Early Cardiac Gene Transcript Levels in Peripheral Blood Mononuclear Cells Reflect Severity in Stable Coronary Artery Disease

Introduction: The early cardiac marker genes myocardin, GATA4 and Nkx2.5, play a role in both embryonic cardiovascular development and adult cardiovascular disease. We evaluated transcript levels of myocardin, GATA4 and Nkx2.5 in peripheral blood mononuclear cells (PBMCs) in patients with stable coronary artery disease (CAD) and we examined the relationship between these levels and the severity of the disease, estimated by the number of stenotic vessels involved.Methods: Ninety-eight patients with stable CAD (age 66 +/- 9 years) who underwent coronary angiography participated in the study; 66 healthy individuals (age 58 +/- 13 years) were also included for comparison. Gene transcript levels were determined by quantitative real-time reverse transcription polymerase chain reaction.Results: Patients with 3-vessel CAD had elevated transcript levels of myocardin (median difference 2.7, p=0.001, 95% confidence interval, CI: 1-5.8), GATA4 (median difference 0.3, p=0.015, 95% CI: 0.1-1.9) and Nkx2.5 (median difference 16.1, p<0.001, 95% CI: 4.5-23) compared to healthy controls. Patients with 3-vessel CAD also showed elevated transcript levels of myocardin (median difference 2.3, p=0.001, 95% CI: 0.49-5.5) and Nkx2.5 (median difference 11.8, p<0.001, 95% CI: 1.5-21.5) compared to patients with 1-vessel CAD.Conclusions: Early cardiac marker gene transcript levels are significantly higher in the PBMCs of patients with severe stable CAD than in those of healthy controls, and show alterations in their expression profile according to the disease severity status. Our results indicate for the first time that changes in the early cardiac gene expression in the peripheral blood of stable CAD patients, possibly as a result of alterations in circulating cardiovascular progenitor cells that express these genes, may reflect the level of disease severity.