Photo of Huser and Rutledge
Research by Thomas Huser and John Rutledge is paving the road toward early detection of heart disease.

Susie Durant is at risk.

The 67-year-old great-grandmother has high blood pressure, high cholesterol and a family history of heart disease. Plus, she is African-American, an ethnic group prone to cardiovascular problems.

It's not fazing her much. When she learned about her blood pressure, she started exercising. And when she learned about her cholesterol, she changed her diet. Throughout it all, she continued to plan for the future. Currently, she is a full-time accounting student at American River College in Sacramento.

Born in Louisiana and a resident of California since she was a teenager, Durant said she has never experienced any indication of heart trouble, such as chest pain, and didn't even know about her high cholesterol until she had a blood test a couple of years ago.

"I've never had any symptoms," Durant said.

The silent killer

Durant is hardly alone. Cardiovascular disease typically does its damage silently, and despite the best efforts of medical science, heart attacks and strokes remain the number-one and number-three leading killers of Americans today. While American Heart Association estimates show that deaths from cardiovascular disease fell 22.1 percent between 1993 and 2003, the bad news is that cardiovascular disease still claims twice as many lives as all cancers combined.

To reduce the number of deaths from heart disease, UC Davis physicians have teamed up with physicists at the NSF Center for Biophotonics Science and Technology at UC Davis, and at Lawrence Livermore National Laboratory, to discover better ways of monitoring the activity of cholesterol, triglycerides and other lipoprotein components in the blood, which play a key role in atherosclerosis, the hardening of blood vessels due to plaque formation.

"We know some of the first metabolic changes that lead to plaque formation occur in adolescence, yet there are no biological markers that allow physicians to accurately diagnose and prevent the eventual progression of disease at this early stage," said John Rutledge, professor and chief of endocrinology, clinical nutrition and vascular medicine at UC Davis Health System.

Defining laser technology

"Our goal is to use lasers to develop a more sensitive clinical test to identify specific lipoproteins in the blood that lead to first deposits of plaque. Armed with this information, physicians could diagnose patients decades before clinical symptoms develop and begin aggressive intervention to prevent, or even reverse, disease."

One of the major technical challenges has been the inability to visualize and dissect an inherently complex and dynamic process, which involves cells of the blood vessel wall, soluble lipoprotein particles, and cells of the immune system. But a new light-based technology called Laser Tweezer Raman Spectroscopy (LTRS) is allowing UC Davis scientists to characterize and distinguish individual cells and their components more closely and more thoroughly than has been possible using traditional biological methods.Through funding and equipment provided by the Center for Biophotonics, this method was specifically adapted to nondestructively investigate the structure of individual lipoproteins.

Photo of angiogram of the heart
A color-enhanced angiogram of the heart shows a plaque-induced obstruction (top center) in a major artery, which can lead to a heart attack.

Thomas Huser, an associate professor in the Department of Internal Medicine at UC Davis Health System and chief scientist at the Center for Biophotonics, is a specialist in LTRS. He and his team, which includes researchers from Lawrence Livermore and UC Davis, are collaborating with Rutledge to study the many lipoproteins that circulate in the blood to better understand their individual role in the development of atherosclerosis.

"We're using laser light to optically suspend lipoproteins so they can be sorted by their chemical make up," said Huser. "Our ultimate goal is to identify specific lipoproteins in the blood that accurately predict the early onset of heart disease."

For the novel spectroscopy studies, the researchers work with plasma from patient blood samples and analyze a suspension containing lipoproteins in a special laser microscope developed by Huser and colleagues. They specifically measure the amount of light scattered by molecular bonds in a lipoprotein particle — its Raman signal. As each lipoprotein emits a unique signal that reflects its biochemical makeup, the researchers are able to identify, sort and biophysically characterize them.

By evaluating blood samples from patients before and after they eat a meal with known quantities of saturated and unsaturated fats, they also are able to see how fat in the diet altered Raman signals.

"Until now, lipoproteins have only been studied in massive quantities," said Huser. "Standard tests ordered to measure cholesterol levels, for example, are purely bio-chemical. They only measure the proportion of lipoproteins. The ability to distinguish individual lipoprotein chemical signatures and determine which ones have the greatest effects on the blood vessel wall has important research and clinical implications."

More detailed studies will likely give scientists a better idea about how some kinds of lipoproteins, such as low-density lipoproteins, form artery-clogging plaques while other types, such as high-density lipoproteins, seem to prevent them. The eventual goal, Rutledge said, is to be able to stratify people into groups with varying risks of disease.

While the current technology will aid in more detailed studies of lipoproteins, it currently is too slow to perform clinical tests.

"We are working with industry to automate this technique," said Rutledge, who is also co-vice chair for research in internal medicine and holds the Richard A. and Nora Eccles Harrison Endowed Chair for Diabetes Research.

Huser added that the team of researchers intends to study blood samples from patients with cardio-vascular disease using LTRS and compare them to healthy patients to look for other potential biomarkers. This work has already begun, and Huser said he already has seen some promising candidates for new biomarkers.

"We have good evidence," Huser said, "but we need to perform more clinical studies that include a more diverse patient population before we know for sure whether we have found a better predictor of heart disease."