Potential mechanisms of the acute coronary syndrome presentation in patients with the coronary slow flow phenomenon - Insight from a plasma proteomic approach

Aims: The coronary slow flow phenomenon [CSFP] is a coronary microvascular disorder, characterized by delayed distal vessel opacification despite the absence of obstructive coronary artery disease. Patients frequently present with an acute coronary syndrome [ACS] although the pathophysiological mechanisms responsible are unknown. The aim of this study was to identify potential mechanisms for the ACS presentation associated with the CSFP using a plasma proteomic profiling approach. Methods and results: Plasma samples from nine CSFP subjects [56 +/- 11 years] were assayed for high sensitivity C-reactive protein [hsCRP], troponin T [TnT], creatine kinase [CK], and proteomic analyses (n=6), during an ACS presentation and one month later [chronic phase]. Proteomic analysis involved chromatographic depletion of abundant plasma proteins followed by two-dimensional differential gel electrophoresis [2-D DIGE]. Protein spots demonstrating +/- 1.5-fold change relative to the control were identified by mass spectrometry and two differentially expressed proteins were selected for validation via Western blotting. During the ACS presentation, hsCRP was elevated [ACS=14.9 +/- 3.9 mg/L vs chronic=4.23 +/- 1.37 mg/L, p=0.05] but TnT and CK levels were unchanged. Proteomic analysis identified six proteins that were significantly different in abundance between the acute and chronic samples. During the ACS presentation there was a 1.6 +/- 0.13 fold increase in the anti-oxidant enzyme paraoxonase-1 and an increase in inflammatory proteins alpha-1-antichymotrypsin [1.65 +/- 0.13 fold] and alpha-1-antitrypsin [2.5 +/- 0.34 fold]. The latter was confirmed by Western blotting [1.33 +/- 0.17 OD acute/chronic ratio, p=0.05]. Conclusion: The findings from this novel detailed approach, implicate an inflammatory/oxidative stress process in the pathogenesis of the ACS presentation associated with the CSFP. Future studies should further elucidate these mechanisms. (C) 2011 Elsevier Ireland Ltd. All rights reserved.