Stent material surface and glucose activate mononuclear cells of control, type 1 and type 2 diabetes subjects

Abstract

In stent restenosis (ISR) has been described as an unaccomplished tissue healing and its rate is particularly high in diabetic patients. Evidence has been collected which relates the formation of ISR proteoglycan-rich neointimal tissue to the accumulation and protracted activation of macrophages around the stent metal struts. Here, the in vitro activation of mononuclear cells adhering to stainless steel (a material of choice in stent manufacturing) from control and diabetic (types 1 and 2) subjects was assessed in the presence of different glucose levels. The results showed that cells from the control and type 1 diabetes groups produced significantly higher levels of TGF-beta1 when adhering on stainless steel (p = 0.04 and p = 0.01), but a significant PDGF-BB secretion was observed only in control subjects. When tested at physiological glucose concentration, the effect of the stainless steel on control cells was more pronounced. The present study shows that mononuclear cells adhering onto stainless steel secrete growth factors relevant to ISR. Cells from diabetic subjects seem to secrete relatively higher levels of PDGF under hyperglycaemic conditions regardless of the substrate exposed thus offering an explanation for the higher incidence of restenosis in these patients.

Nanoparticles of a different source induce different patterns of activation in key biochemical and cellular components of the host response

“…Previous work has shown that MMs are stimulated to produce relatively high levels of PDGF-BB when adhering on stainless steel surfaces, which are composed of iron, nickel and cobalt (Harrison et al 2007;Stewart et al in press). Therefore, these data seem to suggest that the analysed NPs were not able to activate MM biochemical pathways favouring granulation and fibrous tissue formation and that materials with similar chemistry can completely change their effects Host response to nanoparticles A. L. Guildford et al…”

Substrate‐induced phenotypical change of monocytes/macrophages into myofibroblast‐like cells: A new insight into the mechanism of in‐stent restenosis

“…Mononuclear cells were isolated from the heparinized blood within 1 h from venipuncture using a Histopaque-1077 medium (Sigma) as previously described. 3,11 The cells were washed three times in PBS and resuspended in RPMI-1640 medium (Fisher, UK). Cell viability was assessed using trypan blue staining and was always above 95%.…”

“…The treatment of the surfaces with PRP was performed to ensure the adsorption of plasma proteins onto the substrate surfaces, thus mimicking more closely the conditioning of the exposed surfaces occurring in vivo since the early phases of implantation. 3,11 The cells were incubated on EST, ECM, and Fib for 3 h at 378C, in 5% CO 2 , 95% air, then incubated overnight in growth medium enriched with 10% FCS for further 20 h. After 20 h, the medium supernatants were collected, centrifuged to eliminate unbound cells, and stored at 2708C until tested using ELISA kits for TGFb1 (DRG Diagnostic, Germany, catalogue number EIA-1864) and PDGF-BB (PeproTech EC, UK, catalogue no. 900-K04).…”

“…3,4 In the case of cells isolated from diabetic subjects, MM basal levels of these two growth factors appear to be relatively higher than in those from nondiabetic individuals regardless of the metal substrate challenge. 11 Indeed, the predisposition of MM to secrete TGF-1b and PDGF-BB when in contact with stainless steel may have a clinical significance, as these two growth factors are known to be potent activators of SMC proliferation, and they seem to play a key role in ISR development. 3,5,11 The in vitro model adopted in this study aimed at mimicking the adhesion of MM on three different substrates to which the cells are likely to be exposed during the early phases of stent implantation; (i) the surface of the implanted metal stent (i.e., electropolished stainless steel, EST), (ii) the collagen of the ECM) and (iii) the fibrin (Fib) of thrombi.…”

“…11 Indeed, the predisposition of MM to secrete TGF-1b and PDGF-BB when in contact with stainless steel may have a clinical significance, as these two growth factors are known to be potent activators of SMC proliferation, and they seem to play a key role in ISR development. 3,5,11 The in vitro model adopted in this study aimed at mimicking the adhesion of MM on three different substrates to which the cells are likely to be exposed during the early phases of stent implantation; (i) the surface of the implanted metal stent (i.e., electropolished stainless steel, EST), (ii) the collagen of the ECM) and (iii) the fibrin (Fib) of thrombi. The rationale in the choice of these substrates is that ECM collagen and thrombi are exposed following the damage of the endothelium and, together with EST, they are the substrates that circulating and plaque-resident MM are likely to face following stent implantation.…”