Cardiac Diagnostics Active Research - McDevitt Research Labs UT Austin

The McDevitt group efforts are aimed at addressing cardiac disease in a comprehensive way, both in terms of prevention and treatment. Prevention and early detection are indeed the first, and most important, line of defense against this silent but eventually deadly disease.

The success of this approach is contingent on knowledge and complete understanding of the underlying mechanisms that lead to coronary heart disease (CHD). From this perspective, over the last decade, there has been an explosion of information generated on the role of inflammation, endothelial dysfunction and of specific serum biomarkers in the development of atherosclerosis. A large list of relevant cardiac biomarkers has thus been created along with strong evidence that these biomarkers act synergistically to increase an individual's risk for experiencing a heart attack.

The selection of the biomarkers targeted in the McDevitt cardiac program is thus based on the reported association and contribution of these biomarkers to CHD. Each of these biomarkers has been tied in one way or another to CHD in an independent manner, yet it has not been practical to measure all of these elements concurrently in clinical settings.

A rich source of information related to early disease prediction for CAD is expected from the fingerprint response of these serum biomarkers. In this context, we have targeted specific inflammatory biomarkers whose measurement can contribute to the early diagnosis of atherosclerosis, the underlying cause of heart disease. Those include biomarkers C-reactive protein (CRP), interleukin-6 (IL-6), IL-1b, tumor necrosis factor-a (TNF-a), soluble CD40 ligand (sCD40L), tissue factor (TF), matrix metalloproteinase-8 (MMP-8) and osteoprotegerin (OPG) , and blood cells, such as leukocytes, platelets and circulating endothelial cells.

It is interesting that some of the biomarkers that provide insight into the risks for developing heart disease are also relevant to the diagnosis of the actual event of a heart attack. Providing the appropriate treatment(s) to the heart attack victim constitutes the second line of defense against heart disease and relies on a more efficient and accurate diagnosis method.

Both protein and cellular blood tests are obviously needed for cardiac risk assessment and a prompt and accurate diagnosis of a heart attack, as they provide crucial, accurate, minimally invasive diagnosis of the event and subsequently help determine the appropriate treatment to be employed. Often ordered at the same time, these tests have to be conducted on different instruments, each of which may be dedicated to only one type of marker, either a protein or a cell type, but never both. Consequently, this translates into large sample volume requirements and a redundancy of the procedures applied, proportional to the number of analytes to be tested. Furthermore, the relevant instruments designed to perform such measurements are mostly restricted to a laboratory-type of testing and are not amenable for the relevant to heart attack settings such as the in the emergency room or the ambulance.

The McDevitt cardiac project has a strong focus on assay development. Our goal here is to take advantage of the outstanding features of the electronic taste chip (ETC) system to develop superior immunoassays with wider and more sensitive detection capabilities. Each assay is developed first as a single test and optimized to achieve the detection ranges relevant to the reported physiological and pathological levels of each analyte. Once all assays are fully developed, they are combined with the other assays and conditions are adjusted for optimized multiplexed testing. Here all of the selected biomarkers are simultaneously captured on beads, detected and measured in parallel assay steps. Incompatible assay chemistries are separated into specific quadrants on the lab-on-a-chip test structure. Concurrent with the assay development efforts on beads, membrane-based tests for the counting of WBCs, CECs and platelets are established.

It should be emphasized that the McDevitt group has been active in ETC immunoassay development for the past 7 years. During this time, a strong competency has been achieved and protocols established that allow the group to attack assay development efficiently and with confidence. In nearly all of our prior efforts, where acceptable reagents were available, the group has met or exceeded the capacity of established ELISA assays.

Our research is aimed in using the multianalyte testing capacity of our system for the simultaneous measurement of the aforementioned biomarkers for the assessment of cardiac risk and prompt and accurate diagnosis of a heart attack. In addition to saving time, reagents and costs, the inclusion of multiple cardiac factors in one comprehensive test promises to identify unique "signature responses" associated with heart disease to promote a more accurate prediction of cardiac risk.

This strategy involves the development of a dual function biochip with combined bead- and membrane-based platforms that accommodate concurrent tests for protein and cellular cardiac targets, respectively. This dual function biochip is entirely dedicated to the cardiac theme.

In addition, our group is especially interested in applying the ETC technology to study the association between heart disease and the occurrence of periodontal conditions. The positive correlation between serum CRP with both periodontal disease and cardiac disease may indicate that circulating inflammatory molecules contribute to the pathogenesis of both conditions. Undergoing studies in our laboratory are aimed in determining the partitioning of these inflammation markers in the serum and the fluids of the oral cavity to better understand the relationship of these two inflammatory diseases.