title: Matrix metalloproteinase 10 is associated with disease severity and mortality in patients with peripheral arterial disease.
abstract: OBJECTIVE
  Peripheral arterial disease (PAD) is associated with poor prognosis in terms of cardiovascular (CV) morbidity and mortality. Matrix metalloproteinases (MMPs) contribute to vascular remodeling by degrading extracellular matrix components and play a role in atherosclerosis as demonstrated for MMP-10 (stromelysin-2). This study analyzed MMP-10 levels in PAD patients according to disease severity and CV risk factors and evaluated the prognostic value of MMP-10 for CV events and mortality in lower limb arterial disease after a follow-up period of 2 years.
  
  
  METHODS
  MMP-10 was measured by enzyme-linked immunosorbent assay in 187 PAD patients and 200 sex-matched controls.
  
  
  RESULTS
  PAD patients presented with increased levels of MMP-10 (702 ± 326 pg/mL control vs 946 ± 473 pg/mL PAD; P < .001) and decreased levels of tissue inhibitor of matrix metalloproteinase 1 (312 ± 117 ng/mL control vs 235 ± 110 ng/mL PAD; P < .001) compared with controls. Among PAD patients, those with critical limb ischemia (n = 88) showed higher levels of MMP-10 (1086 ± 478 pg/mL vs 822 ± 436 pg/mL; P < .001) compared with those with intermittent claudication (n = 99), whereas the MMP-10/tissue inhibitor of matrix metalloproteinase 1 ratio remained similar. The univariate analysis showed an association between MMP-10, age (P = .015), hypertension (P = .021), and ankle-brachial index (P = .006) in PAD patients that remained significantly associated with PAD severity after adjustment for other CV risk factors. Patients with the highest MMP-10 tertile had an increased incidence of all-cause mortality and CV mortality (P < .03).
  
  
  CONCLUSIONS
  Our results suggest that MMP-10 is associated with severity and poor outcome in PAD.
authors.affiliation: Department of Vascular Surgery, Complejo Hospitalario de Navarra, Pamplona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Martinez-Aguilar
authors.affiliation: Laboratory of Atherothrombosis, Division of Cardiovascular Sciences, CIMA, University of Navarra, Pamplona, Spain.
authors.forename: Violeta
authors.initials: V
authors.lastname: Gomez-Rodriguez
authors.affiliation: Laboratory of Atherothrombosis, Division of Cardiovascular Sciences, CIMA, University of Navarra, Pamplona, Spain.
authors.forename: Josune
authors.initials: J
authors.lastname: Orbe
authors.affiliation: Laboratory of Atherothrombosis, Division of Cardiovascular Sciences, CIMA, University of Navarra, Pamplona, Spain.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Rodriguez
authors.affiliation: Department of Vascular Surgery, Complejo Hospitalario de Navarra, Pamplona, Spain.
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Fernández-Alonso
authors.affiliation: Laboratory of Atherothrombosis, Division of Cardiovascular Sciences, CIMA, University of Navarra, Pamplona, Spain. Electronic address: croncalm@unav.es.
authors.forename: Carmen
authors.initials: C
authors.lastname: Roncal
authors.affiliation: Laboratory of Atherothrombosis, Division of Cardiovascular Sciences, CIMA, University of Navarra, Pamplona, Spain; Hematology Service, University Clinic of Navarra, Pamplona, Spain.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Páramo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016638:Critical Illness; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007383:Intermittent Claudication / Q000097:blood / Q000175:diagnosis / Q000201:enzymology* / Q000401:mortality; D007511:Ischemia / Q000097:blood / Q000175:diagnosis / Q000201:enzymology* / Q000401:mortality; D053208:Kaplan-Meier Estimate; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D053506:Matrix Metalloproteinase 10 / Q000097:blood*; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000097:blood / Q000175:diagnosis / Q000201:enzymology* / Q000401:mortality; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood
chemical_list: D015415:Biomarkers; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C511770:MMP10 protein, human; D053506:Matrix Metalloproteinase 10