By the time an average American turns 35, two out of three individuals will have some number of fatty deposits–called atherosclerotic plaques–stuck to the insides of their blood vessels. As they age, if plaques continue to accumulate and grow, one may eventually break free from the vessel lining, travel through the body, and impede blood flow to the heart, causing a heart attack. For more than half of all people with atherosclerosis, the first sign of disease is a heart attack. So what if doctors had a routine blood test–that gave a result in mere minutes–that they could use to screen people for degree of atherosclerosis and heart attack risk? Researchers have developed just such a test, using a microfluidic chip that measures the prevalence of certain immune cells and molecules linked to the buildup of blood vessel plaques. They reported the development and application of the chip this week in a PNAS Early Edition article.
“You can look at a beat-up Chevrolet and say that it’s likely to break down,” says biomedical engineer Scott Simon of the University of California, Davis, an author of the new work. Likewise, you can roughly estimate someone’s risk of a heart attack using outward measures like obesity, blood pressure, cholesterol, and age. “But with this test, we’re opening up the hood, looking inside at the parts, and getting a much better idea what might break down and how soon.”
As atherosclerotic plaques build up in the body, they not only cause blood vessels to narrow, but they affect the entire immune system. The inflammation around plaques acts as a homing signal for immune cells, and signals the immune system to produce new and different types of cells to try to fight the fatty buildup. Among these cells are monocytes, white blood cells that end incorporated into the very plaques that elicit the immune response, helping aid in their growth and worsening disease.
In 2011, Simon and his colleagues reported that one particular molecule on the surface of monocytes became more prevalent after people ate a high-fat meal. And the molecule, CD11c, helped the monocytes better adhere to other cells, including those that line the blood vessels atherosclerotic plaques buildup.
The researchers wondered whether, as atherosclerosis progressed, the number of CD11c on monocytes likewise continuously increased since monocytes were constantly being recruited to plaques. Could levels of CD11c be used as a proxy for how advanced someone’s disease was?
To find out, Simon’s team collected blood from 53 people–some healthy, some with risk factors for atherosclerosis, and others with a recent heart attack. They compared the levels of different types of monocytes, as well as the number of CD11c molecules on the surface of those monocytes. By forcing the blood samples through specially designed microfluidics chips, they could get these measures quickly–monocytes with high levels of CD11c stuck to the chip more avidly. And, indeed, in people with a heart attack, more than twice the number of monocytes adhered to the chip.
“Somebody at low risk of a heart attack turns out to have a certain number of these CD11c receptors on their monocytes,” says Simon. “And someone at a higher risk has a higher number.”
When they compared CD11c to other blood markers known to be associated with heart attacks–creatinine kinase and troponin–the levels were always correlated. As someone’s atherosclerosis worsened, CD11c became more prevalent on monocytes in proportion to disease progression.
“The advantage to this test is that these chips can be designed to cost less than $5 per assay and really be used at the bedside,” says Simon. “It gives doctors a really simple, personalized measure of your inflammatory status.”
Because of its low cost and ease of use, Simon imagines the chips one day being used in a routine way to gauge a patient’s heart attack risk. If the chip informs high levels of CD11c, and therefore progressive atherosclerosis, doctors can intervene more aggressively, with drugs and suggestions for lifestyle changes, to try to prevent a heart attack. Such early detection and intervention may provide a means of avoiding plaque buildup in otherwise healthy subjects, Simon says.