G‐CSF‐Induced Mobilization of CD34⁺ Progenitor Cells and Proarrhythmic Effects in Patients with Severe Coronary Artery Disease

Abstract

This is the first study showing that mobilization of CD34(+) EPCs is safe in patients with severe CAD. The accompanying leukocytosis did not appear proarrhythmic. Changes in P wave duration might be attributable to G-CSF therapy.

The effects of G-CSF-induced mobilization of progenitor cells are limited by ADMA

“…The reason for these findings is still unclear. A recent study evaluating G-CSF in myocardial infarction did not find evidence for an increase in classic systemic inflammatory markers [32]. Experimental data showed that G-CSF does not increase cardiac homing of progenitor cells [8].…”

“…A second SPECT study was conducted on follow-up as well. Further details regarding patient population and study protocol have been published previously [32].…”

Pharmacologic Targeting of Endothelial Progenitor Cells

“…Several other works, while demonstrating that CSFs potently mobilized EPCs, failed to report significant improvements on the cardiovascular parameters under investigation [195][196][197][198]; specifically, left ventricular ejection fraction (LVEF), infarct size and overall left ventricular recovery did not benefit from G-CSF treatment in patients with acute myocardial infarction after reperfusion. Moreover, some authors argued about possible adverse effects [199,200]. The MAGIC trial is the archetype of the potential double-edged sword of CSFs usage: G-CSF therapy, followed by intracoronary infusion of mobilized cells, improved cardiac function and promoted angiogenesis in patients with myocardial infarction, but was dangerously associated with an increased rate of restenosis [201].…”

Endothelial Progenitor Cells in Diabetic Retinopathy

“…The mechanisms by which EPCs mobilize and specifically home to areas of ischemia are highly complex and incompletely understood. They involve a range of pathways and stimulatory factors such as EPO (52), VEGF (53), and G-CSF (54) but it also appears that signals released from apoptotic endothelial cells are important for EPC recruitment to sites of vascular damage (55). Since the homing process is hypoxia-mediated, it is unsurprising that HIF-1α appears to be crucial for EPC recruitment to sites of vascular insufficiency (56).…”