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

Soo Lim, Min Kyong Moon, Hayley Shin, Tae Hyuk Kim, Bong Jun Cho, Min Kim, Ho Seon Park, Sung Hee Choi, Seong Hee Ko, Myung Hee Chung, In Kyu Lee, Hak Chul Jang, Young Bum Kim, Kyong Soo Park

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)383-393
Number of pages11
JournalCardiovascular Research
Volume90
Issue number2
DOIs
StatePublished - 1 May 2011

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S-Adenosylmethionine
Wounds and Injuries
Vascular Smooth Muscle
Smooth Muscle Myocytes
Adiponectin
Apoptosis
Tunicamycin
Hyperhomocysteinemia
Control Groups
Endoplasmic Reticulum Stress
Chemokine CCL2
Homocysteine
C-Reactive Protein
Type 2 Diabetes Mellitus
Cell Movement
Monocytes
Cultured Cells
Reactive Oxygen Species
Cardiovascular Diseases
Tumor Necrosis Factor-alpha

Keywords

  • Endoplasmic reticulum stress
  • Inflammation
  • Oxidative stress
  • Restenosis
  • S-Adenosylmethionine

Cite this

Lim, Soo ; Moon, Min Kyong ; Shin, Hayley ; Kim, Tae Hyuk ; Cho, Bong Jun ; Kim, Min ; Park, Ho Seon ; Choi, Sung Hee ; Ko, Seong Hee ; Chung, Myung Hee ; Lee, In Kyu ; Jang, Hak Chul ; Kim, Young Bum ; Park, Kyong Soo. / Effect of S-adenosylmethionine on neointimal formation after balloon injury in obese diabetic rats. In: Cardiovascular Research. 2011 ; Vol. 90, No. 2. pp. 383-393.
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Effect of S-adenosylmethionine on neointimal formation after balloon injury in obese diabetic rats. / Lim, Soo; Moon, Min Kyong; Shin, Hayley; Kim, Tae Hyuk; Cho, Bong Jun; Kim, Min; Park, Ho Seon; Choi, Sung Hee; Ko, Seong Hee; Chung, Myung Hee; Lee, In Kyu; Jang, Hak Chul; Kim, Young Bum; Park, Kyong Soo.

In: Cardiovascular Research, Vol. 90, No. 2, 01.05.2011, p. 383-393.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effect of S-adenosylmethionine on neointimal formation after balloon injury in obese diabetic rats

AU - Lim, Soo

AU - Moon, Min Kyong

AU - Shin, Hayley

AU - Kim, Tae Hyuk

AU - Cho, Bong Jun

AU - Kim, Min

AU - Park, Ho Seon

AU - Choi, Sung Hee

AU - Ko, Seong Hee

AU - Chung, Myung Hee

AU - Lee, In Kyu

AU - Jang, Hak Chul

AU - Kim, Young Bum

AU - Park, Kyong Soo

PY - 2011/5/1

Y1 - 2011/5/1

N2 - 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.

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KW - Inflammation

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