Background: ST-elevation myocardial infarction (STEMI) is mostly caused by the rupture or the erosion of a vulnerable atherosclerotic plaque, initiating with intraluminal thrombosis and resulting in total occlusion of the coronary artery. Thrombus formation is a complex and dynamic process involving flow, blood cells and several plasma proteins, and it is still not completely understood. Purpose: To define - by proteomic profiling - the composition of occluding thrombus and its changes within time in patients with STEMI, trying to identify novel biomarkers of coronary thrombosis. Methods: We studied a consecutive series of 10 patients with STEMI, in which manual thrombus aspiration was successfully performed during primary percutaneous coronary intervention (PPCI). Thrombi were categorized by the elapsed time of onset-of-pain-to-PPCI in 2 groups: <3 hours (T1, n=5) and >3 hours (T2, n=5). Proteomic characterization was obtained by liquid chromatography coupled to mass spectrometry in LTQ-Orbitrap (LC-ESI-MS/MS). Results: Proteomic analysis identified a total of 717 proteins, of which 545 were equally expressed in the 2 groups, 53 were selectively expressed only in T1, 94 only in T2, 25 were co-expressed but with different modulation in the two groups. Proteins implicated in the coagulation cascade and platelet activation were more expressed in T1 than in T2, and included vitronectin (VTN), prothrombin (FII), protein-S (PROS1), factor V (FV), antithrombin III (ATIII), as well as proteins implicated in immunoregolatory functions, such as complement component 4 binding protein alpha (C4BPA), complement factor H (CFH), complement C3 (C3), HLA class I major histocompatibility antigen A-69 (HLA-A), major histocompability complex class I B (HLA-B) and plasma protease C1 inhibitor (SERPING1). At T2, defender against cell death 1 protein (DAD1), implicated in antiapoptotic process was found to be upregulated, similar to proteins implicated in redox reactions such as thioredoxin (TXN), haptoglobin (HP) and superoxide dismutase (SOD1).

Proteomic profiling of coronary thrombus in acute myocardial infarction

F Radico
;
D Pieragostino;C De Innocentiis;F Fulgenzi;M Ronci;I Cicalini;P Del Boccio;R De Caterina;
2018-01-01

Abstract

Background: ST-elevation myocardial infarction (STEMI) is mostly caused by the rupture or the erosion of a vulnerable atherosclerotic plaque, initiating with intraluminal thrombosis and resulting in total occlusion of the coronary artery. Thrombus formation is a complex and dynamic process involving flow, blood cells and several plasma proteins, and it is still not completely understood. Purpose: To define - by proteomic profiling - the composition of occluding thrombus and its changes within time in patients with STEMI, trying to identify novel biomarkers of coronary thrombosis. Methods: We studied a consecutive series of 10 patients with STEMI, in which manual thrombus aspiration was successfully performed during primary percutaneous coronary intervention (PPCI). Thrombi were categorized by the elapsed time of onset-of-pain-to-PPCI in 2 groups: <3 hours (T1, n=5) and >3 hours (T2, n=5). Proteomic characterization was obtained by liquid chromatography coupled to mass spectrometry in LTQ-Orbitrap (LC-ESI-MS/MS). Results: Proteomic analysis identified a total of 717 proteins, of which 545 were equally expressed in the 2 groups, 53 were selectively expressed only in T1, 94 only in T2, 25 were co-expressed but with different modulation in the two groups. Proteins implicated in the coagulation cascade and platelet activation were more expressed in T1 than in T2, and included vitronectin (VTN), prothrombin (FII), protein-S (PROS1), factor V (FV), antithrombin III (ATIII), as well as proteins implicated in immunoregolatory functions, such as complement component 4 binding protein alpha (C4BPA), complement factor H (CFH), complement C3 (C3), HLA class I major histocompatibility antigen A-69 (HLA-A), major histocompability complex class I B (HLA-B) and plasma protease C1 inhibitor (SERPING1). At T2, defender against cell death 1 protein (DAD1), implicated in antiapoptotic process was found to be upregulated, similar to proteins implicated in redox reactions such as thioredoxin (TXN), haptoglobin (HP) and superoxide dismutase (SOD1).
2018
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11564/697671
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