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Lardenoye JH, de Vries MR, Deckers M, et al. Inhibition of intimal hyperplasia by the tetracycline derived mmp inhibitor doxycycline in vein graft disease in vitro and in vivo. EuroIntervention. 2005;1(2):236-43
Lardenoye, J. H., de Vries, M. R., Deckers, M., van Lent, N., Hanemaaijer, R., van Bockel, J. H., & Quax, P. H. (2005). Inhibition of intimal hyperplasia by the tetracycline derived mmp inhibitor doxycycline in vein graft disease in vitro and in vivo. EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology, 1(2), 236-43.
Lardenoye, J H P, et al. "Inhibition of intimal hyperplasia by the tetracycline derived mmp inhibitor doxycycline in vein graft disease in vitro and in vivo." EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology vol. 1,2 (2005): 236-43.
Lardenoye JH, de Vries MR, Deckers M, van Lent N, Hanemaaijer R, van Bockel JH, Quax PH. Inhibition of intimal hyperplasia by the tetracycline derived mmp inhibitor doxycycline in vein graft disease in vitro and in vivo. EuroIntervention. 2005 Aug;1(2):236-43. PMID: 19758909.
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EuroIntervention. 2005 Aug;1(2):236-43.

Inhibition of intimal hyperplasia by the tetracycline derived mmp inhibitor doxycycline in vein graft disease in vitro and in vivo.

EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology

J H P Lardenoye, M R de Vries, M Deckers, N van Lent, R Hanemaaijer, J H van Bockel, P H A Quax

Affiliations

  1. TNO Prevention and Health, Gaubius Laboratory, Leiden, The Netherlands.

PMID: 19758909

Abstract

AIMS: Intimal hyperplasia, characterised by smooth muscle cell migration and proliferation, requires extracellular matrix degradation which is mediated by matrix metalloproteinases (MMPs). In this study, the effect of tetracycline derived doxycycline, a specific MMP inhibitor of both activity and synthesis, on intimal hyperplasia in vitro and in vivo was assessed.

METHODS AND RESULTS: Segments of human saphenous veins were cultured for 4 weeks in absence or presence of doxycycline (10microg/ml) (n=6). A 81% inhibition in intimal hyperplasia was observed in the doxycycline treated segments compared to controls. To assess the effect of doxycycline on intimal hyperplasia in vivo, perivascular cuffs were placed around femoral arteries in mice with or without doxycycline in the drinking water (3 mg/ml). In this in vivo model for intimal hyperplasia doxycycline significantly reduced (68%, n=6) intimal hyperplasia when compared to controls. In addition the effect of doxycycline on vein graft thickening was assessed in a murine venous interposition model. In this in vivo model vein graft thickening was reduced by 35 % in the doxycycline treated mice (3 mg/ml in drinking water). Furthermore, a reduction in vascular MMP expression was observed in these mice.

CONCLUSION: Treatment with tetracycline derived doxycycline results in significant inhibition of intimal hyperplasia in vitro and in vivo and may be an effective strategy to prevent post interventional restenosis and vein graft disease.

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