Angiotensin Converting Enzymes and the Healthy Heart

In a study using rat and mouse models for hypertension and heart disease, researchers have found that the genes that code for angiotensin converting enzymes (ACE) 1 and 2 are intimately associated with maintenance of a healthy heart. The study was published in the June 20, 2002, issue of Nature.

Investigators from the University of Toronto (UT, Canada) examined three different rat models of hypertension and found that in all three strains, ACE 2 messenger RNA and protein expression were markedly reduced. Then, 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 was known that ACE 1 serves an important cardiovascular function by generating certain hormones that cause blood vessels to constrict, which helps maintain proper blood pressure. The current study found that unless products of ACE 1 were balanced by those of ACE 2, they could 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 have also shown that the ACE 2 gene plays a highly protective role in heart function by counteracting the negative effects of ACE 1 by-products,” said Professor Josef Penninger, lead author, of UT's medical biophysics and immunology departments.

"Unfortunately, while ACE 1 inhibitors do help slow the progression of heart disease, they are not always effective and their use is often limited by side effects,” said Dr. Peter Backx, a UT professor of medicine who also took part in the study. "But if we understand the connection between peptides and ACE inhibitors, we can begin to tailor the drugs to be much more specific.”

The researchers say the study establishes the fact that ACE 2 plays a fundamental role in the cardiovascular system of rats, mice and flies, which strongly suggests the gene is also an important regulator of cardiovascular function in humans. "The transgenic mouse models created in these studies can now be used to develop new approaches to heart disease therapy and new approaches for genetic screening if people are at risk for heart disease and heart failure,” noted Prof. Penninger.




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