Engineering prof wins NIH grant for research on heart disease

KALAMAZOO, Mich.—A Western Michigan University engineering professor has been awarded a $416,816 grant from the National Institutes of Health to continue his research into understanding the underlying biological mechanisms that lead to heart disease.

Dr. James Springstead, assistant professor of chemical and paper engineering, is the recipient of the unusual NIH grant—the first NIH award ever to WMU's College of Engineering an Applied Sciences. He began studying the science behind what leads to blockage inside arterial walls as a postdoctoral researcher at the University of California at Los Angeles. He earned his doctoral degree in chemical engineering at UCLA in 2008.

How heart disease begins

In the early stages of atherosclerosis, the underlying condition leading to heart attacks and strokes, oxidized LDL—low-density lipoprotein—accumulates inside arterial walls. LDL is known as "the bad cholesterol." Springstead's research is focused on measuring the biological activity of oxidized phospholipids, which have been shown to inflame and eventually form lesions in arterial linings, and more recently, he's also been studying oxidized fatty acids. Springstead is trying to find the mechanism by which oxidized phospholipids initiate the beginning stages of heart disease.

Here's what has been determined so far. LDL particles enter the artery through the blood. An overabundance of LDL particles can lead to them getting trapped in the lining of the artery. The LDL particles then become oxidized, stimulating the endothelial cells in the arterial wall. These endothelial cells recruit immune cells known at monocytes, a type of white blood cell, and remove the oxidized lipids and also can become bound up on the arterial wall.

Several important factors contribute to the risk of heart disease, including lipid profile and genetics, in addition to environmental factors, such as diet and smoking.

"When you're younger and haven't eaten too many Big Macs, the process works," Springstead says. "But if you overload the system, you end up with fatty streaks in the arteries. So what we're trying to do is understand the biological pathways of this process."

Surprising discovery

But Springstead made a surprising discovery. During the synthesis of an important active oxidized phospholipid, PEIPC, he treated the cells in the inner lining of arteries with a fragment of the lipid to test inflammatory signaling. But instead of upregulating inflammatory pathways, he found this oxidized fatty acid strongly inhibited inflammatory pathways. Furthermore, this oxidized phospholipid is likely to exist in our bodies and has potential to be an important anti-inflammatory mediator in the body. The main focus of this new grant is this oxidized fatty acid, EI.

"As an engineer, I like to look at this beginning process," Springstead says. "The take I'd like to go after, is to try to block initial stages so that the body can take care of itself."

Stents can hold open arteries, Springstead says. But since they are a foreign object, they can cause more inflammation. He likes the idea of choking off the beginning stages.

Springstead always liked chemistry and math, so becoming a chemical engineer was a natural fit. He's excited about continuing his research at WMU because of its new master's program in chemical engineering and the opening of the WMU Homer Stryker M.D. School of Medicine. He is scheduled to teach cardiology classes at the medical school this summer. His project is further strengthened by collaborations with Sangderk Lee of the Saha Cardiovascular Research Center of Kentucky, Mete Civelek of the UCLA Atherosclerosis Research Unit, Greg Cavey of the Southwest Michigan Innovation Center, and Walt Shaw of Avanti Polar Lipids.

Springstead has also bought a significant amount of surplus equipment, much of it from pharmaceutical giant Pfizer, refurbished it and added it to his lab to carry out experiments.

"The medical school is already connected with industry and hospitals," he says. "By starting off on the right foot, by starting off with engineering and medicine with a nice bridge between them, I think we can have something really special here and really unique."

Springstead's research ultimately could spark other new and important discoveries.

"There are a lot of different things that could happen," Springstead says. "Hopefully, we could develop or at least be involved in developing the science behind an important drug. Whether this drug would block the immune cell binding to the arterial wall or whether it would be cleaving these oxidized phospholipids, there are a lot of possibilities."

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