Mechanisms of arterial remodeling and neointima formation: an updated view on the chemokine system

The arterial vessel wall uniformly reacts to different kinds of injuries with structural changes characterized by neointimal formation, medial hypertrophy and constrictive remodeling leading to luminal stenosis. This detrimental sequela of vascular remodeling is clinically encountered in restenosis after percutaneous interventions, transplant vasculopathy or pulmonary hypertension. The chemokine network is centrally involved in each step of the remodeling process. Stromal cell-derived factor-1α (CXCL12) regulates vascular repair by smooth muscle progenitor cell (SPC) recruitment via their receptor CXCR4 contributing to neointima formation. Various chemokine–chemokine receptor pairs, such as MCP-1/CCR2, RANTES/CCR5 and Fractalkine/CX3CR1, induce monocyte and T cell infiltration of the injured artery thus expanding the neointimal tissue. MCP-1/CCR2 and Fractalkine/CX3CR1 also enhance the proliferation of neointimal SMCs. The CXC-Chemokine KC/Gro-α supports endothelial recovery through CXCR2 after denuding endothelial injury, which restricts neointimal growth. Thus, specific functions of particular chemokine–chemokine receptor pairs can be identified and serve as promising targets for drug treatment.

Section editor:Christian Weber – Institute for Molecular Cardiovascular Research, Medical Faculty, RWTH Aachen University, Aachen, Germany