PURPOSE: Pulmonary arterial hypertension (PAH) is a disease of pulmonary arteries characterized by vasoconstriction and remodeling. This hypertrophic process involves synthesis of collagen and elastin.The objective of this study is to determine whether changes in pulmonary vascular structure are associated with increased elastin turnover by measuring two aminoacids specific for mature elastin, i.e. desmosine (D) and isodesmosine (I).
METHODS: PAH confirmed by right heart catheterization, included newly diagnosed patients or patients treated for no longer than three months. Exclusion criteria were age less than 18 years, evidence of left heart disease, COPD. Mass spectrometry (MS) was performed on plasma and 24 hour urine for detection of D and I. The control subjects were healthy non smokers. All the measurements were done in triplicates, average value +/- SD was used.
RESULTS: 13 PAH subjects were analyzed. Etiology of PAH included idiopathic PAH, associated with sickle cell disease , HIV , connective tissue disease , portopulmonary, chronic thromboembolic disease, congenital heart disease, sarcoidosis.The mean pulmonary arterial pressure (PAPm) ranged from 27 to 76 mm Hg, cardiac output 3.8 and 11.7 l/min. The mean levels of D and I measured in plasma of control subjects were 0.19 ng/mL and 3.53 ng/g protein, respectively. The levels of D and I in the plasma of patients with PAH were 0.52 ng/ml and 9.03 ng/g protein which were statistically higher that those found in control subjects (p= 0.0008). The mean levels of free and total D and I in the urine PAH patients was 11.25 mg/g creatinine and 22.26 mg/g creatinine respectively which were statistically higher than those in control subjects 2.52mg/g creatinine and 12.78mg/g creatinine urine (p<0.0001 and 0.0023).
CONCLUSION: Mass spectrometry allows a sensitive and specific analysis of desmosine and isodesmosine in patient's urine and plasma. Increased levels of these markers are detected in patients with PAH.
CLINICAL IMPLICATIONS: The results warrant further study to demonstrate that desmosine and isodesmosine may be used as biomarkers for early detection of the disease and responses to therapy.
DISCLOSURE: Ruth Minkin, No Financial Disclosure Information; No Product/Research Disclosure Information