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BMC Cardiovascular Disorders

, 6:32

First Online: 07 July 2006Received: 29 March 2006Accepted: 07 July 2006DOI: 10.1186-1471-2261-6-32

Cite this article as: Voisard, R., Höb, J., Baur, R. et al. BMC Cardiovasc Disord 2006 6: 32. doi:10.1186-1471-2261-6-32

Abstract

BackgroundLow dose irradiation LDI of uninjured segments is the consequence of the suggestion of many authors to extend the irradiation area in vascular brachytherapy to minimize the edge effect. Atherosclerosis is a general disease and the uninjured segment close to the intervention area is often atherosclerotic as well, consisting of neointimal smooth muscle cells SMC and quiescent monocytes MC. The current study imitates this complex situation in vitro and investigates the effect of LDI on proliferation of SMC and expression of intercellular adhesion molecule-1 ICAM-1 in MC.

MethodsPlaque tissue from advanced primary stenosing lesions of human coronary arteries 9 patients, age: 61 ± 7 years was extracted by local or extensive thrombendarterectomy. SMC were isolated and identified by positive reaction with smooth muscle α-actin. MC were isolated from buffy coat leukocytes using the MACS cell isolation kit. For identification of MC flow-cytometry analysis of FITC-conjugated CD68 and CD14 FACScan was applied. SMC and MC were irradiated using megavoltage photon irradiation CLINAC2300 C-D, VARIAN, USA of 6 mV at a focus-surface distance of 100 cm and a dose rate of 6 Gy min with single doses of 1 Gy, 4 Gy, and 10 Gy. The effect on proliferation of SMC was analysed at day 10, 15, and 20. Secondly, total RNA of MC was isolated 1 h, 2 h, 3 h, and 4 h after irradiation and 5 μg of RNA was used in standard Northern blot analysis with ICAM-1 cDNA-probes.

ResultsBoth inhibitory and stimulatory effects were detected after irradiation of SMC with a dose of 1 Gy. At day 10 and 15 a significant antiproliferative effect was found; at day 20 after irradiation cell proliferation was significantly stimulated. Irradiation with 4 Gy and 10 Gy caused dose dependent inhibitory effects at day 10, 15, and 20. Expression of ICAM-1 in human MC was neihter inhibited nor stimulated by LDI.

ConclusionThus, the stimulatory effect of LDI on SMC proliferation at day 20 days after irradiation may be the in vitro equivalent of a beginning edge effect. Extending the irradiation area in vascular brachytherapy in vivo may therefore merely postpone and not inhibit the edge effect. The data do not indicate that expression of ICAM-1 in quiescent MC is involved in the process.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2261-6-32 contains supplementary material, which is available to authorized users.

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Autor: Rainer Voisard - Jochen Höb - Regine Baur - Tina Herter - Andreas Hannekum - Vinzenz Hombach

Fuente: https://link.springer.com/







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