Shortness of breath (a.k.a. dyspn(o)ea) is caused by a wide range of conditions including acute anxiety, asthma, several lung diseases and infections, and various forms of heart failure.  In a recent paper, Mebazaa et al. [PubMed] sought new serum markers that would specifically identify those patients whose labored breathing was due to heart failure.

The authors screened proteins in blood serum using an unbiased mass-spectrometric proteomics approach.  Encouragingly, they identified the B-type natriuretic peptide (BNP) – a widely-used marker for the assessment of heart failure.  However they also found that the sulfhydryl oxidase, QSOX1, was a potentially useful diagnostic biomarker for heart failure.  They state:   “ … we found a novel biomarker QSOX1 to be highly sensitive and specific for … diagnosis in patients with acute dyspnoea with a performance equaling the gold standard biomarkers BNP and NT-proBNP. We further demonstrate that the combination of QSOX1 and BNP markedly reduces false positives and exerts the best specificity for … diagnosis in patients with dyspnoea.”

They also write “We found that QSOX1 is unaffected by many of the factors that weaken the value of BNP, and the combination of BNP plus QSOX1 provided the best sensitivity and specificity for ADHF in patients with dyspnoea.”

So why are elevated serum levels of QSOX1 associated with heart disease? Good question!  The authors speculate that there might be a connection QSOX and the need to insert a disulfide bond in the BNP peptide.  However, in our opinion, the vigorous disulfide bond-generating activity of QSOX would likely make short work of the < nM levels of these BNP peptides that are found in sera.  Perhaps enhanced QSOX1 secretion accompanies the remodeling of the extracellular matrix associated with damage to heart muscle.  Whatever the explanation, the results of Mebazza et al. suggest that QSOX has the potential to be a useful diagnostic indicator for heart failure.

Addenda

Although not mentioned in Mebazaa et al., or in an associated commentary, the connection between the human growth factor Quiescin Q6 and the disulfide bond-forming enzyme, now known as QSOX, was made by Hoober et al. and by Benayoun et al.  The discovery of QSOX on this side of the pond is recounted in an earlier article in this series.

For a description of the use of QSOX1 as a potential biomarker for pancreatic cancer see this link, and for its overexpression in prostate cancer see this link.

We note that QSOX was originally described in blood serum by Nakao and coworkers.

Frequently, a failing left ventricle is signaled by pulmonary edema and shortness of breath.  For a schematic of the pumping heart see.