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

2012 ◽  
Vol 123 (2) ◽  
pp. 111-119 ◽  
Author(s):  
Klaus Distelmaier ◽  
Christopher Adlbrecht ◽  
Johannes Jakowitsch ◽  
Oswald Wagner ◽  
Christopher Gerner ◽  
...  

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.

2013 ◽  
Vol 34 (suppl 1) ◽  
pp. P2243-P2243
Author(s):  
H. D. Bas ◽  
K. Baser ◽  
S. Yilmaz ◽  
A. F. Tuncel ◽  
P. Dogan ◽  
...  

Circulation ◽  
2004 ◽  
Vol 110 (8) ◽  
pp. 928-933 ◽  
Author(s):  
Myeong-Ki Hong ◽  
Gary S. Mintz ◽  
Cheol Whan Lee ◽  
Young-Hak Kim ◽  
Seung-Whan Lee ◽  
...  

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 904
Author(s):  
Celestino Sardu ◽  
Nunzia D’Onofrio ◽  
Michele Torella ◽  
Michele Portoghese ◽  
Simone Mureddu ◽  
...  

Background and purpose: pericoronary fat over-inflammation might lead to the development and destabilization of coronary plaque in patients with pre-diabetes (PDM). Notably, pericoronary fat could over-express the sodium-glucose cotransporter 2 (SGLT2) and leptin, along with decreased sirtuin 6 (SIRT6) expression in PDM vs. normoglycemic (NG) patients undergoing coronary artery bypass grafting (CABG) for acute myocardial infarction (AMI). However, in the current study, we evaluated inflammatory markers, SGLT2, SIRT6, and leptin levels in pericoronary fat and, subsequently, 12-month prognosis comparing PDM to NG subjected to CABG for AMI. In addition, we evaluated in PDM patients the effects of metformin therapy on SIRT6 expression, leptin, and SGLT2 levels, and assessed its beneficial effect on nitrotyrosine and inflammatory cytokine levels. Methods: we studied AMI patients referred for CABG, divided into PDM and NG-patients. PDM patients were divided into never-metformin users and metformin users. Finally, we evaluated major adverse cardiac events (MACE) at a 12-month follow-up. Results: the MACE was 9.1% in all PDM and 3% in NG patients (p < 0.05). Metformin users presented a significantly lower MACE rate in PDM than never-metformin users (p < 0.05). PDM showed higher inflammatory cytokines, 3-nitrotyrosine levels, SGLT2, and leptin content, and decreased SIRT6 protein levels in pericoronary fat compared to NG-patients (p < 0.05). PDM never-metformin-users showed higher SGLT2 and leptin levels in pericoronary fat than current-metformin-users (p < 0.05). Conclusions: metformin therapy might ameliorate cardiovascular outcomes by reducing inflammatory parameters, SGLT2, and leptin levels, and finally improving SIRT6 levels in AMI-PDM patients treated with CABG.


Author(s):  
Kosei Terada ◽  
Takashi Kubo ◽  
Takeyoshi Kameyama ◽  
Yoshiki Matsuo ◽  
Yasushi Ino ◽  
...  

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Z Sheng ◽  
Y Tan ◽  
H Yan

Abstract Background Previous study have demonstrated that plasma trimethylamine N-oxide (TMAO) is associated with vulnerable plaque characteristics as assessed by optical coherence tomography (OCT) in patients with coronary artery disease. However, the relation between TMAO and the culprit plaque characteristics as assessed by OCT in patients with acute myocardial infarction (AMI) exhibiting plaque rupture at the site of the culprit stenosis is unknown. Objective To explore the relation between plasma TMAO and coronary culprit plaque characterization assessed by OCT in AMI patients exhibiting plaque rupture. Method We prospectively enrolled 90 AMI patients with plaque rupture identified by OCT and collected demographic data, risk factors, coronary angiography and OCT data, medical history and laboratory findings of all patients. Plasma TMAO levels were detected by stable isotope dilution liquid chromatography tandem mass spectrometry. Macrophage presence in coronary culprit plaque was quantified by normalized standard deviation (NSD). Result All patients were divided into two groups (high TMAO group and low TMAO group) according to the median plasma TMAO level (3.22uM). The culprit plaques in the high TMAO group exhibited a thinner fibrous cap thickness (60um [60–100um] versus 90um [70–110um], P=0.013]), higher frequency of thin-cap fibroatheroma (TCFA) (15.6% versus 55.6%, P<0.001), microvessel (24.4% versus 4.4%, P=0.014) and macrophage infiltration (66.7% versus 26.7%, P<0.001) compared with the low TMAO group. Moreover, the level of TMAO was significantly positively associated with NSD (Pearson's correlation coefficient: r=0.766, P<0.001). Conclusion Plasma TMAO levels are associated with coronary plaque vulnerability and inflammation in patients with AMI exhibiting plaque rupture. Acknowledgement/Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2016-I2M-1-009)


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