Johns Hopkins Researchers Uncover Protein Basis for Accurate Heart Attack Indicators

by Tanya Thomas on Nov 10 2008 4:34 PM

Patients suffering from ischemia- the deficiency of blood flow in an organ or a part of it- are more susceptible to cardiac arrests. Now, Johns Hopkins researchers have discovered a set of five proteins in blood which they hope can help set up a highly accurate early warning test to predict heart attack in such patients.

The team comprising over a dozen scientists revealed that it took them a year to perform the study. They believe that theirs is the largest protein analysis ever done at Hopkins.

According to the researchers, their study was based on 76 arterial blood samples from 19 men and women, which had been taken immediately before and after a period of medically induced ischemia lasting as long as 45 minutes.

They called their method of selecting proteins from tens of thousands present in the blood "a pipeline approach".

"From the start, we knew that we were looking for rare, almost unique biomarkers that bore some direct relationship with ischemia," says study senior investigator Dr. Jennifer Van Eyk, whose first step was to remove from the analysis common blood proteins, such as albumin and globulins.

Presenting their work at the American Heart Association's annual Scientific Sessions in New Orleans on November 9, the researchers said that only five proteins were present in significantly increased amounts after ischemia occurred, with at least a doubling in the blood concentration, compared with those recorded during healthy blood flow.

They said that the five proteins were lumican, semenogelin, angiogenin, extracellular matrix protein, and so-called long palate, lung and nasal epithelium carcinoma-associated protein 1.

While all of them are believed to originate in the heart, they can also be found in other tissues varying from the corneas of the eyes, lumican, to semen.

The researchers also revealed that semenogelin had not been seen in the heart ever before, while others like angiogenin are more predictably found in growing blood vessels and muscle tissue, and are actively involved in tissue repair.

They further said that little was known about the remaining two, which ironically have the longest names: extracellular matrix protein, secreted in a rare inflammatory disease; and long palate, lung and nasal epithelium carcinoma-associated protein 1, thought to play a role in innate immunity.

The Johns Hopkins team believes that the presence of all or even a selected set of these proteins in a simple, rapid blood test could aid emergency paramedics and physicians during the critical 12- to 24-hour window before ischemia causes substantial heart tissue damage or death from heart attack.

"Our results lay the foundation for a first-of-a-kind, early-warning system that could save tens of thousands of people on the brink of a heart attack," says Van Eyk, a professor at the Johns Hopkins University School of Medicine and its Heart and Vascular Institute.

The researchers are currently planning to further analyze the five proteins to map their molecular structures, so that an antibody can be identified to bind to one or several of the proteins, laying the basis for a blood test for ischemia. They will also conduct tests to verify that their study findings also apply to ischemia in stroke.