doi: 10.1161/CIRCRESAHA.108.175638
© 2008 American Heart Association, Inc.
Editorials |
PI3K
Helps an SDF Seeking Home ... for EPCs
From Inserm U689, Centre de Recherche Cardiovasculaire, Hôpital Lariboisière, 41, Bd de la Chapelle, 75010 Paris, France.
Correspondence to Ziad Mallat, Inserm U689, Centre de Recherche Cardiovasculaire, Hôpital Lariboisière, 41, Bd de la Chapelle, 75010 Paris, France. E-mail ziad.mallat@inserm.fr
See related article, pages 942–949
Key Words: adhesion molecules • angiogenesis • pressure overload • signaling pathways
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
It is increasingly recognized that the quality of tissue repair following an ischemic insult is highly influenced by the phenotype and plasticity of newly recruited blood-borne cells. The latter are capable of switching the tissue response to injury toward either a pathological remodeling, leading progressively to organ failure or to a repair process that preserves and restores tissue function. Thus, identification of the critical pathophysiological pathways that govern mobilization, recruitment, and function of these blood-borne elements is of utmost importance to our understanding of the tissue repair process. Since the first isolation of blood-borne endothelial progenitor cells (EPCs),1 an important body of evidence has been presented indicating that EPCs form a functionally important population endowed with neovascularization promoting capacity. Whatever the mechanisms operated by EPCs to enhance neovascularization, through paracrine effects and/or direct incorporation into vascular beds, their preferential recruitment and homing into the ischemic sites appears to be critical for this function.
Recruitment of EPCs into injured tissues involves an interplay among chemokines/chemokine receptors, integrins, and adhesion molecules, leading to a multistep cascade of events from rolling and adhesion to transendothelial migration and incorporation into sites of neovascularization.2–4 The chemokine stromal cell–derived factor (SDF)-1
, also called CXCL12, is a powerful chemoattractant for human and murine primitive hematopoietic cells.5,6 SDF-1 signals through its single high-affinity 7-transmembrane pertussis toxin-sensitive G protein–coupled receptor, CXCR4. The signal transduction pathways initiated by the binding to CXCR4 are critical to the ability of bone marrow–derived progenitors and EPCs to migrate along an SDF-1 gradient,
Related Article:
Is Integral to Homing Functions of Progenitor Cells
Circ. Res. 2008 102: 942-949.