Preliminary analysis of proteome alterations in non-aneurysmal, internal mammary artery tissue from patients with abdominal aortic aneurysms

Abstract

Objective: The pathogenesis of abdominal aortic aneurysms (AAA) involves a disturbed balance of breakdown and buildup of arterial proteins. We envision that individuals with AAA carry generalized arterial protein alterations either because of effects of genetically or environmental AAA risk factors or because of compensatory changes due to signaling molecules released from the affected aneurysmal tissue.

Approach: Protein extraction and quantitative proteome analysis by LC-MS/MS (liquid chromatography-mass spectrometry) was done on individual samples from the internal mammary artery from 11 individuals with AAA and 33 sex- and age-matched controls without AAA. Samples were selected from a biobank of leftover internal mammary arterial tissue gathered at coronary by-pass operations.

Results: We identified and quantitated 877 proteins, of which 44 were differentially expressed between the two groups (nominal p-values without correction for multiple testing). Some proteins related to the extracellular matrix displayed altered concentrations in the AAA group, particularly among elastin-related molecules [elastin, microfibrillar-associated protein 4 (MFAP4), lysyl oxidase]. In addition, several histones e.g. (e.g. HIST1H1E, HIST1H2BB) and other vascular cell proteins (e.g. versican, type VI collagen) were altered.

Conclusions: Our results support the notion that generalized alterations occur in the arterial tree in patients with AAA. Elastin-related proteins and histones seem to be part of such changes, however these preliminary results require replication in an independent set of specimens and validation by functional studies.

Fig 1. The relative amount of histones in patients with and without AAA.

Histone H2B type 1-J(A), histone H1.4 (B), histone H2B type 1-K (C), histone H3.3 (D), histone H4 (E), core histone macro-H2A.1 (F) and histone H1.0 (G). Data are presented as median, interquartile and range. ** indicates p<0.001, * indicates p<0.01 (without correction for multiple testing).

Fig 2. The relative amounts of elastin-related arterial proteins.

Elastin (A), MFAP4 (B), lysyl oxidase (C), fibrillin-1 (D), MFAP2 (E) and fibulin-1(F) in patients without abdominal aortic aneurysm (non-AAA) or with abdominal aortic aneurysm (AAA). Data are presented as median, interquartile and range * indicates p<0.05 (without correction for multiple testing).