Systemic scleroderma (SSc) is a chronic autoimmune disease characterized by early endothelial damage and collagen deposition in the skin and internal organs. In the lung, the diffuse (dSSc) and the limited (ISSc) subsets of SSc are characterized by pulmonary fibrosis (PF) and pulmonary hypertension (PH), respectively. The purpose of this study was to investigate: whether PCEB ACE dysfunction, an index of endothelial injury occurs in SSc, and whether it occurs prior to PH and/or PF development. Pulmonary capillary endotheliun-bound (PCEB) angiotensin converting enzyme (ACE) activity was estimated in eleven dSSc and six ISSc patients, as well as in nine adult volunteers (controls) with no lung disease, undergoing right heart catheterization for clinical purposes. By means of indicator-dilution techniques we measured the single pass transpulmonary hydrolysis of the synthetic ACE substrate ~3H-benzoyl-Phe-Ala-Pro (BPAP), expressed as % metabolism (%M) and v = -In(l-M), and calculated the modified kinetic parameter A_(max)/K_m, an index of functional capillary surface area (FCSA). Mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) were estimated in six dSSc, six ISSc patients and the nine volunteers. Pulmonary fibrosis was additionally estimated by high resolution comDuterized tomoeraDhv (CT) of the lune in sixteen SSc Datients.
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