title: Serum and tissue biomarkers in aortic stenosis.
abstract: BACKGROUND
  Calcific aortic valve stenosis (CAVS) is seen in a large proportion of individuals over 60 years. It is an active process, influenced by lipid accumulation, mechanical stress, inflammation, and abnormal extracellular matrix turnover. Various biomarkers (BMs) are studied, as regards mechanisms, diagnosis and prognosis.
  
  
  METHODS
  In the calcified valves calcium deposition, elastin fragmentation and disorganization of cellular matrix were assessed, together with expression of OPN, OPG, osteocalcin (OCN) and RL2. We prospectively studied the following serum BMs in 60 patients with CAVS and compared them to 20 healthy controls, free from any cardiac disease: Matrix metalloproteinases (MMP) 2 and 9 and tissue inhibitor of metalloproteinase 1 (TIMP1), which regulate collagen turnover, inflammatory factors, i.e. tumor necrosis factor a (TNFa), interleukin 2 (IL2), transforming growth factor β1 (TGF-β1) which regulates fibrosis, fetuin-A (fet-A), osteopontin (OPN), osteoprotegerin (OPG), sclerostin (SOST), and relaxin-2 (RL2) which positively or negatively regulate calcification. Monocyte chemoattractant protein 1 (MCP-1) which regulates migration and infiltration of monocytes/macrophages was also studied as well as malondialdehyde (MDA) an oxidative marker.
  
  
  RESULTS
  Extent of tissue valve calcification (Alizarin Red stain) was negatively correlated with tissue elastin, and RL2, and positively correlated with tissue OCN and serum TIMP1 and MCP-1 and negatively with MMP9. Tissue OCN was positively correlated with OPN and negatively with the elastin. Tissue OPN was negatively correlated with elastin and OPG. Tissue OPN OPG and RL2 were not correlated with serum levels In the serum we found in patients statistically lower TIMP1, fet-A and RL2 levels, while all other BMs were higher compared to the healthy group. Positive correlations between SOST and IL2, OPG and MDA but negative with TNFa and OPN were found; also MMP9 was negatively correlated with TNFa and MCP-1 was negatively correlated with TIMP1.
  
  
  CONCLUSIONS
  We found that many BMs expressing calcification, collagen breakdown, or formation, and inflammation are increased in the valve tissue and in the serum of patients with CAVS as compared with healthy group. Our findings may give new insights towards diagnosis but also therapy. Thus antisclerostin, and antiflammatory agents could be tried for preventing aortic calcification progression.
authors.affiliation: Center of Clinical, Experimental Surgery, & Translation Research. Biomedical Research Foundation Academy of Athens (BRFAA), Soranou Efesiou 4 11527Athens, Greece.
authors.forename: Alkistis
authors.initials: A
authors.lastname: Kapelouzou
authors.affiliation: Department of Pathology, Onassis Cardiac Surgery Center, Avenue Sygrou 356 17674Athens, Greece.
authors.forename: Loukas
authors.initials: L
authors.lastname: Tsourelis
authors.affiliation: Department of Pathology, Onassis Cardiac Surgery Center, Avenue Sygrou 356 17674Athens, Greece.
authors.forename: Loukas
authors.initials: L
authors.lastname: Kaklamanis
authors.affiliation: Laboratory of Molecular Immunopathology and Istocompatibility Onassis Cardiac Surgery Center, Avenue Sygrou 356 17674Athens, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Degiannis
authors.affiliation: Department of Pathology, Onassis Cardiac Surgery Center, Avenue Sygrou 356 17674Athens, Greece.
authors.forename: Nektarios
authors.initials: N
authors.lastname: Kogerakis
authors.affiliation: Center of Clinical, Experimental Surgery, & Translation Research. Biomedical Research Foundation Academy of Athens (BRFAA), Soranou Efesiou 4 11527Athens, Greece.
authors.forename: Dennis V
authors.initials: DV
authors.lastname: Cokkinos
keywords: Sclerostin; aortic valve stenosis; biomarkers; calcification; relaxin-2