Effect of S-adenosylmethionine on neointimal formation after balloon injury in obese diabetic rats

AimsThe association between hyperhomocysteinaemia and cardiovascular disease has been attributed to low levels of S-adenosylmethionine (SAM), a metabolic intermediate of homocysteine. However, the role of SAM in the development of restenosis has not been explored. Therefore, we investigated the effects of SAM on neointimal formation after balloon injury in obese diabetic rats and cultured cells.Methods and resultsOtsuka LongEvans Tokushima fatty rats were divided into the following three groups: control (normal saline); SAM15; and SAM30 (15 and 30 mg/kg per day, respectively; n =10 per group). SAM was administered orally from 1week before carotid injury to 2weeks thereafter. SAM treatment for 3weeks caused a significant dose-dependent reduction in the intima-to-media ratio. SAM treatment significantly reduced the proliferation of vascular smooth muscle cells (VSMCs) and induced more apoptosis than was observed in the control group. This effect was accompanied by reduced circulating levels of high-sensitivity C-reactive protein and monocyte chemoattractant protein-1, reduced urine 8-hydroxy-2′-deoxyguanosine (8-OHdG), and increased adiponectin. Intima-to-media ratio correlated significantly with the levels of inflammatory markers, adiponectin, and 8-OHdG. In vitro experiments demonstrated that VSMC proliferation and migration and the adhesion of monocytes decreased in response to SAM. SAM treatment also reduced tumour necrosis factor-α-induced reactive oxygen species and tunicamycin-induced GRP78 expression in VSMCs.ConclusionThese findings suggest that SAM exerts protective effects against restenosis after balloon injury in a rat model of type 2 diabetes by reducing the proliferation and inducing the apoptosis of VSMCs, modifying the inflammatory processes and reducing oxidative and endoplasmic reticulum stresses.