University of Toronto researchers get to the heart of heart failure

Researchers at the University of Toronto and the University Health Network have identified two genes that play critical roles in heart function - one that contributes to heart failure and one that protects against it.

"This finding is really amazing because it opens up new avenues for the treatment of cardiovascular diseases and heart failure," says Professor Josef Penninger of U of T's medical biophysics and immunology departments and lead author of a study in the June 20 issue of Nature. He and colleague Dr. Peter Backx, a physiology and medicine professor at U of T's Heart & Stroke/Richard Lewar Centre, found that when both genes - angiotensin converting enzyme (ACE) 1 and 2 - are in balance in mice models, the animals developed healthy hearts.

The researchers initially began the study by looking for genes that controlled heart development in flies. Intrigued by finding that the fly's ACE 2 gene is essential in the development of fly hearts, they broadened the study and look for the role of ACE 2 in rats that develop hypertension and cardiovascular disease.

Using genetically-engineered mice, the researchers found that mice carrying the ACE 1 but not ACE 2 gene developed cardiovascular disease and impaired heart function. It is known that ACE 1 serves an important cardiovascular function by generating certain hormones that cause blood vessels to constrict, which helps the body maintain proper blood pressure. The new study by the Toronto team, however, offers a completely new concept for heart function. ACE 1 by-products may regulate blood pressure and control heart function, but if unchecked, they also can contribute to the progression of heart disease, coronary artery disease and heart failure.

"This is the first time that scientists have been able to show that the ACE 1 enzyme is a critical contributor to the inability of the heart to function optimally. Perhaps even more important, we've also shown that the ACE 2 gene plays a hig

Contact: Janet Wong
University of Toronto

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