Vascular Trauma Induces Rapid but Transient Mobilization of VEGFR2+AC133+ Endothelial Precursor Cells

• Published in: Circulation research Vol. 88; no. 2; pp. 167 - 174
• Main Authors: Gill, Muhammad, Dias, Sergio, Hattori, Koichi, Rivera, Mary Lee, Hicklin, Daniel, Witte, Larry, Girardi, Leonard, Yurt, Roger, Himel, Harvey, Rafii, Shahin
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 02.02.2001; Lippincott; Lippincott Williams & Wilkins Ovid Technologies
• Subjects: AC133 Antigen; Animals; Antigens, CD; Biological and medical sciences; Blood Vessels - metabolism; Burns; Burns - blood; Cadherins - genetics; Cadherins - metabolism; Cell Count; Cells, Cultured; Colony-Forming Units Assay; Coronary Artery Bypass; Endothelial Growth Factors - blood; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Flow Cytometry; Glycoproteins - metabolism; Humans; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - metabolism; Lewis X Antigen - metabolism; Lymphokines - blood; Macrophage-1 Antigen - metabolism; Medical sciences; Mice; Peptides - metabolism; Receptor Protein-Tyrosine Kinases - genetics; Receptor Protein-Tyrosine Kinases - metabolism; Receptors, Growth Factor - genetics; Receptors, Growth Factor - metabolism; Receptors, Vascular Endothelial Growth Factor; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Stem Cells - cytology; Stem Cells - metabolism; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the heart; Traumas. Diseases due to physical agents; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; von Willebrand Factor - metabolism; Human; Transient response; Endothelial cell; Coronary artery; Precursor cell; Cardiovascular disease; Trauma; Vascularization; Arterial disease; Vascular disease; Burn; Mobilization; Growth factor receptor; Vascular endothelium growth factor; Bypass; Surgery; Blood vessel; Circulatory system; Lesion
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.res.88.2.167

ABSTRACT —Bone marrow (BM)–derived circulating endothelial precursor cells (CEPs) are thought to play a role in postnatal angiogenesis. Emerging evidence suggests that angiogenic stress of vascular trauma may induce mobilization of CEPs to the peripheral circulation. In this regard, we studied the kinetics of CEP mobilization in two groups of patients who experienced acute vascular insult secondary to burns or coronary artery bypass grafting (CABG). In both burn and CABG patients, there was a consistent, rapid increase in the number of CEPs, determined by their surface expression pattern of vascular endothelial growth factor receptor 2 (VEGFR2), vascular endothelial cadherin (VE-cadherin), and AC133. Within the first 6 to 12 hours after injury, the percentage of CEPs in the peripheral blood of burn or CABG patients increased almost 50-fold, returning to basal levels within 48 to 72 hours. Mobilized cells also formed late-outgrowth endothelial colonies (CFU-ECs) in culture, indicating that a small, but significant, number of circulating endothelial cells were BM-derived CEPs. In parallel to the mobilization of CEPs, there was also a rapid elevation of VEGF plasma levels. Maximum VEGF levels were detected within 6 to 12 hours of vascular trauma and decreased to baseline levels after 48 to 72 hours. Acute elevation of VEGF in the mice plasma resulted in a similar kinetics of mobilization of VEGFR2 cells. On the basis of these results, we propose that vascular trauma may induce release of chemokines, such as VEGF, that promotes rapid mobilization of CEPs to the peripheral circulation. Strategies to improve the mobilization and incorporation of CEPs may contribute to the acceleration of vascularization of the injured vascular tissue.