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: Ruth Minkin, Gagangeet Sandhu, Horiana Grosu, Lori Tartell, Shuren Ma, Yong Y Lin, Edward Eden, Gerard M Turino
• Journal: American journal of therapeutics (Am J Ther) 2017 Jul/Aug Vol. 24 Issue 4 Pg. e399-e404 ISSN: 1536-3686 [Electronic] United States
• PMID: 26237301 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Desmosine
• Elastin
• Isodesmosine

Topics

• Adult
• Aged
• Biomarkers (analysis)
• Chromatography, Liquid
• Delayed Diagnosis (prevention & control)
• Desmosine (analysis)
• Elastin (metabolism)
• Familial Primary Pulmonary Hypertension (blood, diagnosis, urine)
• Female
• Humans
• Isodesmosine (analysis)
• Male
• Mass Screening (methods)
• Middle Aged
• Pilot Projects
• Sputum (chemistry)
• Tandem Mass Spectrometry