SDF-1alpha/CXCR4 axis is instrumental in neointimal hyperplasia and recruitment of smooth muscle progenitor cells.
Recent evidence infers a contribution of smooth muscle cell (SMC) progenitors and stromal cell-derived factor (SDF)-1alpha to neointima formation after arterial injury. Inhibition of plaque area and SMC content in apolipoprotein E-deficient mice repopulated with LacZ+ or CXCR4-/- BM or lentiviral transfer of an antagonist reveals a crucial involvement of local SDF-1alpha and its receptor CXCR4 in neointimal hyperplasia via recruitment of BM-derived SMC progenitors. After arterial injury, SDF-1alpha expression in medial SMCs is preceded by apoptosis and inhibited by blocking caspase-dependent apoptosis. SDF-1alpha binds to platelets at the site of injury, triggers CXCR4- and P-selectin-dependent arrest of progenitor cells on injured arteries or matrix-adherent platelets, preferentially mobilizes and recruits c-kit-/platelet-derived growth factor receptor (PDGFR)-beta+/lineage-/sca-1+ progenitors for neointimal SMCs without being required for their differentiation. Hence, the SDF-1alpha/CXCR4 axis is pivotal for vascular remodeling by recruiting a subset of SMC progenitors in response to apoptosis and in concert with platelets, epitomizing its importance for tissue repair and identifying a prime target to limit lesion development.
Zernecke
Alma
A
Department of Molecular Cardiovascular Research, University Hospital, Rheinisch-Westfälische Technische Hochschule, Aachen, Germany.
Schober
Andreas
A
Bot
Ilze
I
von Hundelshausen
Philipp
P
Liehn
Elisa A
EA
Möpps
Barbara
B
Mericskay
Mathias
M
Gierschik
Peter
P
Biessen
Erik A
EA
Weber
Christian
C
D000818:Animals; D017209:Apoptosis; D001792:Blood Platelets / Q000502:physiology; D001854:Bone Marrow Cells / Q000502:physiology; D002454:Cell Differentiation; D002465:Cell Movement; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000502:physiology*; D005260:Female; D006965:Hyperplasia; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000032:analysis; D019718:Receptors, CXCR4 / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*; D017539:Tunica Intima / Q000473:pathology*
D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D019718:Receptors, CXCR4; D019009:Proto-Oncogene Proteins c-kit; D020797:Receptor, Platelet-Derived Growth Factor beta