Matrix Aging and Aneurysm

Overview

During their biological life, proteins undergo molecular aging due to many non-enzymatic post-translational modifications that alter their structural and functional properties. These reactions concern all proteins but especially tissue proteins (whose half-life in the organism can be several decades) and lead to the formation of complex products called PTMDPs ("post-translational modification derived products"). Molecular aging is responsible for the alteration of protein properties which may cause changes in mechanical properties of tissues during aging and pathologies. However, the involvement of these processes in vivo remains unclear, particularly in the aneurysmal pathology. So, the aim of this study is to determine whether the molecular aging of matrix proteins within the vessel wall may participate in the development of aortic aneurysm.

The investigators hypothesized that the molecular aging of matrix proteins may participate in the formation of aortic aneurysm. Indeed, it is well known that the aneurysm wall is subjected to important structural changes including variations in extracellular matrix composition. However, few studies have looked for a link between the molecular aging of matrix proteins and the formation of aneurysm. So, the aim of this study is to understand the role of protein molecular aging in this context. For that purpose, several approaches will be used to reach this aim: (1) To evaluate the degree of modification of matrix components at the aneurysmal wall by biological and histological studies (concentrations of PTMDPs (homocitrulline, carboxymethyllysine, pentosidine and MG-H1) and expression of RAGE) ; (2) To determine if there is a link between tissue concentrations of PTMDPs and the severity of the aneurysmal pathology ; (3) To compare concentrations of PTMDPs obtained at the aneurysmal wall with those obtained in skin and serum ; (4) To establish a link between concentrations of PTMDPs (in serum, skin and vascular wall), fragmentation of elastin and different haematological parameters potentially involved in the development of the pathology aneurysmal. Design of the study: single-center cross-sectional study. Population: 40 patients with aneurysm of the infra-renal abdominal aorta requiring surgical treatment by open surgery. Patients will be divided into 2 groups based on the size of the aneurysm (Group 1: 20 patients with aneurysm diameter of below 75 mm; Group 2: 20 patients with aneurysm diameter above 75 mm; patients a ruptured aneurysm can be included in both groups). Investigation scheme: after obtaining the inform consent of the patient, several samples or investigations will be done: blood (PTMDPs and hematological paramaters), measurement of skin autofluorescence (AGE-Reader), skin biopsy collection (2 to 3 mm wide and a few centimeters during the laparotomy), a biopsy of both aneurysmal and not aneurysmal aortic wall (from the abdominal aorta fragment usually resected part of the surgery and therefore being surgical waste) and collection of intra-aneurysmal and peri-thrombotic liquid (if available). Statistical analyses: (1) Description of data using mean and standard deviation for quantitative variables and percentage for qualitative variables. (2) Comparison of PTMDP concentrations between patient groups and between tissue locations (healthy or aortic aneurysms) using the Mann-Whitney test. (3) Search for links between concentrations of tissue PTMDPs, serum, skin autofluorescence, and hematologic markers using the Spearman correlation tests.