Rémi Martel

Cellular Effects of β-Particle Delivery on Vascular Smooth Muscle Cells and Endothelial Cells A Dose-Response Study

Background—Although endovascular radiotherapy inhibits neointimal hyperplasia, the exact cellular alterations induced by β irradiation remain to be elucidated. Methods and Results—We investigated in vitro the ability of 32P-labeled oligonucleotides to alter (1) proliferation of human and porcine vascular smooth muscle cells (VSMCs) and human coronary artery endothelial cells (ECs), (2) cell cycle progression, (3) cell viability and apoptosis, (4) cell migration, and (5) cell phenotype and morphological features. β radiation significantly reduced proliferation of VSMCs (ED50 1.10 Gy) and ECs (ED50 2.15 Gy) in a dose-dependent manner. Exposure to β emission interfered with cell cycle progression, with induction of G0/G1 arrest in VSMCs, without evidence of cell viability alteration, apoptosis, or ultrastructural changes. This strategy also proved to efficiently inhibit VSMC migration by 80% and induce contractile phenotype appearance, as shown by the predominance of α-actin immunostaining in β-irradiated ce...

Effect of ionizing radiation on thymidine uptake, differentiation, and VEGFR2 receptor expression in endothelial cells: The role of VEGF165

Purpose: Late thrombosis of irradiated vascular segments may be the consequence of endothelial cell (EC) dysfunction after radiation therapy. We investigated the effects of β ionizing radiation on human EC viability, thymidine uptake, and differentiation. Methods and Materials: Endothelial cells were exposed to 32P-labeled DNA oligonucleotides in incremental doses of 2, 6, and 10 Gy. The modulation of the VEGFR2 receptor expression after irradiation and the overall potential radioprotective effect of VEGF165 on these functions were assayed. Results: A dose-dependent inhibitory effect of β irradiation on ECs’ thymidine uptake and differentiation was observed. EC viability, however, was not affected at levels of radiation up to 10 Gy. VEGF165 proved to have a radioprotective effect as ECs’ thymidine uptake, after radiation doses of 2, 6, and 10 Gy, was increased by 1.5-, 2-, and 4-fold, respectively, in the presence of 10 ng/ml of VEGF165 (p < 0.05 vs. LacZ). This concentration of VEGF165 also proved beneficial in maintaining cell differentiation at 16 h postirradiation when compared to controls. These biologic effects were in direct correlation with the upregulation of VEGFR2 receptor expression in irradiated ECs. Conclusions: β irradiation interacts directly with EC functions by significantly reducing their ability to differentiate and proliferate, associated with upregulation of VEGFR2. These effects can be prevented in part by pretreating cells with VEGF165, an effect potentially favored by the upregulation of VEGFR2 receptor expression after irradiation.