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Do you have a healthy heart?

Gabriele Trapp
Department of Chemistry
Stanford University
June 2003

What is your risk of having a heart attack? You may soon be able to go to your physician and get a much better answer to this question. My colleagues and I are currently working on a new technique to find 'signal molecules' in your blood that can tell you how high your current risk of getting a heart attack really is.

Heart disease is the number one cause of death in the US. Commonly used risk factors such as high blood pressure or high cholesterol levels cannot explain all cases of heart disease. Therefore, medical doctors and analytical chemists are working together to find new markers. Preliminary studies suggest that it is possible to determine a new risk factor for heart disease based on the ratio of two amino acids found in blood. In the study that we are currently conducting in our analytical chemistry lab we are looking for a possibility to quantify these 'signal molecules'.

Amino acids are very common in the human body; for example, complex proteins are made up from a large number of amino acids that are connected by chemical bonds. Some amino acids possess important functions in our body. Arginine is an amino acid of importance to my research. It can be transformed into another molecule by an enzyme and then affect other body functions such as blood pressure. Another amino acid important in my study is the closely-related methylated arginine, or ADMA, which competes with arginine for the transforming enzyme and blocks it from being effective. This has a negative influence on the blood pressure.

Several studies indicate that there is a strong correlation between the arginine and ADMA levels in blood and the chance of developing heart disease. The ratio of ADMA to arginine depends on personal lifestyle, and therefore changes over time. Being able to analyze the relative amounts of these two compounds is very important. Yet, the concentration in a small blood sample is very low and there are only few techniques that are able to separate and determine these compounds.

The technique I chose to separate the two amino acids is based on a separation of the blood components in a tiny glass capillary, which has an inner diameter the size of a single hair. The instrument that is used to perform the analysis is commercially available and fully automated. The separation itself is achieved by filling the capillary with a salt solution and then applying a very high voltage to the ends of the capillary. When the sample is introduced by dipping the ends of the capillary into a solution containing a very small amount of blood, the amino acids and other components become charged. The speed in which the molecules move inside the capillary depends only on their size and charge. Smaller, highly charged molecules will move faster than larger molecules of a lesser charge This difference in speed separates the different types of molecules from each other. The type of glass capillary that is used, the type of salt and its concentration and also the applied voltage can influence the speed of the molecules. Based on these principles, I developed a method to separate arginine and ADMA in a blood sample.

The detection of the small amounts present in a blood sample is difficult, but can be achieved when these molecules are tagged with a fluorescent dye. In case of arginine and ADMA, I developed a method to completely react these amino acids with a dye. By this labeling, the molecules can then easily be detected in very small quantities as they are emitting light when they pass a laser beam at the end of the capillary.

In order to prove that ADMA and arginine are indeed markers for heart disease, my lab collaborates with a group at the Stanford School of Medicine. Over the course of 10 years, they have collected multiple blood samples as well as the medical history from over 500 patients, with a total of more than 3000 samples. Together we are currently analyzing all samples with the method I developed. Correlation of the analysis of the data with what actually happened to the patients over time will then allow us to proof that the ratio of ADMA and arginine is indeed a good factor for measuring the risk of getting heart disease.

As a result of this study, in the future you and your loved ones will be able to go to your physician, give a few drops of blood and he or she will be able to tell you how high your current risk of getting heart disease is. In case it is elevated, your doctor will then be able to treat you before you even develop symptoms of heart disease.