17 beta-estradiol attenuates intimal hyperplasia and macrophage accumulation with a reduction in monocyte chemoattractant protein 1 expression in a vein graft model.
OBJECTIVE
Autogenous vein grafts are commonly used for arterial reconstructive procedures. Their success is limited by the development of intimal hyperplasia, a fibroproliferative disease that predisposes the grafts to occlusive stenosis. Our goal was to assess whether 17 beta-estradiol (E(2)) inhibits vein graft intimal hyperplasia coincident with a reduction in monocyte chemoattractant protein 1 (MCP-1) expression and macrophage accumulation.


METHODS
Male Lewis rats were implanted with time-release pellets that contained 0.5 mg E(2) (E5 group) or placebo (PL group). Epigastric vein to common femoral artery interposition grafts were harvested at 2, 4, 8, and 12 weeks after surgery. We assessed macrophage/monocytes numbers, proliferating cell nuclear antigen, MCP-1, and transforming growth factor-beta1 with use of immunohistochemistry. MCP-1 message expression was quantified by real-time polymerase chain reaction.


RESULTS
The time-release pellets raised the serum E(2) level to greater than 250 pg/mL on the day of surgery. Serum E(2) level declined to 43 +/- 13 pg/mL by 4 weeks and to baseline by 6 weeks. We found that the neointimal area ratio was reduced significantly in the E5 group at 2 and 4 weeks (45%, P <.05, and 68%, P < 0.05, respectively) relative to that in the PL group. The number of proliferating cells was reduced in the E5 group. There was a significant attenuation of MCP-1 expression and of the number of macrophages accumulating in the graft with E(2) treatment. Furthermore, MCP-1 messenger ribonucleic acid expression was also significantly attenuated in the E5 group at 4 weeks when compared to the PL group. There was no significant difference between the two groups in the expression of transforming growth factor-beta1.


CONCLUSIONS
E(2) treatment reduces vein-graft intimal hyperplasia coincident with a reduction in MCP-1 expression, macrophage accumulation, and cell proliferation.
Ryomoto
Masaaki
M
Department of Thoracic and Cardiovascular Surgery, Hyogo College of Medicine, Madison, WI, USA.
Wolff
Randal A
RA
Tomas
Jeffrey J
JJ
Miyamoto
Takashi
T
Hoch
John R
JR
D000009:Abdominal Muscles / Q000098:blood supply* / Q000473:pathology*; D000818:Animals; D018932:Chemokine CCL2 / Q000032:analysis* / Q000235:genetics*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology*; D004958:Estradiol / Q000494:pharmacology*; D005263:Femoral Artery / Q000473:pathology* / Q000601:surgery*; D015870:Gene Expression / Q000187:drug effects* / Q000235:genetics*; D006965:Hyperplasia / Q000139:chemically induced* / Q000473:pathology*; D008264:Macrophages / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D014680:Veins / Q000473:pathology / Q000637:transplantation
D018932:Chemokine CCL2; D004958:Estradiol