News Release

Controlling Collagen Levels May Be Key To Fighting Organ Failure Caused By High Blood Pressure

Peer-Reviewed Publication

American Heart Association

DALLAS, August 11 -- People with high blood pressure have elevated blood levels of collagen, a protein, which may help explain why these individuals are at risk for heart failure as well as kidney and other organ failure, according to a study in today's Circulation: Journal of the American Heart Association.

How high blood pressure contributes to organ failure has not been understood. However, researchers from the University of Navarra School of Medicine in Pamplona, Spain found excess collagen and not enough of the chemical that breaks it down in individuals with high blood pressure. The study also provides a possible reason for the effectiveness of ACE-inhibitor drugs: They can help prevent the build-up of collagen and, in turn, the failure of these organs.

Collagen is a vital "building block" that contributes to the shape and function of the skin, heart, blood vessels and other organs. When synthesis exceeds degradation, there is a net accumulation of collagen that can eventually become fibrosis.

When blood vessels become stiff because of fibrosis, the heart works harder to keep blood flowing through the vessels and blood pressure increases. As fibrosis progresses, cells in the heart and vessels are encased in a "cement-like" collagen mesh. The heart and vessels become stiffer, and their cells no longer can function properly.

"Picture giant mastodons, large, perfectly healthy animals. They are like the enlarged heart muscle cells caused by high blood pressure, who are trapped in tar, not unlike fibrous tissue," says Karl T. Weber, M.D., of the University of Missouri Health Sciences Center. His editorial about the study appears in today's issue of Circulation: Journal of the American Heart Association. "Because of this unfriendly environment, these mastodons are unable to move -- much like heart muscle cells unable to properly contract -- and become vulnerable."

The study's lead author, Javier Diez, M.D., Ph.D., and his colleagues show that this process is reversed by treatment with ACE-inhibitors, drugs that are known to interfere with the body's production of a vessel-constricting chemical called angiotensin. The new study suggests that ACE-inhibitors may have another role in the treatment of high blood pressure.

"The ability of some high blood pressure drugs (like ACE-inhibitors) to protect individuals from organ damage might be partially due to the drug's capacity to stimulate collagen degradation," says Diez.

The researchers also found that people who had enlarged hearts before entering the study had smaller, more normal-sized hearts after treatment with ACE-inhibitors.

Diez's study is the first to measure collagen using blood samples instead of the more invasive and complicated testing of heart tissue samples.

Researchers studied blood samples from 26 people with untreated high blood pressure who received lisinopril, an ACE-inhibitor, and compared their findings to blood samples from a "control" group of 23 people with normal blood pressure who were not given any drugs. Before treatment, the people with high blood pressure had more collagen in their blood and less of the collagen-degrading chemical than the control group. Among the people with high blood pressure were 10 individuals who already had an enlarged heart. They had the highest amount of collagen and the lowest levels of the degrading chemical in their blood samples.

An echocardiogram, or ultrasound of the heart, was used to determine the size of each participant's heart before and after the study period.

After one year of drug therapy, participants with high blood pressure had almost the same levels of collagen and the collagen-degrading chemical as the control group. Also, three of the participants who came into the study with enlarged hearts appeared to have smaller hearts on a follow-up echocardiogram.

Diez says the ability to easily measure collagen levels could lead to drugs that help prevent organ damage in people with high blood pressure. "It is a development which can be anticipated in the immediate future. Nevertheless, we are aware that further studies are necessary to validate the application of such treatment in clinical practice."

Co-authors of the study are Concepcion Laviades, M.D., Ph.D.; Nerea Varo, BSc; Javier Fernandez, DSc, M.D., Ph.D.; Gaspar Mayor, M.D.; Maria J. Gil, DSc; and Ignacio Monreal, DSc, M.D.

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