Utility of discovery approach using proteomics to create a biomarker profile for coronary microvascular dysfunction

Coronary microvascular dysfunction (CMD) is a complex disease, difficult to diagnose and often requires advanced imaging. We used mass spectrometry (MS) using discovery approach to search for serum proteins as potential biomarkers in these patients.

We used serum samples from 10 patients with CMD and 10 with normal coronary flow reserve (CFR) admitted to an observation unit where acute myocardial infarction was excluded. We identified CMD using ⁸²Rb positron emission tomography/computed tomography as CFR <2 in response to regadenoson, in the absence of coronary calcification or regional perfusion defects. We used MS to identify potential protein biomarkers that were differentially expressed in cases and controls.

Baseline characteristics were not different between cases and controls, except for beta-blocker use and which was higher in cases, and mean (SD) CFR which was lower in cases [1.19 (0.23) and 2.78 (0.78) in cases and controls respectively; p < 0.01]. We identified 5345 peptides corresponding to 209 proteins, and identified 197 proteins by peptides with suitable properties to infer relative quantitation values. While the calculated values for some proteins (e.g. vascular cell adhesion molecule-1, apolipoprotein C and Von Willebrand Factor) indicate fold-differences between groups, these are most likely a result of high values in only 1-2 patients and are not statistically significant.

Mass spectrometry using discovery approach may not be an adequate method for quantitative assessment of serum proteins in CMD patients. Future MS studies should evaluate other approaches including tissue samples or serial measurements.