Protein behind heart's 'tick-tock' identified

Washington, Dec 3 : A team of American researchers has identified a protein that plays a key role in the daily rise and fall of blood pressure and heart rate, leading to changes in the heart beat.

Researchers at the University of Utah and Salt Lake Veterans Affairs Medical Center say that this protein is called peroxisome proliferator-activated receptor-g (PPARg).

The finding is significant because many cardiovascular events like sudden cardiac death, heart attack, and stroke display daily variations with an increased incidence in the early morning hours.

Since PPARg is best known as the molecular target for a class of widely prescribed and effective diabetes drugs, the findings might also explain why commonly used diabetes drugs come with cardiovascular benefits.

During the study, the researchers examined two strains of mice, each lacking PPARg only in cardiovascular cells.

They found that both knockout strains showed a significant reduction of circadian variations in blood pressure and heart rate.

The mice also showed declines in variation of norepinephrine/epinephrine in their urine-a measure of activity of the sympathetic nervous system, which plays a key role in heart rate and blood pressure.

The animals had impairments in the rhythmicity of the major clock genes, including Bmal1, a transcription factor that controls the activity of other core clock components.

By treating the mice with the diabetes drug rosiglitazone, they were able to increase the activity of Bmal1 in the animals' aortas, the largest artery of the body that issues blood from the heart, and further study showed that the core clock gene is directly controlled by PPARg.

" Our major finding is that PPARg has a circadian function in the vasculature," said Tianxin Yang of the University of Utah and Salt Lake Veterans Affairs Medical Center.

The data also suggest that diabetes drug thiazolidinediones' (TZD) benefits for the cardiovascular system may stem from their ability to restore circadian rhythms.

Indeed, he added, PPARg may have circadian functions in many other metabolic tissues throughout the body.

The study is published in the December issue of the journal Cell Metabolism, a Cell Press publication.

ANI