Key result
SDF-1α/CXCR4 inhibition reduces neointimal plaque area and smooth muscle content in mice.
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.
No takes yet. Share an insight, caveat, or question.
Zernecke et al. (2005) studied Neointimal hyperplasia / arterial injury. CXCR4-/- bone marrow repopulation or lentiviral SDF-1alpha/CXCR4 antagonist transfer vs. LacZ+ bone marrow repopulation was evaluated on Plaque area, smooth muscle cell content, and neointimal hyperplasia. Inhibiting the SDF-1α/CXCR4 axis in apoE-deficient mice reduced neointimal plaque area and smooth muscle cell content by limiting bone marrow-derived progenitor recruitment.
Synapse has enriched 5 related papers. Consider them for comparative context: