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13‐MTD prevents neointimal formation in rat carotid arteries after balloon injury
Author(s) -
Wu ChiehHsi,
Sheu MingJyh
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a518
Subject(s) - restenosis , neointima , adventitia , proliferating cell nuclear antigen , vascular smooth muscle , cell growth , medicine , mapk/erk pathway , angiogenesis , apoptosis , cell , cancer research , endocrinology , kinase , chemistry , stent , biochemistry , smooth muscle
The pathological mechanism of restenosis is primarily attributed to excessive proliferation of vascular smooth muscle cells (VSMCs). The purpose of the study was to investigate the antiproliferative effects and the mechanisms of the 13‐methyltetradecanoic acid ¡]13‐MTD¡^ on VSMCs, as well as how 13‐MTD affects the prevention of balloon injury‐induced neointimal formation. To explore its molecular mechanism in regulating cell proliferation, we first showed that 13‐MTD markedly reduced the VSMCs proliferation via the inhibition of BrdU incorporation at 0.16£gM by 42%. This was further supported by a flowcytometric analysis showing an approximate 61% reduction of smooth muscle cells progressing to the S‐phase. In an in vivo study, 109 and 163 mg/kg of 13‐MTD was found to substantially reduced the neointimal formation in the rat carotid arteries adventitia by 47 and 58 %, respectively. The protein expression levels of proliferating cell nuclear antigen (PCNA), and Raf were both suppressed by 0.16£gM of 13‐MTD for approximately 78% and 82%. This was in agreement with the promoter activity of nuclear factor‐kappa B attenuated by 0.16£gM of 13‐MTD. Extracellular signal‐regulated kinases (Erk) involved in cell proliferation were also found to decrease by 13‐MTD. These observations provide a detailed mechanism of 13‐MTD in preventing cell proliferation thus as a potential pharmacological reagent in preventing balloon injury induced restenosis.