Pulmonary capillary endothelial dysfunction in early systemic sclerosis

Objective. Pulmonary capillary endothelium-bound angiotensin-converting enz yme (PCEB-ACE) activity is a sensitive and quantifiable index of endothelia l function in vivo. Systemic sclerosis (SSc) is characterized by endothelia l damage and excess collagen formation, causing mainly pulmonary hypertensi on (PH) in the limited cutaneous SSc (IcSSc) subset and interstitial lung d isease 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 PI F. Methods. Applying indicator-dilution techniques, we measured single-pass tr anspulmonary hydrolysis and percent metabolism (%M) of a synthetic ACE subs trate and calculated functional capillary surface area (FCSA) in 25 SSc pat ients 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 patient s without PH, substrate hydrolysis and %M were decreased in patients with I cSSc and more profoundly in those with dcSSc; loss of FCSA normalized to bo dy surface area (FCSA/BSA) was observed in dcSSc, but not in IcSSc. High-re solution computed tomography of the lung, performed in all SSc patients, re vealed no correlation between substrate %M, hydrolysis, or FCSA/BSA and the degree of PIF; 5 dcSSc and 5 IcSSc patients with no detectable PIF exhibit ed decreases in hydrolysis and %M, while FCSA/BSA was decreased only in dcS Sc. Conclusion. Depression of PCEB-ACE activity, indicating pulmonary endotheli al dysfunction, occurs early in SSc, in the absence of PH or PIF, and is mo re pronounced, at this early pulmonary disease stage, in dcSSc than in IcSS c.