TY - JOUR
T1 - Bone marrow-derived kruppel-like factor 10 controls reendothelialization in response to arterial injury
AU - Wara, Akm Khyrul
AU - Manica, Andre
AU - Marchini, Julio F.
AU - Sun, Xinghui
AU - Icli, Basak
AU - Tesmenitsky, Yevgenia
AU - Croce, Kevin
AU - Feinberg, Mark W.
PY - 2013/7
Y1 - 2013/7
N2 - 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. Approach and 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.
AB - 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. Approach and 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.
KW - Bone marrow
KW - Endothelial cells
KW - Kruppel-like factor 10
KW - Vascular system injuries
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U2 - 10.1161/ATVBAHA.112.300655
DO - 10.1161/ATVBAHA.112.300655
M3 - Article
C2 - 23685559
AN - SCOPUS:84879068872
SN - 1079-5642
VL - 33
SP - 1552
EP - 1560
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
IS - 7
ER -