Why High Blood Pressure Leads to Heart Failure for Some, but Not for All

According to an Aug. 9 press release, researchers from the Washington University School of Medicine in St. Louis believe they have discovered why some people with high blood pressure develop heart failure, while others don't. The significance of such a finding will mean new treatment methods for high blood pressure.

Thus far they know that when the heart muscle doesn't maintain its energy supply, heart failure eventually occurs. Chronic high blood pressure makes the heart work harder to pump blood and drains the heart muscle's energy. Using animal experiments, Daniel P. Kelly, M.D., and his colleagues found that a protein called estrogen-related receptor alpha (ERR) assists the heart in maintaining its energy supply.

The research team reported in the July issue of "Cell Metabolism" that mice born without the ERR alpha molecular factor developed symptoms of heart failure when their hearts were forced to pump against high pressure. The hearts of normal mice - those with ERR alpha - took that pressure overload without incident and remained in good health. As a result of these findings, Dr. Kelly and his colleagues believe that heart health depends significantly on ERR alpha.

Dr. Kelly said that "the stress of a cardiac pressure overload asks heart muscle to manufacture more high energy compounds, and without ERR alpha, they can't do it. You could say that in high blood pressure conditions, the heart fails because it becomes energy starved. And if you could feed the heart - by using a drug that enhances ERR, for example - you might enable the heart to better keep pace with its energy requirements."

ERR alpha is found in the nucleus of cells and has the ability to sense how much energy is needed for the heart to function properly. When there's an energy shortage, as occurs when the heart muscle has to work harder, the cell's ERR alpha is activated. In those mice that lacked ERR alpha and were exposed to heart muscle overload, there were signs of early heart failure. In other words, the mouse hearts dilated, but didn't contract effectively, the heart walls thinned, fibrous connective tissue accumulated and some of their heart cells died.

The researchers believe these animal experiments clearly show that the heart's ability to produce energy determines the liklihood of heart failure is likely. Dr. Kelly said that "ERR and some of its partners in the cell are a little like puppeteers controlling the expression of genes for energy production. This research is especially exciting because ERR can be activated with small compounds, making it a good target for drugs."

Certainly there are already treatments available for high blood pressure, but virtually all high blood pressure medications act outside of the heart by dilating the blood vessels to reduce pressure. Other treatments thin the blood. However, with this new information about ERR alpha, the focus will likely shift to address energy production and maintenance.

Source:

Press release, High Blood Pressure, Low Energy - A Recipe for Heart Failure; http://www.newswise.com/articles/view/532366/