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

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...

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Autores principales: Mannacio, Vito, Di Tommaso, Luigi, Antignano, Anita, Di Tommaso, Ettorino, Stassano, Paolo, Vosa, Carlo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3766600/
https://www.ncbi.nlm.nih.gov/pubmed/24063001
http://dx.doi.org/10.1155/2013/217026
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author Mannacio, Vito
Di Tommaso, Luigi
Antignano, Anita
Di Tommaso, Ettorino
Stassano, Paolo
Vosa, Carlo
author_facet Mannacio, Vito
Di Tommaso, Luigi
Antignano, Anita
Di Tommaso, Ettorino
Stassano, Paolo
Vosa, Carlo
author_sort Mannacio, Vito
collection PubMed
description 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 (P = 0.001) 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.
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spelling pubmed-37666002013-09-23 Doxycycline Prevents Intimal Hyperplasia In Vitro and May Improve Patency of the Internal Thoracic Artery Mannacio, Vito Di Tommaso, Luigi Antignano, Anita Di Tommaso, Ettorino Stassano, Paolo Vosa, Carlo Biomed Res Int Research Article 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 (P = 0.001) 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. Hindawi Publishing Corporation 2013 2013-08-22 /pmc/articles/PMC3766600/ /pubmed/24063001 http://dx.doi.org/10.1155/2013/217026 Text en Copyright © 2013 Vito Mannacio et al. https://creativecommons.org/licenses/by/3.0/ 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.
spellingShingle Research Article
Mannacio, Vito
Di Tommaso, Luigi
Antignano, Anita
Di Tommaso, Ettorino
Stassano, Paolo
Vosa, Carlo
Doxycycline Prevents Intimal Hyperplasia In Vitro and May Improve Patency of the Internal Thoracic Artery
title Doxycycline Prevents Intimal Hyperplasia In Vitro and May Improve Patency of the Internal Thoracic Artery
title_full Doxycycline Prevents Intimal Hyperplasia In Vitro and May Improve Patency of the Internal Thoracic Artery
title_fullStr Doxycycline Prevents Intimal Hyperplasia In Vitro and May Improve Patency of the Internal Thoracic Artery
title_full_unstemmed Doxycycline Prevents Intimal Hyperplasia In Vitro and May Improve Patency of the Internal Thoracic Artery
title_short Doxycycline Prevents Intimal Hyperplasia In Vitro and May Improve Patency of the Internal Thoracic Artery
title_sort doxycycline prevents intimal hyperplasia in vitro and may improve patency of the internal thoracic artery
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3766600/
https://www.ncbi.nlm.nih.gov/pubmed/24063001
http://dx.doi.org/10.1155/2013/217026
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