Bone Marrow–Derived Kruppel-Like Factor 10 Controls Reendothelialization in Response to Arterial Injury
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+KDR+ 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 CXCR4 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.
- Received December 29, 2012.
- Accepted May 6, 2013.
- © 2013 American Heart Association, Inc.