title: Proteome analysis of human arterial tissue discloses associations between the vascular content of small leucine-rich repeat proteoglycans and pulse wave velocity.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: From the Department of Clinical Biochemistry and Pharmacology (M.L.H., H.C.B., P.S.J., L.M.R.), Centre of Individualized Medicine In Arterial Diseases (CIMA) (M.L.H., H.C.B., P.S.J., M.H.O., L.M.R.), Department of Cardiothoracic and Vascular Surgery (A.I.), Centre for Clinical Proteomics (H.C.B.), and The Cardiovascular and Metabolic Preventive Clinic, Department of Endocrinology Denmark (M.H.O.), Odense University Hospital, Odense, Denmark. maria.lyck.hansen@Rsyd.dk.
authors.forename: Maria
authors.initials: M
authors.lastname: Lyck Hansen
authors.affiliation: From the Department of Clinical Biochemistry and Pharmacology (M.L.H., H.C.B., P.S.J., L.M.R.), Centre of Individualized Medicine In Arterial Diseases (CIMA) (M.L.H., H.C.B., P.S.J., M.H.O., L.M.R.), Department of Cardiothoracic and Vascular Surgery (A.I.), Centre for Clinical Proteomics (H.C.B.), and The Cardiovascular and Metabolic Preventive Clinic, Department of Endocrinology Denmark (M.H.O.), Odense University Hospital, Odense, Denmark.
authors.forename: Hans Christian
authors.initials: HC
authors.lastname: Beck
authors.affiliation: From the Department of Clinical Biochemistry and Pharmacology (M.L.H., H.C.B., P.S.J., L.M.R.), Centre of Individualized Medicine In Arterial Diseases (CIMA) (M.L.H., H.C.B., P.S.J., M.H.O., L.M.R.), Department of Cardiothoracic and Vascular Surgery (A.I.), Centre for Clinical Proteomics (H.C.B.), and The Cardiovascular and Metabolic Preventive Clinic, Department of Endocrinology Denmark (M.H.O.), Odense University Hospital, Odense, Denmark.
authors.forename: Akhmadjon
authors.initials: A
authors.lastname: Irmukhamedov
authors.affiliation: From the Department of Clinical Biochemistry and Pharmacology (M.L.H., H.C.B., P.S.J., L.M.R.), Centre of Individualized Medicine In Arterial Diseases (CIMA) (M.L.H., H.C.B., P.S.J., M.H.O., L.M.R.), Department of Cardiothoracic and Vascular Surgery (A.I.), Centre for Clinical Proteomics (H.C.B.), and The Cardiovascular and Metabolic Preventive Clinic, Department of Endocrinology Denmark (M.H.O.), Odense University Hospital, Odense, Denmark.
authors.forename: Pia Søndergaard
authors.initials: PS
authors.lastname: Jensen
authors.affiliation: From the Department of Clinical Biochemistry and Pharmacology (M.L.H., H.C.B., P.S.J., L.M.R.), Centre of Individualized Medicine In Arterial Diseases (CIMA) (M.L.H., H.C.B., P.S.J., M.H.O., L.M.R.), Department of Cardiothoracic and Vascular Surgery (A.I.), Centre for Clinical Proteomics (H.C.B.), and The Cardiovascular and Metabolic Preventive Clinic, Department of Endocrinology Denmark (M.H.O.), Odense University Hospital, Odense, Denmark.
authors.forename: Michael Hecht
authors.initials: MH
authors.lastname: Olsen
authors.affiliation: From the Department of Clinical Biochemistry and Pharmacology (M.L.H., H.C.B., P.S.J., L.M.R.), Centre of Individualized Medicine In Arterial Diseases (CIMA) (M.L.H., H.C.B., P.S.J., M.H.O., L.M.R.), Department of Cardiothoracic and Vascular Surgery (A.I.), Centre for Clinical Proteomics (H.C.B.), and The Cardiovascular and Metabolic Preventive Clinic, Department of Endocrinology Denmark (M.H.O.), Odense University Hospital, Odense, Denmark.
authors.forename: Lars Melholt
authors.initials: LM
authors.lastname: Rasmussen
mesh_terms: D000368:Aged; D001011:Aorta / Q000503:physiopathology*; D015415:Biomarkers / Q000032:analysis; D002339:Carotid Arteries / Q000503:physiopathology*; D002853:Chromatography, Liquid; D003094:Collagen / Q000032:analysis; D005260:Female; D006801:Humans; D000090263:Leucine-Rich Repeat Proteins; D008297:Male; D008323:Mammary Arteries / Q000737:chemistry*; D008875:Middle Aged; D036103:Nanotechnology; D011506:Proteins / Q000032:analysis*; D011509:Proteoglycans / Q000032:analysis*; D040901:Proteomics / Q000379:methods; D063177:Pulse Wave Analysis; D053719:Tandem Mass Spectrometry; D059289:Vascular Stiffness
chemical_list: D015415:Biomarkers; D000090263:Leucine-Rich Repeat Proteins; D011506:Proteins; D011509:Proteoglycans; D003094:Collagen
keywords: extracellular matrix proteins; proteoglycans; proteomics; pulse wave analysis; vascular smooth muscle cells; vascular stiffness