Interplay of CCR2 signaling and local shear force determines vein graft neointimal hyperplasia in vivo.
Leukocytes play a central role in vein graft neointimal hyperplasia, which is significantly augmented under low shear conditions. The current concept is that shear force regulates leukocyte adhesion predominately through up-regulation of chemokines and growth factors within the graft wall. Using rabbit and murine vein graft models, we demonstrate that CC chemokine receptor 2/monocyte chemoattractant protein-1 mediated monocyte recruitment and a low shear environment act synergistically to augment neointimal hyperplasia development and removal of either of the conditions leads to a significant reduction in neointimal thickening. We propose a novel concept that the shear stress response element phenotypically stems from the complex interplay of the biological and physical microenvironments.
Jiang
Zhihua
Z
Department of Surgery, University of Florida and the Malcom Randall VAMC, United States.
Yu
Peng
P
Tao
Ming
M
Ifantides
Cristos
C
Ozaki
C Keith
CK
Berceli
Scott A
SA
D000818:Animals; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000235:genetics; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006439:Hemodynamics; D006965:Hyperplasia / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D011183:Postoperative Complications / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011817:Rabbits; D054390:Receptors, CCR2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D033081:Shear Strength; D015398:Signal Transduction; D019737:Transplants / Q000009:adverse effects*; D017539:Tunica Intima / Q000378:metabolism* / Q000473:pathology*; D014680:Veins / Q000637:transplantation*
D018932:Chemokine CCL2; D054390:Receptors, CCR2