Effect of folate on neointima formation and matrix metalloproteinase-9 expression after balloon injury in hyperhomocysteinemic rabbits.
BACKGROUND
It is known that hyperhomocysteinemia (Hhcy) is associated with the risk of restenosis after angioplasty. Folate can lower plasma homocysteine (Hcy) level and alleviate the Hhcy-induced neointima formation after balloon injury. This study aims to explore the mechanisms of folate in inhibiting neointima formation.


METHODS
24 New Zealand White rabbits were randomly divided into three groups: Control, 2% methionine (Meth) and 2% methionine+folate (Meth+folate). At the end of 8 experimental weeks, all rabbits underwent the balloon injury in abdominal aorta. 4 weeks following this procedure, plasma Hcy concentration, aortic maximal neointimal thickness (NT), neointimal area (NA), medial area (MA), and ratio of neointimal area to medial area (NA/MA), ultrastructure of vascular smooth muscle cells (VSMCs), and matrix metalloproteinase-9 (MMP-9) expression were detected by high performance liquid chromatography, histomorphometric analysis, transmission electron microscope (TEM) and real-time PCR, respectively.


RESULTS
It was observed in our study that Hcy concentration, NT, NA, NA/MA and the expression of MMP-9 mRNA were higher in the Meth group than in the control. VSMCs in media exhibited typical synthetic phenotype in the Meth group compared with the transitional state between contractile phenotype and synthetic phenotype in the control group. However, in the rabbits treated with folate, Hcy concentration, NT, NA and MMP-9 mRNA expression were lower than those in the Meth group. The phenotype of VSMCs was close to that in the control group.


CONCLUSIONS
This study suggested that folate could decrease the level of Hcy, reverse the Hhcy-induced exacerbation of neointima formation in rabbits following balloon injury, and the mechanisms in it may be related to the suppressive effect of folate on the expression of MMP-9 mRNA in arterial wall.
Liu
Fenye
F
Department of Traditional Chinese Medicine, Qilu Hospital Affiliated to Shandong University, Jinan 250012, Shandong, PR China.
Zhang
Jidong
J
Yu
Shudong
S
Wang
Rong
R
Wang
Bo
B
Lai
Liping
L
Yin
Huiqiu
H
Liu
Guilin
G
D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000201:enzymology / Q000293:injuries / Q000473:pathology; D002404:Catheterization / Q000009:adverse effects*; D005492:Folic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D020138:Hyperhomocysteinemia / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D011817:Rabbits; D017539:Tunica Intima / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology
D005492:Folic Acid; D020780:Matrix Metalloproteinase 9