A team of researchers in the Chemistry Department at Texas A&M University and the Cardiology and Pediatrics Department at Scott & White Hospital in Temple have developed an unusual collaboration that links fundamental research in chemistry with the treatment of heart disease.

The Texas A&M group is headed by Ronald D. Macfarlane, professor of chemistry. The Scott & White effort is coordinated by Catherine J. McNeal, a Ph.D. chemist - formerly in the Macfarlane group - now an M.D. on the senior staff in internal medicine and pediatrics.

"I have observed that only half of the patients who come to Scott & White suffering from heart attack have high cholesterol levels," says McNeal. "So there are obviously other factors involved that could be investigated by using recent advances in analytical chemistry, specifically capillary electrophoresis and mass spectrometry."

Over the past 20 years, research on the causes of coronary heart disease has revealed many additional factors that depend on the individual.

"While a population-based screen is effective," says Macfarlane, "we can do better by providing a more comprehensive screen tailored to the individual rather than a population."

This screen, called lipoprotein fingerprinting, provides information on the cardiovascular health of the patient, and is as unique as an individual fingerprint.

"What the doctors want to have is some marker that would tell them beforehand whether a particular therapy is going to be successful or not," says Macfarlane. "With this screen, we can measure about 300 different variables, whereas only three variables are available with a blood screen."

The variables from the lipoprotein fingerprinting are related to the content of blood lipoproteins, which are the principal means of transporting lipids in the blood; the chemical composition in terms of proteins; the presence or absence of certain proteins in the blood, or the presence or absence of mutations of certain key proteins.

"Looking at this fingerprint pattern, the doctor would know what particular therapy is going to be more effective," Macfarlane says.

Three main studies are undertaken at Scott & White Hospital, based on lipoprotein fingerprinting analysis.

Clinton Baisden, head of Cardiothoracic Surgery, is leading a study to use the lipoprotein fingerprinting to predict the success or failure of surgery in the treatment of advanced heart disease.

Veronica Piziak, director of the Lipid Clinic, plans to use lipoprotein fingerprinting in monitoring the effectiveness of lifestyle changes for individuals at high risk for heart disease.

Finally, McNeal is using lipoprotein fingerprinting to study infants from families with histories of premature heart disease.

"These new techniques may help to detect and monitor the progression of heart disease in children," says Macfarlane.

He adds, "We would like to tell kids who already have a family history of premature heart disease, 'Look! You already have fatty streaks.' So the kids could exercise or follow some drug therapy. Then they could come back six months later, and we get their lipoprotein fingerprint again. If we see that fatty streaks are disappearing, we could say to the kids: 'Look! You are making progress.'"

"What is particularly valuable in this collaboration is the close interaction between the physicians and the team," he says. "When an analytical problem in the clinical application is identified, we can use our expertise in analytical chemistry to solve the problem in our research, which is supported by the NIH Heart, Lung & Blood Institute and the Houston-based Welch foundation."

Commenting on the work of Macfarlane and McNeal, Lindley Watson, head of the Department of Cardiology at Scott & White Hospital, says, in a letter addressed to Macfarlane: "In the 20 years I have been with Scott & White, I have never seen a more effective bridge between clinical medicine and basic science research than what Drs. Macfarlane and McNeal have developed."

In another letter, G. Russell Warnick, chief scientific officer at Pacific Biometrics, a Seattle-based organization specializing in research on cardiovascular disease, states, "The lipoprotein fingerprinting concept is a new paradigm in the study and treatment of heart disease for the future."

Contact: Ronald D. Macfarlane, (979) 845 - 2021 or macfarlane@mail.chem.tamu.edu

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