Colagenul matricei extracelulare în restenoza coronariană intra-stent

Abstract

Background: Extracellular matrix is underlined as an important factor regulating morphofunctional integrity of vascular wall, and is actively involved in vascular remodeling. Although collagen turnover activation is supported in mechanical artery injury, its character remains still unknown in the in-stent restenosis (ISR). The aim of this study is to evaluate the change of collagen type I and type III metabolism and metalloproteinase-2 (MMP2) expression in ISR. Material and methods: Using the confocal microscopy and immunochemistry techniques, the expression of collagen I and III, the markers of collagen I synthesis and degradation (PICP and CITP), as well as the expression of MMP2 and its tissue inhibitor (TIMMP2) have been assayed in the tissue pattern of ISR taken from 19 died patients. In 24 patients with ISR the markers of collagen I turnover were determined in blood also and compared with markers of 11 healthy persons. Results: The collagen I degradation is markedly increased in ISR and prevails over its synthesis while the collagen III degradation is enough preserved that led to collagen III/I ratio raising by 4-7 times already in minimal ISR. The CITP value is progressively increasing during restenosis exacerbation that is associated with a similar decline of PICP resulted consequently in a 7-10 fold elevation of the CITP/PICP ratio in muscular media of restenosis. Importantly to note that analogous changes of collagen type I turnover markers are established in blood in patients with ISR: PINP decreasing by 53.32% and CITP rise by 187.6%. The collagen I metabolism modification was accompanied by multiply MMP2 quantity increase and TIMPP2 diminution. Conclusions: 1. Extracellular matrix reorganization is a hallmark of the in-stent restenosis basically being exhibited by excessive collagen I degradation and preserved collagen III, splitting in conditions of MMP2/TIMMP2 ratio raising proportionally to ISR degree. 2. The shift of the circulating markers of collagen I turnover (PINP and CITP) is near to marker dynamics estimated in restenosis tissue that suggests their diagnostic and predictive role concerning ISR evolution.