Discovery of cellular processes which regulate heart's energy supply may pave way for new cardiac therapies
The heart needs a steady supply of energy to function properly. MUHC researcher Dr. Vincent Giguère and his colleagues recently identified several genetic programs which work together to ensure this energy is available. Dr. Giguère’s findings, published in the May 2007 issue of Cell Metabolism, may suggest new approaches to the management of some forms of heart disease.
“The heart is a pump,” says Dr. Giguère. “It needs energy, and it gets this from different fuels found in the body — glucose or fatty acids — depending on availability. We’ve identified two new receptors that control the whole setup. This is very exciting.”
Dr. Giguère and his fellow researchers discovered that two closely related nuclear receptors known as ERR play an essential role in coordinating the expression of a set of proteins that the heart requires to produce the energy it needs to pump effectively.
“Nuclear receptors receive signals from different parts of the body,” explains Dr. Giguère. “These signals ‘tell’ the cell what action to take by controlling which genetic program will be turned on or off in the cell. Because the ERR and receptors are so important to heart function, drugs that influence their activity might offer a novel approach to managing diseases of the heart muscle.”
The receptors identified by Dr. Giguère and his colleagues had already been linked to the activity of cellular power plants called mitochondria. However, their exact role in supplying energy to the heart muscle had not previously been understood.
Using powerful genomic tools, researchers discovered that the ERR and receptors play a key role in regulating the genes which guide the complex biological processes fuelling the heart. Because of this, the two receptors are essential to heart function.
“The receptors control some 400 genes, and probably more,” Dr. Giguère says. “These genes regulate well-defined energy pathways. Several have also been linked to disorders which affect the heart’s pumping power. This discovery was ‘the cherry on the sundae’ for us.”
If it can be shown that the activity of these two ERR receptors can be safely modulated in the human heart, drugs targeting these receptors may hold promise for novel heart therapies. “There are not many ways to prevent heart failure, but molecules that act on these receptors might be one,” says Dr. Giguère.
This study was funded by the Canadian Institutes for Health Research (CIHR) and Genome Quebec/Canada.
The Research Institute of the McGill University Health Centre (RI MUHC) is a world-renowned biomedical and health care hospital research centre. Located in Montreal, Quebec, the institute is the research arm of the MUHC, a university health centre affiliated with the Faculty of Medicine at McGill University. The institute supports over 500 researchers, nearly 1,000 graduate and post-doctoral students, and operates more than 300 laboratories devoted to a broad spectrum of fundamental and clinical research. The Research Institute operates at the forefront of knowledge, innovation and technology and is inextricably linked to the clinical programs of the MUHC, ensuring that patients benefit directly from the latest research-based knowledge. For further details visit: www.muhc.ca/research.
About the McGill University Health Centre
The McGill University Health Centre (MUHC) is a comprehensive academic health institution with an international reputation for excellence in clinical programs, research and teaching. The MUHC is a merger of five teaching hospitals affiliated with the Faculty of Medicine at McGill University — the Montreal Children's, Montreal General, Royal Victoria, and Montreal Neurological hospitals, as well as the Montreal Chest Institute. Building on the tradition of medical leadership of the founding hospitals, the goal of the MUHC is to provide patient care based on the most advanced knowledge in the health care field, and to contribute to the development of new knowledge.