Sodium ferulate inhibits neointimal hyperplasia in rat balloon injury model.
OBJECTIVE
Neointimal formation after vessel injury is a complex process involving multiple cellular and molecular processes. Inhibition of intimal hyperplasia plays an important role in preventing proliferative vascular diseases, such as restenosis. In this study, we intended to identify whether sodium ferulate could inhibit neointimal formation and further explore potential mechanisms involved.


METHODS
Cultured vascular smooth muscle cells (VSMCs) isolated from rat thoracic aorta were pre-treated with 200 µmol/L sodium ferulate for 1 hour and then stimulated with 1 µmol/L angiotensin II (Ang II) for 1 hour or 10% serum for 48 hours. Male Sprague-Dawley rats subjected to balloon catheter insertion were administrated with 200 mg/kg sodium ferulate (or saline) for 7 days before sacrificed.


RESULTS
In presence of sodium ferulate, VSMCs exhibited decreased proliferation and migration, suppressed intracellular reactive oxidative species production and NADPH oxidase activity, increased SOD activation and down-regulated p38 phosphorylation compared to Ang II-stimulated alone. Meanwhile, VSMCs treated with sodium ferulate showed significantly increased protein expression of smooth muscle α-actin and smooth muscle myosin heavy chain protein. The components of Notch pathway, including nuclear Notch-1 protein, Jagged-1, Hey-1 and Hey-2 mRNA, as well as total β-catenin protein and Cyclin D1 mRNA of Wnt signaling, were all significantly decreased by sodium ferulate in cells under serum stimulation. The levels of serum 8-iso-PGF2α and arterial collagen formation in vessel wall were decreased, while the expression of contractile markers was increased in sodium ferulate treated rats. A decline of neointimal area, as well as lower ratio of intimal to medial area was observed in sodium ferulate group.


CONCLUSIONS
Sodium ferulate attenuated neointimal hyperplasia through suppressing oxidative stress and phenotypic switching of VSMCs.
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, PR China.
Jing
J
Zhang
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, PR China.
Jing
J
Chen
Department of Cardiology, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei, PR China.
Jian
J
Yang
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, PR China.
Changwu
C
Xu
Department of Cardiology, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei, PR China.
Jiawang
J
Ding
Department of Cardiology, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei, PR China.
Jun
J
Yang
Department of Ophthalmology, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei, China.
Qing
Q
Guo
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, PR China.
Qi
Q
Hu
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, PR China.
Hong
H
Jiang
D000800:Angioplasty, Balloon / Q000009:adverse effects; D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology; D002340:Carotid Artery Diseases / Q000188:drug therapy* / Q000209:etiology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003373:Coumaric Acids / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006965:Hyperplasia / Q000517:prevention & control; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology; D058426:Neointima / Q000188:drug therapy* / Q000209:etiology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
D003373:Coumaric Acids; D017382:Reactive Oxygen Species; D000804:Angiotensin II; C004999:ferulic acid