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Title: The influence of stent material and diabetes on macrophages trans-differentiation pathways in the progression of in-stent restenosis
Author: Poletti, Tiziano
ISNI:       0000 0004 5348 5451
Awarding Body: University of Brighton
Current Institution: University of Brighton
Date of Award: 2014
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The outcome of the deployment of cardiovascular stents in coronary arteries compromised by atherosclerosis may be affected by the deposition of a myofibroblast-driven neointimal tissue and consequent re-blockage of the vessel lumen known as instent restenosis (ISR). Its incidence is particularly high in people with diabetes unless drug-eluting stents (DES) are implanted as alternatives to the traditional bare metal stents (BMS) made of stainless steel (ST). However, the long-term outcome of the use of DES is under debate due to evidence of late thrombosis. Monocytes/macrophages (MM) play a key role in ISR participating in the different phases of the host response to the implant. This in-vitro study investigates differences in the distribution and response of MM that may be significant for a better understanding of the causes of the increased ISR occurrence among diabetic patients, particularly focusing on the trans-differentiation potential of MM into myofibroblast-like cells when in contact with ST. The overnight incubation of MM freshly isolated from blood from healthy donors (n=6) in high glucose (4S00mglL) and high free fatty acid (sodium palmitate 0.4mM) concentrations, alone or in combination, aimed at creating a diabetes-mimicking experimental model. MM response to ST seemed exacerbated by the syoergistic effect of the palmitate and glucose as shown by the occurrence of features characteristic of activation as well as by their trend to fuse into the formation of giant cells as shown by scanning electron microscopy. Similarly results from RT-PCR (n=6) suggested an increase in the expression of the mRNA for HAS3, the enzyme responsible for the synthesis of low molecular weight hyaluronic acid characteristic of the inflammatory process. Furthermore, the presence of MM positive for a-actin, as shown by immunocytochemistry, seemed to confirm the occurrence of early changes in their phenotype. This was accompanied by a significant (p
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: B000 Health Professions