Role of Interleukin-18 in vascular injury: a new pharmacological target for the prevention of restenosis

Grassia, Gianluca (2006) Role of Interleukin-18 in vascular injury: a new pharmacological target for the prevention of restenosis. [Tesi di dottorato] (Inedito)

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Abstract

Background: Studies in humans as well as in animal models suggest that interleukin-18 (IL-18) plays a crucial role in vascular pathologies. IL-18 is a strong predictor of cardiovascular death in angina and is involved in atherotic plaque destabilization. Higher IL-18 plasma levels are also associated with restenosis after coronary artery angioplasty performed in patients with acute myocardial infarction. We investigated the effective role of IL-18 in neointima formation in a rat model of vascular injury, known as balloon angioplasty. Methods and Results: Endothelial denudation of the left carotid artery was performed by using a balloon embolectomy catheter. Increased expression of IL-18 and IL-18Rα/β mRNA was detectable in carotid arteries from day 2 to 14 after angioplasty. The active form of IL-18 was highly expressed in injured arteries. Strong immunoreactivity for IL-18 was detected in the medial smooth muscle cells at day 2 and 7 after balloon injury and in proliferating/migrating smooth muscle cells in neointima at day 14. Moreover, serum concentrations of IL-18 were significantly higher among rats subjected to vascular injury. Rats treatment with neutralizing rabbit anti-rat IL-18 IgG significantly reduced by 27% (P<0.01) neointima formation. In addition, IL-18 neutralization reduced number of proliferating cells, inhibited IFN-γ, IL-6, IL-8 mRNA expression and nuclear factor-κB activation in injured arteries. Conclusions: These results identify for the first time a critical role for IL-18 in neointima formation in a rat model of vascular injury and suggest a potential role for IL-18 neutralization in reduction of neointima development and progression.

Tipologia di documento:Tesi di dottorato
Parole chiave:Balloon angioplasty, Carotid arteries, Interleukin-18
Settori scientifico-disciplinari MIUR:Area 05 Scienze biologiche > BIO/04 FISIOLOGIA VEGETALE
Area 05 Scienze biologiche > BIO/14 FARMACOLOGIA
Area 05 Scienze biologiche > BIO/10 BIOCHIMICA
Area 03 Scienze chimiche > CHIM/10 CHIMICA DEGLI ALIMENTI
Area 03 Scienze chimiche > CHIM/08 CHIMICA FARMACEUTICA
Area 03 Scienze chimiche > CHIM/06 CHIMICA ORGANICA
Area 03 Scienze chimiche > CHIM/09 FARMACEUTICO TECNOLOGICO APPLICATIVO
Area 05 Scienze biologiche > BIO/15 BIOLOGIA FARMACEUTICA
Coordinatori della Scuola di dottorato:
Coordinatore del Corso di dottoratoe-mail (se nota)
Abignente, Enrico
Tutor della Scuola di dottorato:
Tutor del Corso di dottoratoe-mail (se nota)
Ialenti, Armando
Stato del full text:Accessibile
Data:2006
Numero di pagine:80
Istituzione:Università degli Studi di Napoli Federico II
Dipartimento o Struttura:Chimica Farmaceutica e Tossicologica
Tipo di tesi:Dottorato
Stato dell'Eprint:Inedito
Denominazione del dottorato:Scienza del farmaco
Ciclo di dottorato:XVIII
Numero di sistema:712
Depositato il:31 Luglio 2008
Ultima modifica:04 Febbraio 2009 09:39

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