A new blood-based RNA sequencing method to detect coronary artery disease

Diagnosis of CAD is typically based on coronary angiography, an imaging process used to detect restricted blood flow in the heart’s major arteries. Up to 40% of the 1 million cardiac catheterizations performed in the U.S., however, have a “no blockage” test result, despite clinical indications. To improve diagnostic options, Dr Timothy McCaffery, PhD, Professor of Medicine at the George Washington University (GW) School of Medicine and Health Sciences, used a cutting-edge sequencing method to identify an RNA signature in the whole blood of CAD patients who had received diagnoses via angiographies.

“Using SeqLL’s tSMS platform, our team was able to sequence millions of RNA strands per patient at single molecule resolution. This allowed us to reproducibly identify specific RNA transcripts that were altered in patients with coronary disease,” Dr. McCaffrey said. He added that “cardiologists were able to collect the blood while the patients underwent angiographic imaging of their arteries.”

Between two cohorts, one at GW and one at Inova Health System, Dr. McCaffrey and the research team pinpointed new biomarkers from the identified genes that could lend insight into the cause of CAD. For example, they determined that patients with atherosclerosis had reduced activity of their regulatory T-cells, or suppressor T-cells.

“Accumulating evidence suggests that autoimmunity may play a significant factor in CAD. Based on the gene expression pattern in our studies, it appears as though the patient’s immune system becomes stressed, which causes an inappropriate attack on their own arteries,” Dr. McCaffrey explained. “This immune connection extends to COVID-19 as well, as patients have experienced heart-related issues following their bouts with the virus. Our results outperformed the conventional clinical prediction model for CAD and using this new method, blood tests for diagnosing CAD could transform health care.”

Schematic representation of Treg-related TRACs identified by RNAseq

Fig. 8

The control of FoxP3 mRNA and protein expression is known to be controlled by many factors, including promoter methylation, as well as transcriptional regulation by SMYD3, TCF3/E2A, and IKZF4/Eos. FoxP3, in turn, is itself a transcriptional regulator, in association with cofactors such as TRIM28, IRF4, and others. The FoxP3-sensitive target genes, and other regulators such as AHRR, ICOS, TGF-ß, and mTOR, are then intrinsic components of the transition of Treg progenitor cells to functional Tregs.

According to the Centers for Disease Control and Prevention, CAD impacts over 18% of adults in the United States age 20 and older and over 665,000 deaths from cardiovascular disease occur annually.

Daniel Jones, SeqLL’s CEO, President, & Co-founder, stated, “This publication demonstrates the tSMS platform’s ability to produce accurate molecular profiles and generate novel biological insights. This study represents another step toward providing improved, non-invasive diagnostic options to those suffering from coronary artery disease. We at SeqLL strongly support the application of our tSMS platform to the field of cardiovascular health, especially one that impacts so many Americans daily.”

SourceGlobe Newswire

McCaffrey TA, Toma I, Yang Z, Katz R, Reiner J, Mazhari R, Shah P, Tackett M, Jones D, Jepson T, Falk Z, Wargodsky R, Shtakalo D, Antonets D, Ertle J, Kim JH, Lai Y, Arslan Z, Aledort E, Alfaraidy M, Laurent GS 3rd. (2021) RNA sequencing of blood in coronary artery disease: involvement of regulatory T cell imbalance. BMC Med Genomics 14(1):216. [article]

Leave a Reply

Your email address will not be published. Required fields are marked *


Time limit is exhausted. Please reload CAPTCHA.