Missing or Mutated 'Clock' Gene Elevates Vascular Disease Risk

Researchers at Medical College of Georgia have found that circadian clocks that set the rhythmic motion of our bodies for wakeful days and sleepy nights can also set us up for vascular disease when broken.

During the study, they found that mice with mutated or missing 'clock' genes were prone to thick, inflexible blood vessels with narrow passageways, unhealthy changes typically associated with risk factors such as smoking, high blood pressure and cholesterol.

"Having a bad or broken clock seems to promote vascular disease," said Dr. Daniel Rudic, vascular biologist in the MCG Schools of Medicine and Graduate Studies and the study's corresponding author.

The findings suggest increased disease risk for those with mutated clocks, shift workers whose schedule are routinely in conflict with their natural rhythms, as well as others with poor sleep patterns. They also support the merit of developing time-released meds that are in sync with circadian rhythms.

Inside blood vessels, researchers found that clocks regulate key signaling that enables blood vessel dilation and remodeling.

Mice with missing or mutated clock genes have significantly less AKT, an enzyme that promotes the blood-vessel relaxing molecule nitric oxide, and less of nitric oxide precursor eNOS.

In animal models of vascular disease, the altered or missing clocks dramatically accelerated the unhealthy vascular response. In aged mice, the response is even worse, including a predisposition for developing clots.

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Yet mice with mutated rather than missing clock gene fared much better in normal light-dark cycles than those in constant darkness. It was only in constant darkness that vascular injury occurred.

"The dysfunction is clearly light-cycle dependent, demonstrating these effects are related to circadian rhythm," Dr. Rudic said.

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The study is published in this week's issue of Circulation.

Source-ANI
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