Proteomic profiling of acute coronary thrombosis reveals a local decrease in pigment epithelium-derived factor in acute myocardial infarction

Abstract

Thrombotic occlusion of an epicardial coronary artery on the grounds of atherosclerotic plaque is considered the ultimate step in AMI (acute myocardial infarction). However, the precise pathophysiological mechanisms underlying acute coronary occlusion are not fully understood. We have analysed proteomic profiles of systemic plasma and plasma derived from the site of coronary plaque rupture of non-diabetic patients with STEMI (ST-segment elevation myocardial infarction). Label-free quantification of MS/MS (tandem MS) data revealed differential regulation of complement cascade components and a decrease in anti-thrombotic PEDF (pigment epithelium-derived factor) between CS (culprit site)-derived plasma and systemic plasma. PEDF, which is known to have a protective role in atherothrombosis, was relatively decreased at the CS, with a level of expression inverse to local MMP-9 (matrix metalloproteinase-9) activity. CS plasma displayed enhanced proteolytic activity towards PEDF. Proteomics of coronary thrombus aspirates indicate that PEDF processing is associated with coronary plaque rupture.

Prognostic value of culprit site neutrophils in acute coronary syndrome

“…These data suggest that CS neutrophil accumulation may be a surrogate for the magnitude of the local inflammatory response that impacts downstream myocardial recovery. This hypothesis is supported by our previously published data demonstrating a strong positive correlation of CS neutrophil counts with local matrix metalloproteinase‐9 activity . A recently published study underlines the pivotal role of activated neutrophils during AMI by demonstrating an association between neutrophil gelatinase–associated lipocalin and clinical outcome .…”

Novel Biomarker MicroRNAs for Subtyping of Acute Coronary Syndrome: A Bioinformatics Approach

“…Many interleukin (IL) factors were also reported in immune response pathways related to AMI such as IL-9 [47], IL-10 [48], IL-17 [49], IL-18 [50], and IL-33 [51]. In the development group, there were five pathways related to AMI, including WNT [52], G-CSF [53], SDF-1 [54], NF-kB [55], PEDF [56], and VEGF [57]. …”

Alteration of platelet GPVI signaling in ST-elevation myocardial infarction patients demonstrated by a combination of proteomic, biochemical, and functional approaches

“…Intracoronary samples from STEMI patients were taken during normal hemodynamics procedure using a Pronto V3 catheter (Vascular Solutions), which occludes antegrade flow allowing collecting culprit site blood from the distal artery252728. Peripheral arterial samples were obtained from the radial artery through which the sheath was inserted.…”