title: Circulating biomarkers of collagen metabolism in arterial hypertension: relevance of target organ damage.
abstract: OBJECTIVE
  Increasing experimental evidence indicates that alterations in the extracellular matrix are implicated in hypertension and its chronic complications. Selected markers of extracellular matrix metabolism were investigated as potential biomarkers for hypertensive remodelling and correlated with the severity and extent of target organ damage (TOD) in patients with essential hypertension.
  
  
  METHODS
  We studied 159 consecutive patients being treated for essential hypertension. An exhaustive evaluation of the heart, kidney and blood vessel damage was performed, and plasma levels of plasma procollagen type I (PICP), matrix metalloproteinase-1 (MMP-1) and its inhibitor (tissue inhibitor metalloproteinase-1, TIMP-1) were determined. Patients were categorized into four groups: no TOD (33 patients), level 1 TOD (52 patients), level 2 TOD (44 patients) and level 3 TOD (30 patients).
  
  
  RESULTS
  The serum levels of MMP-1 and TIMP-1 were higher in patients with TOD than in hypertensive patients without TOD. Increasing levels of these molecules were progressively associated with an increase in the number of organs damaged, with highest levels of markers in patients with level 3 TOD (heart, kidney and blood vessels). There were no differences in PICP levels between groups. We found a slight but significant correlation between TIMP-1 and all hypertensive organ damage. Logistic regression analysis showed that age, smoking, diabetes mellitus, abdominal perimeter, MMP-1 and TIMP-1 were independently related to the level of TOD.
  
  
  CONCLUSIONS
  Circulating concentration of MMP-1 and TIMP-1 is associated with an extended hypertensive disease, with more TOD. TIMP-1 may have a role as a biomarker of total remodelling burden in hypertensive patients.
authors.affiliation: Arterial Hypertension Unit, Department of Cardiology, Hospital Universitario de San Juan, Spain. pedromorillas@teleline.es
authors.forename: Pedro
authors.initials: P
authors.lastname: Morillas
authors.forename: Juan
authors.initials: J
authors.lastname: Quiles
authors.forename: Helder
authors.initials: H
authors.lastname: de Andrade
authors.forename: Jesus
authors.initials: J
authors.lastname: Castillo
authors.forename: Estefanía
authors.initials: E
authors.lastname: Tarazón
authors.forename: Esther
authors.initials: E
authors.lastname: Roselló
authors.forename: Manuel
authors.initials: M
authors.lastname: Portolés
authors.forename: Miguel
authors.initials: M
authors.lastname: Rivera
authors.forename: Vicente
authors.initials: V
authors.lastname: Bertomeu-Martínez
mesh_terms: D000328:Adult; D000368:Aged; D055109:Ankle Brachial Index; D015415:Biomarkers / Q000097:blood* / Q000378:metabolism; D001795:Blood Pressure Determination; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D024042:Collagen Type I / Q000097:blood; D004452:Echocardiography; D000075222:Essential Hypertension; D005109:Extracellular Matrix / Q000473:pathology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000378:metabolism / Q000503:physiopathology*; D007674:Kidney Diseases / Q000097:blood; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood; D008875:Middle Aged; D012044:Regression Analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1