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

• Published in: Cardiovascular research 2011-05, Vol.90 (2), p.383-393
• Main Authors: SOO LIM, MIN KYONG MOON, IN KYU LEE, HAK CHUL JANG, KIM, Young-Bum, KYONG SOO PARK, SHIN, Hayley, TAE HYUK KIM, BONG JUN CHO, KIM, Min, HO SEON PARK, SUNG HEE CHOI, KO, Seong-Hee, MYUNG HEE CHUNG
• Format: Article
• Language: English
• Subjects: Angioplasty, Balloon - adverse effects; Animals; Apoptosis - drug effects; Biological and medical sciences; Biomarkers - metabolism; Cardiology. Vascular system; Carotid Artery Diseases - complications; Carotid Artery Diseases - drug therapy; Carotid Artery Diseases - immunology; Cell Division - drug effects; Cells, Cultured; Diabetes Mellitus, Type 2 - complications; Diabetes. Impaired glucose tolerance; Disease Models, Animal; Dose-Response Relationship, Drug; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Insulin Resistance; Male; Medical sciences; Metabolic diseases; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - pathology; Neointima - complications; Neointima - drug therapy; Neointima - immunology; Obesity; Oxidative Stress - drug effects; Rats; Rats, Inbred OLETF; S-Adenosylmethionine - pharmacology; Vasculitis - complications; Vasculitis - drug therapy; Vasculitis - immunology
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1093/cvr/cvr009

The 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. Otsuka Long-Evans 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 1 week before carotid injury to 2 weeks thereafter. SAM treatment for 3 weeks 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. These 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.