title: Pulmonary capillary endothelial dysfunction in early systemic sclerosis.
abstract: OBJECTIVE
  Pulmonary capillary endothelium-bound angiotensin-converting enzyme (PCEB-ACE) activity is a sensitive and quantifiable index of endothelial function in vivo. Systemic sclerosis (SSc) is characterized by endothelial damage and excess collagen formation, causing mainly pulmonary hypertension (PH) in the limited cutaneous SSc (lcSSc) subset and interstitial lung disease with pulmonary interstitial fibrosis (PIF) in the diffuse cutaneous SSc (dcSSc) subset. This study was undertaken to investigate the hypothesis that PCEB-ACE activity is reduced early in SSc, in the absence of PH or PIF.
  
  
  METHODS
  Applying indicator-dilution techniques, we measured single-pass transpulmonary hydrolysis and percent metabolism (%M) of a synthetic ACE substrate and calculated functional capillary surface area (FCSA) in 25 SSc patients and 11 controls. Substrate hydrolysis and %M reflect ACE activity per capillary; FCSA reflects ACE activity per vascular bed.
  
  
  RESULTS
  PCEB-ACE activity was decreased in both SSc subsets. Among patients without PH, substrate hydrolysis and %M were decreased in patients with lcSSc and more profoundly in those with dcSSc; loss of FCSA normalized to body surface area (FCSA/BSA) was observed in dcSSc, but not in lcSSc. High-resolution computed tomography of the lung, performed in all SSc patients, revealed no correlation between substrate %M, hydrolysis, or FCSA/BSA and the degree of PIF; 5 dcSSc and 5 lcSSc patients with no detectable PIF exhibited decreases in hydrolysis and %M, while FCSA/BSA was decreased only in dcSSc.
  
  
  CONCLUSIONS
  Depression of PCEB-ACE activity, indicating pulmonary endothelial dysfunction, occurs early in SSc, in the absence of PH or PIF, and is more pronounced, at this early pulmonary disease stage, in dcSSc than in lcSSc.
authors.affiliation: Department of Critical Care & Pulmonary Medicine, Evangelismos Hospital and University of Athens Medical School, Greece.
authors.forename: S E
authors.initials: SE
authors.lastname: Orfanos
authors.forename: E
authors.initials: E
authors.lastname: Psevdi
authors.forename: N
authors.initials: N
authors.lastname: Stratigis
authors.forename: D
authors.initials: D
authors.lastname: Langleben
authors.forename: J D
authors.initials: JD
authors.lastname: Catravas
authors.forename: M
authors.initials: M
authors.lastname: Kyriakidis
authors.forename: H M
authors.initials: HM
authors.lastname: Moutsopoulos
authors.forename: C
authors.initials: C
authors.lastname: Roussos
authors.forename: P G
authors.initials: PG
authors.lastname: Vlachoyiannopoulos
mesh_terms: D000328:Adult; D000368:Aged; D001784:Blood Gas Analysis; D002196:Capillaries / Q000166:cytology / Q000201:enzymology; D004730:Endothelium, Vascular / Q000201:enzymology* / Q000503:physiopathology; D005260:Female; D006400:Hematocrit; D006801:Humans; D006976:Hypertension, Pulmonary / Q000201:enzymology / Q000503:physiopathology; D008168:Lung / Q000098:blood supply* / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000201:enzymology / Q000503:physiopathology; D012595:Scleroderma, Systemic / Q000201:enzymology* / Q000503:physiopathology; D014057:Tomography, X-Ray Computed
chemical_list: D007703:Peptidyl-Dipeptidase A