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Personne :
Mantovani, D. (Diego)

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Mantovani

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D. (Diego)

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Université Laval. Département de génie des mines, de la métallurgie et des matériaux

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ncf10497704

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Voici les éléments 1 - 2 sur 2
  • PublicationAccès libre
    Caveolin : a possible biomarker of degradable metallic materials toxicity on vascular cells
    (Elsevier, 2013-03-14) Couët, Jacques; Mantovani, D. (Diego); Purnama, Agung
    Iron-based materials could constitute an interesting option for cardiovascular biodegradable stent applications due to their appropriate ductility compared with their counterparts, magnesium alloys. However, the predicted degradation rate of pure iron is considered to be too slow for such applications. We explored manganese (35 wt.%) as an alloying element in combination with iron to circumvent this problem through powder metallurgical processing (Fe–35Mn). Manganese, on the other hand, is highly cytotoxic. We recently explored a new method to better characterize the safety of degradable metallic materials (DMMs) by establishing the gene expression profile (GEP) of cells (mouse 3T3 fibroblasts) exposed to Fe–35Mn degradation products in order to better understand their global response to a potentially cytotoxic DMM. We identified a number of up- and down-regulated genes and confirmed the regulation of a subset of them by quantitative real time polymerase chain reaction. Caveolin-1 (cav1), the structural protein of caveolae, small, smooth plasma membrane invaginations present in various differentiated cell types, was one of the most down-regulated genes in our GEPs. In the present study we further studied the potential of this 22 kDa protein to become a biomarker for cytotoxicity after exposure to degradable metallic elements. In order to better characterize cav1 expression in this context 3T3 mouse fibroblasts were exposed to either ferrous and manganese ions at cytostatic concentrations for 24 or 48 h. cav1 gene expression was not influenced by exposure to ferrous ions. On the other hand, exposure to manganese for 24 h reduced cav1 gene expression by about 30% and by >65% after 48 h compared with control 3T3 cells. The cav1 cellular protein content was reduced to the same extent. The same pattern of expression of cav3 (the muscle-specific caveolin subtype) was also observed in this study. This strong and reproducible pattern of regulation of caveolins thus indicates potential as a biomarker for the toxicity of DMM elements.
  • PublicationAccès libre
    Gene expression profile of mouse fibroblasts exposed to a biodegradable iron alloy for stents.
    (Elsevier, 2013-11-10) Couët, Jacques; Hermawan, Hendra; Mantovani, D. (Diego); Purnama, Agung; Champetier, Serge.
    Iron-based materials could constitute an interesting option for cardiovascular biodegradable stent applications due to their superior ductility compared to their counterparts - magnesium alloys. Since the predicted degradation rate of pure iron is considered slow, manganese (35% w/w), an alloying element for iron, was explored to counteract this problem through the powder metallurgy process (Fe-35 Mn). However, manganese presents a high cytotoxic potential; thus its effect on cells must first be established. Here, we established the gene expression profile of mouse 3T3 fibroblasts exposed to Fe-35 Mn degradation products in order to better understand cell response to potentially cytotoxic degradable metallic material (DMM). Mouse 3T3 cells were exposed to degradation products eluting through tissue culture insert filter (3 μm pore size) containing cytostatic amounts of 3.25 mg ml(-1) of Fe-35 Mn powder, 0.25 mg ml(-1) of pure Mn powder or 5 mg ml(-1) of pure iron powder for 24 h. We then conducted a gene expression profiling study from these cells. Exposure of 3T3 cells to Fe-35 Mn was associated with the up-regulation of 75 genes and down-regulation of 59 genes, while 126 were up-regulated and 76 down-regulated genes in the presence of manganese. No genes were found regulated for the iron powder. When comparing the GEP of 3T3 fibroblasts in the presence of Fe-35 Mn and Mn, 68 up-regulated and 54 down-regulated genes were common. These results were confirmed by quantitative RT-PCR for a subset of these genes. This GEP study could provide clues about the mechanism behind degradation products effects on cells of the Fe-35 Mn alloy and may help in the appraisal of its potential for DMM applications.