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

• Published in: International journal of cardiology Vol. 156; no. 1; pp. 84 - 91
• Main Authors: Kopetz, Victoria A., Penno, Megan A.S., Hoffmann, Peter, Wilson, David P., Beltrame, John F.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 05.04.2012; Elsevier
• Subjects: 2-D DIGE; Acute Coronary Syndrome - blood; Acute Coronary Syndrome - diagnosis; Acute Coronary Syndrome - epidemiology; Adult; Aged; Biological and medical sciences; Blood Proteins - metabolism; Cardiology. Vascular system; Cardiovascular; Coronary heart disease; Coronary slow flow; Female; Heart; Humans; Male; Medical sciences; Middle Aged; Myocarditis. Cardiomyopathies; No-Reflow Phenomenon - blood; No-Reflow Phenomenon - diagnosis; No-Reflow Phenomenon - epidemiology; Oxidative Stress; Prospective Studies; Proteomics; Proteomics - methods; Syndrome X; CSFP; 2D-DIGE; Coronary slow flow; 2-D DIGE; CK; CBG; ICAM-1; ACN; ACS; E-selectin; ACT; LRα2GP; VCAM-1; AAT; Proteomics; hsCRP; Syndrome X; TnT; FA; PON-1; leucine-rich alpha-2-glycoprotein; high-sensitivity C-reactive protein; troponin T; acute coronary syndrome; creatine kinase; acetonitrile; coronary slow flow phenomenon; formic acid; inter-cellular adhesion molecule; corticosteroid binding globulin; paraoxonase-1; endothelial selectin; alpha-1 anti-trypsin; two-dimensional difference gel electrophoresis; vascular cell adhesion molecule; alpha-1 anti-chymotrypsin; Human; Biological fluid; Coronary artery; Patient; Cardiovascular disease; Slow flow; Potential; Myocardial disease; Coronary heart disease; Mechanism; Blood plasma; Surgical approach; Cardiology; Acute coronary syndrome
• ISSN: 0167-5273; 1874-1754; 1874-1754
• DOI: 10.1016/j.ijcard.2011.09.014

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. Plasma samples from nine CSFP subjects [56±11years] 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±3.9mg/L vs chronic=4.23±1.37mg/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]. 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.