Circadian cycles and cardiovascular disease

Research Summary
By: 
Saurab Faruque
Research Assistant

One-fourth of all deaths in the United States are due to heart disease, making it the leading cause of death for Americans. Disruption of the body’s sleep-wake cycle negatively impacts the cardiovascular system, and may increase one’s risk of heart disease. For example, in a recent study conducted by researchers at Harvard Medical School, only three days of reversed sleep-wake cycles increased blood pressure in healthy adults. Although aging also results in a natural decline of the master clock’s function, the dysfunction can be exacerbated by one’s lifestyle. Night-shift work, frequent jet-lag, eating late at night, caffeine, alcohol, nicotine, fatty foods, and sleep deprivation have all been shown to disrupt the body’s master clock function, and they may increase one’s risk of heart disease. But what’s the causal link between disrupted sleep and heart disease?  A new scientific collaboration is aimed to answer this question.

Scientists recently discovered that stiff blood vessels are a major risk factor for this pervasive disease, which may be because the stiffness impairs blood flow and prevents the heart from getting the oxygen and nutrients it needs.

Dr. Zsolt Bagi, researcher at the Medical College of Georgia, studies collagen in blood vessels. Collagen, a structural protein, provides support and strength to our blood vessels, bone, and skin. Bagi found that having excessive levels of another protein, called ADAM17, accelerates the buildup of collagen. More collagen means that the tissue will be more rigid. Rigid blood vessels are a major risk factor for heart disease, which may be because the stiffness impairs blood flow and prevents the heart from getting the oxygen and nutrients it needs.

Vascular biologist Dr. Dan Rudic studies a different protein, called Bmal1. Bmal1 is a light-sensing protein that controls the body’s master circadian clock. The master clock determines your 24-hour sleep-wake cycle, and previous studies have shown that mice completely lose their normal sleep-wake cycle if Bmal1 is lacking. Rudic also witnessed a similar stiffening of blood vessels in mice with abnormal function of Bmal1

Now, Dr. Rudic and Dr. Bagi are collaborating. They are exploring the relationship between Bmal1 and ADAM17 to determine how the master circadian clock is related to the stiffening of blood vessels and consequently to the risk of heart disease. Bagi claims that they have early evidence in their current study that disrupting the master clock – which can happen from drinking too much coffee or sleep deprivation – results in an abnormal increase in amounts of ADAM17. One of their next steps will be to test the idea that the increase in ADAM17 is caused by a change in Bmal1.

To identify points of intervention and therapy for cardiovascular issues, Bagi and Rudic are working hard to identify how exactly the disruptions in the master clock and in Bmal1 effect ADAM17 and result in stiff blood vessels. But they’re making sure to get enough sleep.