L-theanine attenuates neointimal hyperplasia via suppression of vascular smooth muscle cell phenotypic modulation

Abstract Neointimal hyperplasia is a prominent pathological phenomenon in the process of stent restenosis. Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) play major pathological processes involved in the development of restenosis. L-theanine, one of the major amino acid components in green tea, has been reported to improve vascular function. Here we display the effects of L-theanine on neointima formation and the underlying mechanism. In the rat carotid-artery balloon-injury model, L-theanine greatly inhibited neointima formation and prevented VSMCs from a contractile phenotype switching to a synthetic phenotype. In vitro study showed that L-theanine significantly inhibited PDGF-BB-induced VSMC proliferation and migration, which was comparable with the effect of L-theanine on AngII-induced VSMC proliferation and migration. Western blot analysis demonstrated that L-theanine suppressed PDGF-BB and AngII-induced reduction of SMA and SM22α and increment of OPN, suggesting that L-theanine inhibited the transformation of VSMCs from contractile to the synthetic phenotype. Further experiments showed that L-theanine exhibits potential preventive effects on neointimal hyperplasia and related vascular remodeling via inhibition of phosphorylation of Elk-1 and activation of MAPK1. The present study provides the new experimental evidence that L-theanine has potential clinical application as an anti-restenosis agent for the prevention of restenosis.