Circulating Endothelial-Cell Test May Predict Plaque Rupture

Reed Miller

March 22, 2012

March 21, 2012 (La Jolla, California) — Physicians may soon be able to determine which patients with chest pain are on the brink of an acute MI with a blood test that measures circulating endothelial cells (CEC), a study by researchers at the Scripps Translational Science Institute shows [1].

"We have used a very robust technology to quickly and accurately identify circulating endothelial cells in a STEMI [ST-segment elevation MI] population as compared with healthy controls. [This is a] significant advance beyond the previous trials, in that we used rapid technology to do this," Dr Paddy Barrett (Scripps Translational Science Institute, La Jolla, CA) told heartwire . "[The study results] show that, at a morphological level, these cells are grossly different between the MI group and the healthy control group, as they display vastly different morphological characteristics."

The project at Scripps was launched and led by senior author Dr Eric Topol; Barrett has now taken over the project, trying to apply this knowledge into a point-of-care test for acute MI.

Barrett believes that a commercially available point-of-care blood test based on this CEC signature will be available within about two years. The test will take about 20 to 30 minutes and could be performed on every patient presenting to the emergency department with chest pain. This assay will be used on a peripheral whole-blood sample before coronary angiography, which is important in the STEMI population because a coronary catheter disrupts plaques, leading to false elevations in circulating endothelial-cell count, Barrett explained.

The next step in the development of the point-of-care CEC assay is to characterize the genomic and molecular MI-related features of CECs that can be identified by a rapid test, Barrett said. So far, the results of this work have been "encouraging" and suggest the test will be highly accurate, he said.

Looking for MI's signature in CECs

In a report published online March 21, 2012 in Science Translational Medicine, with first author Dr Samir Damani (Scripps Translational Science Institute), researchers present the results of a study comparing peripheral whole-blood samples from 50 patients with STEMI and samples from 44 healthy control patients. Using the CellSearch rare-cell-isolation platform (Veridex, Huntingdon Valley, PA), Damani et al found that CEC counts were significantly elevated in the MI patients vs controls, with median numbers of 19 vs 4 cells/mL, respectively (p < 0.001). The comparison showed no correlation between CECs and typical markers of myocardial necrosis.

Furthermore, morphological analysis of the microscopy images of CECs showed that the area of CECs in MI patients was 2.5 times that of the healthy patients' CECs and that the CECs' nuclear area was about twice as big in MI patients as in healthy controls. The MI patients' CECs were also much larger than that of age-matched healthy patients and age-matched patients with preexisting peripheral vascular disease. Also, the distribution of CEC images that contained from two to 10 nuclei showed that MI patients were the only subject group to contain more than three nuclei per image, suggesting that multicellular and multinuclear clusters are specific to acute-MI patients.

This is the first study to demonstrate these morphological differences in CECs of patients with and without an MI, he said.

The relationship of elevated CEC amounts to acute MI has been known for over a decade, but the CellSearch technology makes it possible to capture CEC data more quickly, efficiently, and robustly than ever before, Barrett said. "This is moving [this test] much closer to the clinical arena and away from the research arena and targeting the actual atherosclerotic plaque rupture that is the sentinel event of the myocardial infarction, rather than just the downstream effects of [an MI]."

This research is supported by a Clinical and Translational Science Award from the National Institutes of Health and funding from the American Reinvestment and Recovery Act. Topol is an author on a patent associated with this work and editor in chief of . Damani and the other coauthors report no conflicts of interest.