinpointing the kidney’s role in high blood pressure. The new effort, known as the Transatlantic Network on Hypertension-Renal Salt Handling in the Control of Blood Pressure, is supported by a five-year, $6 million grant from the Leducq Foundation, a Paris-based organization that supports international research collaborations in cardiovascular disease.

Hypertension affects more than 1 billion people worldwide and is one of the most important risk factors for cardiovascular diseases such as stroke and heart attack. The exact causes of hypertension remain unknown, but the kidney’s management of salt levels in the body plays a major role.

Leading the team at Yale are Steven C. Hebert, M.D., chair and C.N.H. Long Professor of Cellular and Molecular Physiology, and Richard P. Lifton, M.D., Ph.D., chair and Sterling Professor of Genetics and an investigator in the Howard Hughes Medical Institute.

“Breakthroughs in understanding and treating this complex and often devastating disease will come from collaborations among top scientists from around the world,” Hebert said. “The grant from the Leducq Foundation unites leaders in salt metabolism and hypertension from Europe and North America to understand the role of deranged salt handling by the kidney in causing and maintaining high blood pressure.”

Hebert is the American coordinator of the project. His European counterpart, Bernard C. Rossier, M.D., of the University of Lausanne in Switzerland, will direct pharmacology and toxicology researchers at Lausanne and at Lausanne University Hospital. Also part of the network are researchers from the National Autonomous University of Mexico, under the direction of Gerardo Gamba, M.D., Ph.D., and a team led by Xavier Jeunemaître, M.D., of L’Hôpital Européen Georges-Pompidou and the College de France in Paris.

The transatlantic team will study the metabolism of sodium, potassium and calcium and their influence on blood pressure. They will focus on the ion channels expressed in the kidney and on genetic factors that lead to a sensitivity or resistance to salt-related hypertension, with the goal of finding new therapeutic targets for the disease. In addition, the researchers will integrate their expertise in population genetics and animal models of hypertension, and they will combine approaches from molecular biology, proteomics and physiology.

The Leducq Foundation funding will enable the group to develop a network of Ph.D. and postdoctoral researchers within the participating institutions; to develop a platform for training, videoconferencing and real-time laboratory discussions using the Internet; and to create a centralized database that will allow easy access to shared tools, instruments, materials, and other resources.

Jean and Sylviane Leducq established the Leducq Foundation in 1996 to support cardiovascular disease research. Jean Leducq’s grandparents owned the famed Le Grand Café in Paris, and his childhood meals were served by the family’s cook, the legendary Auguste Escoffier. The Leducqs bequeathed Ehlers Estate, a Napa Valley, Calif., winery they had founded, to the foundation, which receives a portion of the proceeds from sales of Ehlers Estate wine. One of the foundation’s goals is to promote collaboration between researchers in North America and Europe, and in 2004 it began to accept applications for its Transatlantic Networks of Excellence in Cardiovascular Research Program.

“The Leducq program,” Lifton says, “uniquely allows us to bring together a ‘dream team’ of investigators around the world with diverse expertise in physiology, genetics, and clinical investigation to combine forces to tackle this important medical problem.”