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BioMed Research International
Volume 2013 (2013), Article ID 217026, 6 pages
Research Article

Doxycycline Prevents Intimal Hyperplasia In Vitro and May Improve Patency of the Internal Thoracic Artery

1Department of Cardiac Surgery, School of Medicine, University Federico II, Via S. Pansini 5, 80131 Naples, Italy
2Department of Cardiology, Azienda Ospedaliera Santobono-Pausilipon, Via Posillipo 226, 80123 Naples, Italy

Received 23 April 2013; Accepted 17 June 2013

Academic Editor: M. Harold Laughlin

Copyright © 2013 Vito Mannacio et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Objectives. The development of intimal hyperplasia and graft failure is an important problem in cardiac surgery. A fundamental process in intimal hyperplasia is the degradation of extracellular matrix by metalloproteases which induces the vascular smooth-muscle cells migration and sets the scene for graft atherosclerosis. This study investigated whether doxycycline, a metalloproteases inhibitor, can prevent the intimal hyperplasia occurrence in cultured human internal mammary artery, thus extending graft patency. Methods. Segments of internal mammary artery from 20 consecutive patients were prepared and cultured for 2 weeks in serum-supplemented medium (control) or in medium supplemented with 10−5 M and 10−6 M doxycycline concentrations. Tissues were fixed, sectioned, and stained, and neointimal thickness was measured by computer-aided image analysis. Further sections were cultured and prepared for gel enzymography to measure the matrix metalloproteinase-2 and -9 levels. Results. At the end of the culture period, neointimal thickness was significantly ( ) dose-dependently reduced in samples treated with doxycycline when compared with controls. Gelatin enzymography demonstrated a reduction in values for both latent and active forms of metalloproteases. Conclusions. Doxycycline, in a model of internal mammary artery intimal hyperplasia, has a specific role in inhibiting metalloproteases activity and may prevent graft stenosis.