TY - JOUR
T1 - Platelet factor 4 mediates vascular smooth muscle cell injury responses
AU - Shi, Guanfang
AU - Field, David J.
AU - Long, Xiaochun
AU - Mickelsen, Deanne
AU - Ko, Kyung Ae
AU - Ture, Sara
AU - Korshunov, Vyacheslav A.
AU - Miano, Joseph M.
AU - Morrell, Craig N.
N1 - Funding Information:
C.N.M. is supported by R01HL093179 and R01HL094547 from the National Institutes of Health.
Publisher Copyright:
© 2013 by The American Society of Hematology.
PY - 2013/5/23
Y1 - 2013/5/23
N2 - Activated platelets release many inflammatory molecules with important roles in accelerating vascular inflammation. Much is known about platelet and platelet-derived mediator interactions with endothelial cells and leukocytes, but few studies have examined the effects of platelets on components of the vascular wall. Vascular smooth muscle cells (VSMCs) undergo phenotypic changes in response to injury including the production of inflammatory molecules, cell proliferation, cell migration, and a decline in the expression of differentiation markers. In this study, we demonstrate that the platelet-derived chemokine platelet factor 4 (PF4/CXCL4) stimulates VSMC injury responses both in vitro and in vivo in a mouse carotid ligation model. PF4 drives a VSMC inflammatory phenotype including a decline in differentiation markers, increased cytokine production, and cell proliferation. We also demonstrate that PF4 effects are mediated, in part, through increased expression of the transcription factor Krüppel-like factor 4. Our data indicate an important mechanistic role for platelets and PF4 in VSMC injury responses both in vitro and in vivo.
AB - Activated platelets release many inflammatory molecules with important roles in accelerating vascular inflammation. Much is known about platelet and platelet-derived mediator interactions with endothelial cells and leukocytes, but few studies have examined the effects of platelets on components of the vascular wall. Vascular smooth muscle cells (VSMCs) undergo phenotypic changes in response to injury including the production of inflammatory molecules, cell proliferation, cell migration, and a decline in the expression of differentiation markers. In this study, we demonstrate that the platelet-derived chemokine platelet factor 4 (PF4/CXCL4) stimulates VSMC injury responses both in vitro and in vivo in a mouse carotid ligation model. PF4 drives a VSMC inflammatory phenotype including a decline in differentiation markers, increased cytokine production, and cell proliferation. We also demonstrate that PF4 effects are mediated, in part, through increased expression of the transcription factor Krüppel-like factor 4. Our data indicate an important mechanistic role for platelets and PF4 in VSMC injury responses both in vitro and in vivo.
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U2 - 10.1182/blood-2012-09-454710
DO - 10.1182/blood-2012-09-454710
M3 - Article
C2 - 23568488
AN - SCOPUS:84880429183
SN - 0006-4971
VL - 121
SP - 4417
EP - 4427
JO - Blood
JF - Blood
IS - 21
ER -