Low level of protective heart failure protein causes high blood pressure

Washington, May 6 : Lower-than-normal levels of a protein, called S100A1, which appears to have protective and healing effects for failing hearts, may result in high blood pressure, according to researchers at the Center for Translational Medicine at Thomas Jefferson University in Philadelphia.

The researchers, led by Patrick Most, M. D., assistant professor of Medicine at Jefferson Medical College and former postdoctoral fellow Sven Pleger, M. D., came to the conclusion after they discovered lower-than-normal levels of S100A1 in cells that line blood vessel walls in animals with high blood pressure.

When the scientists experimentally lowered the amount of S100A1 protein in the animals’ blood vessels, they could dramatically increase blood pressure.

Preliminary results surprisingly found that S100A1 could also be a therapeutic target for blood pressure treatment.

“S100A1 seems to be a major player in the regulation of blood pressure and vascular function. The mechanisms by which this works is by producing more nitric oxide (NO) in the endothelial cells that line the vessel walls. A lack of NO enables hypertension,” said Dr. Most.

Most indicated that S100A1 is an alternative mechanism for increasing heart function. It directly regulates calcium circulation, which drives the contractions in the heart.

After a decade long research, the researchers have proven that loss of the protein causes diseased hearts to fail and that the protein is a potential target for gene therapy for heart failure.

S100A1 is part of a larger family of proteins called S100, and is primarily found at high levels in muscle, particularly the heart. Falling levels of S100A1 are critical in the loss of heart-pumping strength after a heart attack and play an important role in the progression to heart failure. In fact, an earlier study in 1989 showed that the protein was reduced by as much as 50 percent in patients with heart failure.

In the current study the researchers found in both laboratory experiments and in animal models that blood vessels that lack S100A1 cannot relax as well as normal vessels.

“As a result, S100A1 might not only be a good therapeutic target for heart failure, but for hypertension as well,” said Most.

He said that the researchers plan to continue to investigate animal models of hypertension,

“We will test genetically engineered animals to find out whether or not replacing S100A1 can decrease blood pressure,” he noted.

The findings of the research appear in the journal Circulation Research. (ANI)