Proteome Analysis of Human Arterial Tissue Discloses Associations Between the Vascular Content of Small Leucine-Rich Repeat Proteoglycans and Pulse Wave Velocity

Abstract

Objectives-We hypothesized that arterial stiffness is associated with changes in the arterial protein profile, particularly of extracellular matrix components. We aimed at determining differentially expressed proteins by quantitative proteome analysis in arterial tissue from patients with different degrees of arterial stiffness. Approach and Results-Arterial stiffness, assessed by carotid-femoral pulse wave velocity (PWV), central blood pressure and augmentation index by pulse wave analysis were measured the day before surgery in a group of patients undergoing coronary artery bypass grafting. Protein extracts of well-defined, homogenous, nonatherosclerotic individual samples of the left mammary artery from 10 of these patients with high PWV and 9 with low PWV were compared by quantitative proteome analysis, using tandem mass tag labeling and nano-liquid chromatography mass spectrometry/mass spectrometry. Of 418 quantified proteins, 28 were differentially expressed between the groups with high and low PWV (P<0.05). Three of 7 members of the extracellular matrix family of small leucine-rich repeat proteoglycans displayed significant differences between the 2 groups (P=0.0079; Fisher exact test). Three other ECM proteins were differentially regulated, that is, collagen, type VIII, α-1 and α-2 and collagen, type IV, α-1. Several proteins related to smooth muscle cell function and structure were also found in different amounts between the 2 groups. Conclusions-Changes in the arterial amounts of small leucine-rich proteoglycans, known to be involved in collagen fibrillogenesis, and of some nonfibrillar collagens in combination with alterations in proteins related to functions of the human arterial smooth muscle are associated with arterial stiffness, as determined by PWV. fibril organization and fibrillogenesis. 8 Mice knockout models for SLRPs display disorganized collagen fibril network and loses functions of the connective tissue and present with different disorders related to abnormal collagen fibril sizes and network, such as aortic dissection and rupture, skin fragility, joint laxity, and tendon weakness. 9,10 In this study, we hypothesized that patients with a high degree of arterial stiffness display a specific protein expression pattern different from patients with a normal low degree of arterial stiffness. We applied a quantitative proteomic approach to identify differentially expressed proteins in individual arterial tissue samples obtained from patients with high and low PWV. We investigate the internal mammary artery because this vessel has proven to be a suitable model artery for studies of generalized nonatherosclerotic arterial changes, that is, its matrix composition, endothelial function, and biochemistry reflect alterations in both the coronary and carotid arteries, as well as other features related to the arterial system. 11-13 MethodsMaterials and Methods are available in the online-only Data Supplement. ResultsBaseline patient characteristics are summarized in Table 1. There were no statistical d...

Vascular proteomics in metabolic and cardiovascular diseases

“…This is surprising, especially given the recent technological and methodological developments. Similar approaches have been utilized effectively in characterizing the composition of the ECMs of other normal and diseased tissues ; in addition to our studies of the ECM signatures in abdominal aortic aneurysm and aorta , Hansen and colleagues showed differential expression of a number of ECM proteins in the internal thoracic artery associated with arterial stiffness, as assessed by pulse wave velocity . The same group also found that levels of BM proteins were elevated in internal thoracic arteries of patients with type 2 diabetes mellitus .…”

The matrix proteins aggrecan and fibulin-1 play a key role in determining aortic stiffness

“…The extracellular matrix (ECM) plays a central role in both the age-related remodelling of the vessel wall and its response to hypertension or injury. As proteoglycans are key components of the ECM and hence wall stiffness 14 , we focused on ACAN and FBLN-1 amongst the hits from our discovery study. Aggrecan is a protein best understood from its role in joint cartilage where its domain structure and function has been extensively investigated; especially its contribution to the viscoelastic properties of cartilage 15 .…”

Abdominal Aortic Aneurysms Growth Is Associated With High Concentrations of Plasma Proteins in the Intraluminal Thrombus and Diseased Arterial Tissue

“…The partial Spearman rank correlations were adjusted for smoking and diabetes mellitus status and intervention-size. Fisher exact test was used to test whether the distribution of significant versus nonsignificant correlated plasma-, ECM-and cytoskeletal-proteins were random, as previously described in Preil et al 22,23 Statistics were performed using Microsoft Excel, STATA 13. …”