SESSION TYPE: Pulmonary Hypertension II
PRESENTED ON: Monday, October 22, 2012 at 04:00 PM - 05:30 PM
PURPOSE: Pulmonary Arterial Hypertension (PAH) has a high mortality and is characterized by pulmonary vascular remodeling. Collagen metabolism is regulated by matrix metalloproteinases (MMPs) that influence vascular remodeling, and activity of MMPs is tightly regulated by tissue inhibitor of MMPs (TIMPs). Aim of this study was to determine circulating levels of MMP and TIMP in a cohort of PAH patients.
METHODS: After obtaining informed consent, 59 idiopathic, anorexigen and hereditary PAH subjects were prospectively enrolled from the Baylor Pulmonary Hypertension Center and 28 age- and gender-matched healthy controls were enrolled from Baylor Medicine Clinic. Serum was separated from peripheral venous blood samples, and stored at -80 degree C before undergoing simultaneous analysis. Serum MMP-9 and TIMP-1 were measured by 2-site sandwich ELISAs (R&D systems).
RESULTS: Age of the control subjects was 47.5±14 years (mean± SD) whereas age of the PAH subjects was 45±14 years (p=0.34). BSA was similar between the two groups (p=0.36). Six-minute walk distance (6MWD) was lower in the PAH group (403±102 meters vs 467±71 meters, p=0.005) whereas BNP levels were higher in the PAH group (121±182 pg/ml vs. 16.3±7 pg/ml, p=0.009). MMP-9 levels were elevated in the PAH group (p=0.001) and TIMP-1 levels were lower in the control group (p<0.001). There was no correlation between MMP-9 and TIMP-1 levels, and 6MWD, Borg Dyspnea Score and BNP levels; however there was a weak negative correlation between MMP-9 and TIMP-1 levels and cardiac index (-0.2; p=0.06).
CONCLUSIONS: In PAH patients, MMP-9 and TIMP-1 levels are elevated and may indicate worse disease.
CLINICAL IMPLICATIONS: Circulating collagen biomarkers may be helpful in supporting new diagnostic and therapeutic strategies in PAH.
DISCLOSURE: Zeenat Safdar: Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Gilead Sciences, United Therapeutics
will discuss the role of circulating markers of collagen metabolism (MMP and TIMPs) in this presentationBaylor College of Medicine, Houston, TX