SDF-1α/CXCR4 Axis Is Instrumental in Neointimal Hyperplasia and Recruitment of Smooth Muscle Progenitor Cells

Abstract

Abstract-Recent evidence infers a contribution of smooth muscle cell (SMC) progenitors and stromal cell-derived factor (SDF)-1␣ to neointima formation after arterial injury. Inhibition of plaque area and SMC content in apolipoprotein E-deficient mice repopulated with LacZ ϩ or CXCR4 Ϫ/Ϫ BM or lentiviral transfer of an antagonist reveals a crucial involvement of local SDF-1␣ and its receptor CXCR4 in neointimal hyperplasia via recruitment of BM-derived SMC progenitors. After arterial injury, SDF-1␣ expression in medial SMCs is preceded by apoptosis and inhibited by blocking caspase-dependent apoptosis. SDF-1␣ 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 Ϫ /platelet-derived growth factor receptor (PDGFR)-␤ ϩ /lineage Ϫ /sca-1 ϩ progenitors for neointimal SMCs without being required for their differentiation. Hence, the SDF-1␣/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.

Engagement of αIIbβ3 (GPIIb/IIIa) with ανβ3 Integrin Mediates Interaction of Melanoma Cells with Platelets

“…1). It is known that platelets express and secrete the CXC chemokine SDF-1␣ (CXCL12), which has recently been implicated in attracting circulating cells to the vascular wall (27,42,43). Expression of the cognate receptor for SDF-1␣, CX-chemokine receptor 4 (CXCR4) has been shown to crucially support organ-selective hematogenous metastasis of melanoma cells to the lung (32).…”

Immobilization Stress Inhibits Intimal Fibromuscular Proliferation in the Process of Arterial Remodeling in Rats

“…If the progenitor cells had invaded and proliferated, the media structure should have been disarranged. Moreover, on the third day after denudation, the progenitor cells had not fully been recruited in the media (53,54). Thus, the PCNApositive cells were thought to be pre-existing medial SMCs.…”

The SDF-1–CXCR4 signaling pathway: a molecular hub modulating neo-angiogenesis

“…Finally, SDF-1 contributes to the stabilization of neo-vessel formation by recruiting CXCR4 + PDGFR + ckit + smooth muscle progenitor cells during recovery from vascular injury [64]. Although Aghi et al suggested that SDF-1 did not recruit pericytes in glioma models [58], it is likely that specific tumor types could require recruitment of BM-derived CXCR4 + pericyte progenitors in a SDF-1-dependent manner [65].…”