Zinc reduces intimal hyperplasia in the rat carotid injury model.
BACKGROUND
The response to arterial injury following balloon dilatation is known to involve proliferative and inflammatory processes. The current widespread use of stents to maintain arterial patency not only does not eliminate but possibly exaggerates the proliferative and inflammatory phenotype and although drug-eluting stents are available, their long-term safety is yet to be determined. Zinc is a trace element that serves as a cofactor of many enzymes. Interestingly, it has been shown to have anti-inflammatory and anti-proliferative properties. We thus sought to investigate its effect on smooth muscle cell proliferation and intimal thickening in the rat carotid artery injury model.


RESULTS
Smooth muscle cells (SMC) were cultured from carotid arteries of rats and proliferation was assessed by thymidine incorporation after exposure to different concentrations of zinc. Next, carotid artery injury was induced in rats by balloon dilatation and they were either treated with I.P injections of zinc or PBS for 2 weeks until sacrifice for assessment of neointimal formation and lumen area. Zinc inhibited in vitro SMC proliferation in a dose-dependent manner. In vivo, zinc treatment resulted in a 50% reduction in neointimal area and a significant decrease in neointimal/media ratio with no significant change in lumen area.


CONCLUSIONS
Thus, zinc appears to reduce neointimal growth and should be tested by local delivery systems including stent coatings.
Berger
Michael
M
The Cardiovascular Research Laboratory, The Department of Cardiology, Elias Sourasky, Tel Aviv Medical Center, Tel Aviv University Sackler Faculty of Medicine, 6 Weizmann St., Tel Aviv, Israel.
Rubinraut
Esthie
E
Barshack
Iris
I
Roth
Arie
A
Keren
Gad
G
George
Jacob
J
D000818:Animals; D020212:Carotid Artery Injuries / Q000209:etiology / Q000473:pathology*; D017536:Carotid Artery, Common / Q000473:pathology*; D002404:Catheterization / Q000009:adverse effects; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D006965:Hyperplasia / Q000517:prevention & control; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017539:Tunica Intima / Q000473:pathology*; D015032:Zinc / Q000494:pharmacology / Q000627:therapeutic use*
D015032:Zinc