Endothelial Progenitor Cells and Percutaneous Coronary Artery Intervention : Editorial to: "Effect of High Dose Statin Pretreatment on Endothelial Progenitor Cells after Percutaneous Coronary Intervention (HIPOCRATES Study)" by A. Eisen et al.

Abstract

In the HIPOCRATES study Eisen et al. give us important insighths into the effects of statins on endothelial progenitor cells (EPC) levels after percutaneous coronary intervention (PCI) [1]. Pretreatment with high-dose statins given before PCI induces an increase in EPC. In the last decade the understanding of EPC has grown, supporting the important role of these cells for vascular health and adding impetus to the search for ways to upregulate their circulating levels. Although it is clear that the contribution to vascular healing of these circulating progenitors is almost certainly due to their paracrine effects, it is also evident that their function is dependent on both the local microenvironment and a synergy between other populations mobilized in response to the vascular insult. In the mid 1990s Risau et al. [2] described the origins of endothelial cells within the embryonic vasculogenesis, finding that the endothelial cells derive from a putative common mesenchymal precursor for endothelium and hematopoietic cells named the hemangioblast. In 1997 Asahara and colleagues published a landmark paper [3] showing that bone marrowderived CD34+ VEGFR-2+ monocytic cells could be isolated from human blood and grown in culture under conditions that yielded cells with endothelial characteristics indicating the contribution of bone marrow-derived putative EPC to adult neoangiogenesis. Two major cell types may be obtained from peripheral blood mononuclear cells: 1) the early-outgrowth EPC, obtained by culturing isolated mononuclear cells for 4–7 days, and 2) the late-outgrowth EPC, that start proliferating only after 2–3 weeks in culture [4]. The early-outgrowth EPC origin from haematopoietic lineage, have a limited proliferative capacity and, differently from mature endothelial cells, present similar features to monocytes since they express the monocytic marker CD14 and the panleucocytic marker CD45 [5]. The early-outgrowth EPCs may have a role as biomarkers. The late out-growth EPC (also called endothelial colony-forming cells [ECFC]) express the endothelial (KDR, CD146 and VE-cadherin), but not the haematopoietic (CD45 and CD14) markers. The late-outgrowth EPC proliferate can form a vascular network, and are probably more related to replacement of defective endothelial cells and vasculogenesis. Circulating late-outgrowth EPC represent <1 % of circulating EPC and are a smaller part of the CD34-positive bone marrow cells used in clinical trials [6]. The level of circulating EPC is low in normal conditions but it rapidly increases in response to physiological and pathological stimuli, including myocardial and peripheral ischemia [7]. The EPC move from the bone marrow and travel to the sites of new vessel growth in the ischemic tissue (injury site): this process called Bhoming^ [8] includes a coordinated sequence of multi-step adhesive and signaling events, including chemoattraction, adhesion, and migration. Some studies report that the EPC number is C. Briguori Laboratory of Interventional Cardiology, Clinica Mediterranea, Naples, Italy