title: Bone marrow-derived Kruppel-like factor 10 controls reendothelialization in response to arterial injury.
abstract: OBJECTIVE
  The objective of this study was to investigate the role of Kruppel-like factor (KLF) 10, a zinc-finger transcription factor, in bone marrow (BM)-derived cell responses to arterial endothelial injury. Accumulating evidence indicates that BM-derived progenitors are recruited to sites of vascular injury and contribute to endothelial repair.
  
  
  RESULTS
  In response to carotid artery endothelial denudation, KLF10 mRNA expression was markedly increased in both BM and circulating lin(-) progenitor cells. To examine the specific role of KLF10 in arterial reendothelialization, we used 2 models of endothelial denudation (wire- and thermal-induced injury) of the carotid artery in wild-type (WT) and KLF10(-/-) mice. WT mice displayed higher areas of reendothelialization compared with KLF10(-/-) mice after endothelial injury using either method. BM transplant studies revealed that reconstitution of KLF10(-/-) mice with WT BM fully rescued the defect in reendothelialization and increased lin(-)CD34(+)kinase insert domain receptor(+) progenitors in the blood and injured carotid arteries. Conversely, reconstitution of WT mice with KLF10(-/-) BM recapitulated the defects in reendothelialization and peripheral cell progenitors. The media from cultured KLF10(-)/(-) BM progenitors was markedly inefficient in promoting endothelial cell growth and migration compared with the media from WT progenitors, indicative of defective paracrine trophic effects from KLF10(-)/(-) BM progenitors. Finally, BM-derived KLF10(-/-) lin(-) progenitors from reconstituted mice had reduced CXC-chemokine receptor 4 expression and impaired migratory responses.
  
  
  CONCLUSIONS
  Collectively, these observations demonstrate a protective role for BM-derived KLF10 in paracrine and homing responses important for arterial endothelial injury and highlight KLF10 as a possible therapeutic target to promote endothelial repair in vascular disease states.
authors.affiliation: Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Akm Khyrul
authors.initials: AK
authors.lastname: Wara
authors.forename: Andre
authors.initials: A
authors.lastname: Manica
authors.forename: Julio F
authors.initials: JF
authors.lastname: Marchini
authors.forename: Xinghui
authors.initials: X
authors.lastname: Sun
authors.forename: Basak
authors.initials: B
authors.lastname: Icli
authors.forename: Yevgenia
authors.initials: Y
authors.lastname: Tesmenitsky
authors.forename: Kevin
authors.initials: K
authors.lastname: Croce
authors.forename: Mark W
authors.initials: MW
authors.lastname: Feinberg
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D020212:Carotid Artery Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D002633:Chemotaxis; D017077:Culture Media, Conditioned / Q000378:metabolism; D004195:Disease Models, Animal; D051765:Early Growth Response Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D051741:Kruppel-Like Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019899:Paracrine Communication; D012333:RNA, Messenger / Q000378:metabolism; D054398:Receptors, CCR4 / Q000378:metabolism; D015398:Signal Transduction; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism*; D013997:Time Factors; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D057772:Vascular System Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; C515354:CCR4 protein, human; D017077:Culture Media, Conditioned; D051765:Early Growth Response Transcription Factors; C569958:KLF10 protein, mouse; D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; D054398:Receptors, CCR4; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Kruppel-like factor 10; bone marrow; endothelial cells; vascular system injuries