Ischemia-specific serum biomarkers identified, may lead to blood test that will predict MI

November 10, 2008

Johns Hopkins researchers have identified five proteins that may serve as an early warning of impending myocardial infarction (MI) in patients presenting to emergency rooms with ischemia symptoms. A blood test to detect all, or a subset of these proteins, could be used by physicians and paramedics in the 12- to 24-hour window before ischemia causes tissue damage or death.

Johns Hopkins researchers have identified five proteins that may serve as an early warning of impending myocardial infarction (MI) in patients presenting to emergency rooms with ischemia symptoms. A blood test to detect all, or a subset of these proteins, could be used by physicians and paramedics in the 12- to 24-hour window before ischemia causes tissue damage or death.

“Our results lay the foundation for a first-of-a-kind early warning system that could save tens of thousands of people,” says Jennifer Van Eyk, PhD, professor, Johns Hopkins University Heart and Vascular Institute, Baltimore. Currently available assays for MI test for cardiac troponin proteins I and T, which are released during an MI after some damage has occurred, provide results too late to take preventive action. However, a positive blood test based on the newly identified proteins would allow time for anticoagulation and cardiac catheterization and angioplasty before cardiac tissue damage occurs.

“People experiencing chest pain too often come to the emergency room with subsequent EKG readings showing no evidence that a heart attack has occurred, but still leaving open the question of whether or not a heart attack is imminent,” Dr. Van Eyk says. Having a test to detect proteins specifically released during ischemia would enable physicians to differentiate between chest pain symptoms due to anxiety or gastrointestinal abnormalities and those related to a potentially life-threatening process.

“From the start, we knew that we were looking for rare, almost unique biomarkers that bore some direct relationship with ischemia,” Dr. Van Eyk explains. Researchers used 76 arterial blood samples from 19 men and women taken immediately before and after medically induced ischemia lasting up to 45 minutes. After removing common blood proteins, in-depth analysis identified only five proteins that were significantly increased after ischemia was induced, with all five being at least doubled in blood concentration compared to levels during healthy blood flow.

The proteins related to ischemia were lumican, semenogelin, angiogenin, extracellular matrix protein, and long palate, lung and nasal epithelium carcinoma-associated protein 1. While now, all five proteins are believed to originate in the heart, semenogelin has never before been seen in heart tissue, angiogenin is more often found in blood vessels and muscle tissue, and lumican is common in the cornea. Extracellular matrix proteins are secreted in the presence of inflammatory disease, and long palate, lung and nasal epithelium carcinoma-associated protein 1 is associated with innate immune function.

Researchers will validate these ischemia-specific biomarkers in a larger study and plan to identify an antibody to one or more of them in an effort to develop a viable blood test, Dr. Van Eyk says.