title: Abnormal circulating levels of metalloprotease 9 and its tissue inhibitor 1 in angiographically proven peripheral arterial disease: relationship to disease severity.
abstract: BACKGROUND
  Peripheral arterial disease (PAD) is associated with adaptive changes in the vascular and muscle extracellular matrix (ECM) in response to reduced blood flow. Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), are key modulators of ECM turnover. We hypothesized that patients with intermittent claudication (with low ankle-brachial blood pressure index, <0.8), and critical ischaemia would have raised circulating levels of MMP-9, TIMP-1 and TIMP-2 compared with healthy controls, reflecting an increase in proteolytic activity which may be related to ECM turnover in PAD.
  
  
  METHODS
  We studied 36 patients (23 males; 65 +/- 9 years) with intermittent claudication and 43 (25 males; 68 +/- 12) patients with critical ischaemia. All patients had angiographic evidence confirming significant PAD.
  
  
  RESULTS
  Circulating levels of MMP-9 and TIMP-1 were higher (both P < 0.0001) in the PAD patient groups compared with the controls. Patients with critical ischaemia had MMP-9 and TIMP-1 levels that were significantly higher than those with intermittent claudication. There were no differences in circulating TIMP-2 levels between patients and controls. There was a modest positive correlation between the white cell count (WCC) and MMP-9, both patients with intermittent claudication (Spearman, r = 0.398, P = 0.016) and critical ischaemia (r = 0.378, P = 0.014).
  
  
  CONCLUSIONS
  We demonstrate higher levels of circulating MMP-9 and TIMP-1 in patients with intermittent claudication and critical ischaemia. Circulating concentrations of both markers can be related to disease severity, being higher in critical ischaemia compared with levels in intermittent claudication.
authors.affiliation: University Department of Medicine, Haemostasis Thrombosis and Vascular Biology Unit, City Hospital, Birmingham, UK.
authors.forename: M H
authors.initials: MH
authors.lastname: Tayebjee
authors.forename: K T
authors.initials: KT
authors.lastname: Tan
authors.forename: R J
authors.initials: RJ
authors.lastname: MacFadyen
authors.forename: G Y H
authors.initials: GY
authors.lastname: Lip
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D007383:Intermittent Claudication / Q000097:blood / Q000150:complications; D007511:Ischemia / Q000097:blood / Q000150:complications; D007866:Leg / Q000098:blood supply; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D016491:Peripheral Vascular Diseases / Q000097:blood* / Q000150:complications; D012720:Severity of Illness Index; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
chemical_list: D008075:Lipoproteins, HDL; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9