title: Desmosine and Isodesmosine as a Novel Biomarker for Pulmonary Arterial Hypertension: A Pilot Study.
abstract: Delayed diagnosis is common in patients with pulmonary arterial hypertension (PAH). Right-sided heart catheterization, the gold standard for diagnosis, is invasive and cannot be applied for routine screening. Some biomarkers have been looked into; however, due to the lack of a clear pathological mechanism linking the marker to PAH, the search for an ideal one is still ongoing. Elastin is a significant structural constituent of blood vessels. Its synthesis involves cross-linking of monomers by 2 amino acids, desmosine and isodesmosine (D&I). Being extremely stable, elastin undergoes little metabolic turnover in healthy individuals resulting in very low levels of D&I amino acids in the human plasma, urine, or sputum. We hypothesized that in PAH patients, the elastin turnover is high; which in turn should result in elevated levels of D&I in plasma and urine. Using mass spectrometry, plasma and urine levels of D&I were measured in 20 consecutive patients with PAH confirmed by cardiac catheterization. The levels were compared with 13 healthy controls. The mean level of total plasma D&I in patients with PAH was 0.47 ng/mL and in controls was 0.19 ng/mL (P = 0.001). The mean levels of total D&I in the urine of PAH patients was 20.55 mg/g creatinine and in controls was 12.78 mg/g creatinine (P = 0.005). The mean level of free D&I in the urine of PAH patients was 10.34 mg/g creatinine and in controls was 2.52 mg/g creatinine (P < 0.001). This is the first study highlighting that the serum and urine D&I has a potential to be a novel screening biomarker for patients with PAH. It paves the way for larger studies to analyze its role in assessing for disease severity and response to treatment.
authors.affiliation: Division of Pulmonary Critical Care and Sleep Medicine, Mount Sinai Roosevelt and Mount Sinai St. Luke's, New York, NY.
authors.forename: Ruth
authors.initials: R
authors.lastname: Minkin
authors.forename: Gagangeet
authors.initials: G
authors.lastname: Sandhu
authors.forename: Horiana
authors.initials: H
authors.lastname: Grosu
authors.forename: Lori
authors.initials: L
authors.lastname: Tartell
authors.forename: Shuren
authors.initials: S
authors.lastname: Ma
authors.forename: Yong Y
authors.initials: YY
authors.lastname: Lin
authors.forename: Edward
authors.initials: E
authors.lastname: Eden
authors.forename: Gerard M
authors.initials: GM
authors.lastname: Turino
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D002853:Chromatography, Liquid; D057210:Delayed Diagnosis / Q000517:prevention & control; D003895:Desmosine / Q000032:analysis*; D004549:Elastin / Q000378:metabolism*; D065627:Familial Primary Pulmonary Hypertension / Q000097:blood* / Q000175:diagnosis / Q000652:urine*; D005260:Female; D006801:Humans; D007524:Isodesmosine / Q000032:analysis*; D008297:Male; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D010865:Pilot Projects; D013183:Sputum / Q000737:chemistry; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers; D003895:Desmosine; D004549:Elastin; D007524:Isodesmosine