Abstract | BACKGROUND: Aging-associated functional impairment of endothelial progenitor cells (EPCs) contributes to delayed re-endothelialization after vascular injury and exaggerated intimal hyperplasia (IH). This study tested if bone marrow (BM) rejuvenation accelerates post-injury re-endothelialization in aging mice. METHODS AND RESULTS: Using BM transplantation (BMT(Gfp→Wild)), young(Gfp) to young(Wild) (YTY), old(Gfp) to old(Wild) (OTO), young(Gfp) to old(Wild) (YTO), and old(Gfp) to young(Wild) (OTY) groups were created. After vascular injury, IH was significantly greater in the old group than the young group (P<0.001). BM rejuvenation (YTO) significantly accelerated re-endothelialization and attenuated IH. Compared with the OTO group, the YTY and YTO groups had earlier and greater EPC-derived re-endothelialization (P<0.001). The number of Sca-1(+)KDR(+) EPCs mobilized in the circulation induced by vascular injury was higher in young, YTO, and YTY mice than in old mice (P<0.05). Sca-1(+) BM cells from the young, YTO, and YTY groups had better migration and adhesion capacities than those from the old group (P<0.05). The increase in blood vascular endothelial growth factor ( VEGF) levels after vascular injury was higher in young than in old mice. PI3K, Akt, and FAK pathways played a pivotal role in VEGF-associated EPC migration. Specifically, EPCs from young and YTO mice, compared with old mice, demonstrated stronger FAK phosphorylation after VEGF stimulation. CONCLUSIONS: EPCs play a critical role in vascular repair in aging mice. BM rejuvenation accelerates re-endothelialization by improving EPC function.
|
Authors | Chao-Hung Wang, Ming-Feng Lee, Ning-I Yang, Hsiu-Fu Mei, Sheng-Yuan Lin, Wen-Chin Cherng |
Journal | Circulation journal : official journal of the Japanese Circulation Society
(Circ J)
Vol. 77
Issue 12
Pg. 3045-53
( 2013)
ISSN: 1347-4820 [Electronic] Japan |
PMID | 24042255
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- VEGFA protein, human
- Vascular Endothelial Growth Factor A
- Phosphatidylinositol 3-Kinases
- Focal Adhesion Kinase 1
- Ptk2 protein, mouse
- Proto-Oncogene Proteins c-akt
|
Topics |
- Aging
(genetics, metabolism, pathology)
- Allografts
- Animals
- Bone Marrow Transplantation
- Cell Movement
(genetics)
- Endothelial Cells
(metabolism, pathology)
- Focal Adhesion Kinase 1
(genetics, metabolism)
- Hyperplasia
- Male
- Mice
- Mice, Transgenic
- Phosphatidylinositol 3-Kinases
(genetics, metabolism)
- Proto-Oncogene Proteins c-akt
(genetics, metabolism)
- Signal Transduction
(genetics)
- Stem Cells
(metabolism, pathology)
- Tunica Intima
(metabolism, pathology)
- Vascular Endothelial Growth Factor A
(genetics, metabolism)
- Vascular System Injuries
(genetics, metabolism, pathology)
|