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Elevated Indices of Collagen Synthesis in Pulmonary Arterial Hypertension

Zeenat Safdar


Adaani Frost

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Conference: 2008 International PHA Conference and Scientific Sessions

Release Date: 06.20.2008

Presentation Type: Abstracts

Safdar Z., Frost. A.E. 

Baylor College of Medicine, Houston, TX, USA

BACKGROUND: Pulmonary Arterial Hypertension (PAH) is characterized by pulmonary arterial hypertrophy and increased collagen deposition.  In human studies, collagen production has been documented in small pulmonary arteries of subjects with severe PAH.  However, there is paucity of data regarding serological indices of collagen metabolism in PAH.  Our hypothesis was that serological indices of collagen synthesis would be elevated in PAH and these elevated levels would correlate with disease severity.

METHODS: After obtaining informed consent, we enrolled 12 PAH and 6 healthy subjects from the Baylor PH Center. Serum was separated by centrifugation and stored at -80 ºC refrigerator for analysis.  Type III procollagen (PIIINP), a marker of collagen I turnover, was measured by double antibody radioimmunoassay; type I procollagen carboxyterminal propeptide (PICP), a marker of collagen I synthesis, and carboxyterminal collagen type I peptide (ICTP), a marker of collagen I degradation, were determined by enzyme linked immunosorbent assay.  Demographics, six-minute walk distance, and echocardiographic data was collected by chart review. 

RESULTSOf the 12 PAH subjects, 6 had idiopathic PAH, 3 had congenital heart disease, 1 had anorexigen, and 1 had connective tissue disease associated PAH.  The mean circulating levels of the tested biomarkers in controls as compared to PAH subjects were respectively: PIIINP 2.68±0.37 µg/L and 4.18±0.37 µg/L (p=0.004), PICP 717±246 ng/mL and 804±412 ng/mL (p=0.219), and ICTP 2.04±0.84 ng/mL and 3.18±1.17 ng/mL (p=0.016).  The significantly increased PIIINP and ICTP in PAH suggest active collagen III turnover and collagen I degradation.  Correlating these biomarkers with parameters suggesting disease activity demonstrated a significant negative correlation between PIIINP and cardiac output (R= -0.77; p=0.009).  There was a trend toward a positive correlation between PIIINP level and right atrial pressure (R=0.51; p=0.10), and a negative correlation with six-minute walk distance (R= -0.32; p=0.33). The trends in these parameters however did not meet statistical significance. 

CONCLUSIONS: Our pilot study indicated that markers of collagen synthesis, PIIINP and ICTP, were elevated in PAH.  Elevated level of PIIINP, points to enhance active fibrosis, associated with lower cardiac output, higher right atrial pressure and reduced six-minute walk distance in PAH.  Markers of collagen synthesis may emerge as novel disease parameters that require further investigation.