According to the Centers for Disease Control, heart disease is the leading cause of death in the US with a person dying every 36 seconds from the disease. Coronary artery disease (CAD) is the most common type, and millions of patients undergo invasive cardiac catheterizations for diagnostic coronary angiograms. (1)
However, no arterial occlusions are detected in up to 40% of patients tested. Symptoms and traditional risk factors are not sufficiently reliable indicators of the presence of CAD; therefore, improved non-invasive methods to diagnose CAD are sought.
A collaboration of scientists from George Washington University, Washington DC, Ershov Institute of Informatics Systems Novosibirsk, Russia, and Inova Heart and Vascular Institute, Fairfax, VA conducted a study to identify RNA signatures in blood that could lead to the identification of biomarkers of CAD. The study supports the known relationship between the role of regulatory T cell dysfunction and cardiovascular disease.
Whole blood was obtained from patients who were scheduled for coronary catheterization, and mRNA was analyzed by RNAseq to identify CAD-associated transcripts. Patients with CAD were divided into 3 groups: LOW (≤ 20% stenosis), MID (between 20 and 70% stenosis), and HIGH (≥70% stenosis). Comparisons of the mRNA expression pattern were made between patients with and without CAD, and the transcripts associated with CAD were identified. (2)
RNA expression analysis showed lower expression of lymphocyte markers in patients with MID to HIGH CAD. This expression pattern was observed in CD8+ T cell transcripts, but not B-cells or granulocyte-related transcripts. There was also decreased expression of regulatory T cell markers (FoxP3, CD4, CD25, ETS1, and RUNX1), the degrees of which corresponded with LOW, MID, to HIGH CAD.
Reliable blood biomarkers can help reduce the need for invasive testing while still providing useful diagnostic data. The biomarkers can help detect heart disease where the availability of angiography and other imaging technologies are limited.
The researchers noted that using the identified mRNA expression profiles could suggest that a patient is CAD positive when there are atherosclerotic lesions instead. However, this information would still provide valuable diagnostic information, and combining it with non-invasive imaging techniques could improve interpretation.
In addition to the diagnostic value, the observation of regulatory T cell expression profiles may help identify targets for effective therapeutic agents for coronary and other forms of heart disease.
Blood biomarkers could support the assessment of response to currently available therapies as well, especially given the known response of regulatory T cell counts to statin treatments. (3)
The identified expression profiles could bolster early detection of CAD in asymptomatic people who have significant risk factors for the disease, thus reducing the prevalence of CAD and CAD-related deaths.
