Circulating Angiogenic Cytokines and Stem Cells in Patients with Severe Chronic Ischemic Heart Disease--indicators of Myocardial Ischemic Burden?

Background: Angiogenic growth factors and stem cell therapies have demonstrated varying results in patients with chronic coronary artery disease. A reason could be that these mechanisms are already up-regulated due to reduced blood supply to the myocardium. The objective of this study was to examine if plasma concentrations of circulating stem cells and angiogenic cytokines in patients with severe stable chronic coronary artery disease were correlated to the clinical severity of the disease.

Methods: Fifty-four patients with severe coronary artery disease and reversible ischemia at stress myocardial perfusion scintigraphy were prospectively included. The severity of the disease was quantified by an exercise tolerance test, Canadian Cardiovascular Society angina classification, and Seattle Angina Pectoris Questionnaire. Fifteen persons without coronary artery disease served as control subjects.

Results: Plasma concentration of VEGF-A, FGF-2, SDF-1, and circulating CD34+ and CD34-/CD45- cells were similar in the two groups, but early stem cell markers (CD105, CD73, CD166) and endothelial markers (CD31, CD144, VEGFR2) were significantly different between patients and control subjects (p<0.005-0.001). Diabetic patients had higher concentration of SDF-1 (2528 vs. 2150 pg/ml, p=0.004). We found significant correlations between both VEGF-A, FGF-2, and CD34+ to disease severity, including degree of reversible ischemia, angina stability score, and exertional dyspnoea.

Conclusions: Plasma concentrations of circulating stem cells and angiogenic cytokines have large inter-individual variations, which probably exclude them from being useful as indicators of myocardial ischemic burden.