Arterial reconstruction procedures, including balloon angioplasty, stenting and coronary artery bypass, are used to restore blood flow in atherosclerotic arteries. Restenosis of these arteries has remained a major limitation of the application of these procedures, especially in the case of balloon angioplasty. Post-angioplasty restenosis results from two major processes: neointimal formation and constrictive remodelling. Neointimal formation is initiated by arterial injury with a resultant loss of contractile phenotype in tunica media, leading to VSMC [vascular SM (smooth muscle) cell] migration from the tunica media to the intima. Migrated VSMCs contribute to the intimal thickening by the excessive synthesis of ECM (extracellular matrix) and proliferation. However, increased neointimal mass is not solely responsible for luminal narrowing. Inward constrictive remodelling is also considered as a major cause of delayed failure of angioplasty. At later stages after angioplasty, the increase in contractile forces leads to lumen narrowing. Recent studies show that SM contractile proteins are re-expressed in the neointima, concomitant with late lumen loss. Therefore one important question is whether the restoration of contractile phenotype, which can suppress VSMC migration, is favourable or detrimental. In this review, the importance of viewing restenosis as a multistage process is discussed. Different stages of restenosis occur in a sequential manner and are related to each other, but in each stage a different strategy should be taken into consideration to reduce restenosis. Defining the role of each process not only reshapes the current concept, but also helps us to target restenosis with more efficacy.

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