CCN1 promotes the differentiation of endothelial progenitor cells and reendothelialization in the early phase after vascular injury.
Endothelial progenitor cells (EPCs) contribute to the process of reendothelialization and prevent neointimal formation after vascular injury. The present study was designed to investigate whether the cysteine-rich 61 (CYR61, CCN1), an important matricellular component of local vascular microenvironment, has effect on EPCs differentiation and reendothelialization in response to vascular injury in rat. Following balloon injury, CCN1 was rapidly induced and dynamically changed at vascular lesions. Overexpression of CCN1 by adenovirus (Ad-CCN1) accelerated reendothelialization and inhibited neointimal formation in the early phase (day 14) after vascular injury (p < 0.05), while no effect was shown on day 21. Ad-CCN1 treatment increased the adhering EPCs on the surface of injured vessels on day 7, and the ratio of GFP- and vWF-positive area to the total luminal length on day 14 was 2.3-fold higher in the Ad-CCN1-EPC-transplanted group than in controls. Consistent with these findings, CCN1-stimulated EPC differentiation in vitro and 20 genes were found differentially expressed during CCN1-induced EPC differentiation, including Id1, Vegf-b, Vegf-c, Kdr, Igf-1, Ereg, Tgf, Mdk, Ptn, Timp2, etc. Among them, negative transcriptional regulator Id1 was associated with CCN1 effect on EPC differentiation. Our data suggest that CCN1, from the microenvironment of injured vessels, enhances reendothelialization via a direct action on EPC differentiation, revealing a possible new mechanism underlying the process of vascular repair.
Yu
Yang
Y
Institute of Cardiovascular Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
Gao
Yu
Y
Qin
Jun
J
Kuang
Chun-Yan
CY
Song
Ming-Bao
MB
Yu
Shi-Yong
SY
Cui
Bin
B
Chen
Jian-Fei
JF
Huang
Lan
L
D000818:Animals; D020212:Carotid Artery Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D055515:Cysteine-Rich Protein 61 / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D005786:Gene Expression Regulation; D051798:Inhibitor of Differentiation Protein 1 / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014161:Transduction, Genetic
C501849:CCN1 protein, rat; D055515:Cysteine-Rich Protein 61; C497454:ID1 protein, rat; D051798:Inhibitor of Differentiation Protein 1; D012333:RNA, Messenger