Patients with microvascular obstruction after primary percutaneous coronary intervention show a gp91phox (NOX2) mediated persistent oxidative stress after reperfusion

Niccoli, Giampaolo; Celestini, Andrea; Calvieri, Camilla; Cosentino, Nicola; Falcioni, Elena; Carnevale, Roberto; Nocella, Cristina; Fracassi, Francesco; Roberto, Marco; Antonazzo, Roberta P; Pignatelli, Pasquale; Crea, Filippo; Violi, Francesco

doi:10.1177/2048872613504698

Cited by 18 publications

(9 citation statements)

References 40 publications

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“…Nox2-derived ROS are up-regulated in peripheral blood of STEMI patients [ 8 ] but the interplay with platelet activation at coronary site is still unclear.…”

Section: Introductionmentioning

confidence: 99%

Interplay between Oxidative Stress and Platelet Activation in Coronary Thrombus of STEMI Patients

et al. 2018

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Background: Platelet activation and oxidative stress seem to play a key role in coronary thrombus formation and are associated with thrombus burden in ST-elevation myocardial infarction (STEMI). However, the interplay between oxidative stress and platelet activation has not been fully elucidated. Materials and Methods: For 32 patients with STEMI undergoing primary percutaneous coronary intervention (PPCI) and 10 patients with stable angina (SA) and oxidative stress, as assessed by NADPH isoform 2 activity (soluble Nox2-derived peptide, sNox2-dp), levels of oxidized low-density lipoproteins (oxLDLs) and platelet activation markers such as soluble CD40 Ligand (sCD40L) and soluble P-selectin (sP-selectin) were measured in the retrieved material (coronary thrombi plus blood waste) of STEMI patients and in intracoronary blood of SA patients, respectively, and in peripheral blood samples of both groups. Results: In aspirated thrombi and blood waste of STEMI patients we found higher serum levels of sNox2-dp, oxLDLs, sCD40L, and sP-selectin, as compared to the intracoronary blood samples of SA patients. Moreover, in thrombi and blood waste of STEMI patients, a direct correlation between markers of oxidative stress and of platelet activation was found. Also, in STEMI patients a progressive increase of oxidative stress and platelet activation markers was observed according to the thrombus score burden. STEMI patients showed higher peripheral blood Nox2 activity and oxLDL levels as compared to SA patients. Conclusion: This study shows a close relationship between oxidative stress and platelet activation in the intracoronary blood waste and aspirated thrombi of STEMI patients, suggesting a role of oxidative stress in promoting thrombus formation and growth.

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“…Nox2-derived ROS are up-regulated in peripheral blood of STEMI patients [ 8 ] but the interplay with platelet activation at coronary site is still unclear.…”

Section: Introductionmentioning

confidence: 99%

Interplay between Oxidative Stress and Platelet Activation in Coronary Thrombus of STEMI Patients

et al. 2018

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“…Reperfusion strategies, such as thrombolysis, angioplasty, and percutaneous coronary intervention (PCI), when applied expeditiously, and coronary artery bypass grafting (CABG) can restore coronary flow and limit myocardial infarct size (IS), and reperfusion per se can paradoxically trigger irreversible tissue injury, namely, ischemia-reperfusion injury (IRI) which is regarded as an important contributor to the unsuccessful recovery after reperfusion therapy [ 5 , 6 ]. The increased reactive oxygen species (ROS) production during reperfusion and the subsequently increased oxidative damage are regarded as a pivotal factor contributing to the pathogenesis of IRI [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of Glucose Concentration on Propofol Cardioprotection against Myocardial Ischemia Reperfusion Injury in Isolated Rat Hearts

Yao

Tao

et al. 2015

Journal of Diabetes Research

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The anesthetic propofol confers cardioprotection against myocardial ischemia-reperfusion injury (IRI) by reducing reactive oxygen species (ROS). However, its cardioprotection on patients is inconsistent. Similarly, the beneficial effect of tight glycemic control during cardiac surgery in patients has recently been questioned. We postulated that low glucose (LG) may promote ROS formation through enhancing fatty acid (FA) oxidation and unmask propofol cardioprotection during IRI. Rat hearts were isolated and randomly assigned to be perfused with Krebs-Henseleit solution with glucose at 5.5 mM (LG) or 8 mM (G) in the absence or presence of propofol (5 μg/mL) or propofol plus trimetazidine (TMZ). Hearts were subjected to 35 minutes of ischemia followed by 60 minutes of reperfusion. Myocardial infarct size (IS) and cardiac CK-MB were significantly higher in LG than in G group (P < 0.05), associated with reduced left ventricular developed pressure and increases in postischemic cardiac contracture. Cardiac 15-F2t-isoprostane was higher, accompanied with higher cardiac lipid transporter CD36 protein expression in LG. Propofol reduced IS, improved cardiac function, and reduced CD36 in G but not in LG. TMZ facilitated propofol cardioprotection in LG. Therefore, isolated heart with low glucose lost sensitivity to propofol treatment through enhancing FA oxidation and TMZ supplementation restored the sensitivity to propofol.

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“…Oxidative stress has also been linked to the development of microvascular obstruction. Speci cally, sustained levels of NOX2, the catalytic subunit of NADPH oxidase that is released by platelet activation, result in a vicious cycle of platelet aggregate stabilization and thrombus growth that contributes to CNR [21] . Huczek et al found that patients with higher platelet reactivity assessed by PFA-100 had a signi cantly higher percentage of angiographic NRP [22] .…”

Section: Discussionmentioning

confidence: 99%

Circulating miR-660-5p is associated with the no-reflow phenomenon in patients with ST segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

zhang

Zhao

He³

2020

Preprint

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Background: The no-reflow phenomenon (NRP) is an important factor affecting the prognosis of patients with acute myocardial infarction undergoing primary percutaneous coronary intervention (PPCI). This study aims to investigate the association of circulating miR-660-5p with NRP in patients with ST segment elevation myocardial infarction (STEMI) undergoing PPCI.Methods: Consecutive patients diagnosed with anterior STEMI within 12 h of pain onset were included in the study; in these patients, coronary angiography confirmed that the infarct-related artery was the left anterior descending (LAD) artery. Angiographic NRP was defined as a final TIMI flow of 2 or a final TIMI flow of 3 with a myocardial blush grade (MBG) < 2. High miR-660-5p was defined as a value in the third tertile. The relationship of circulating miR-660-5p with NRP was assessed using Spearman correlation analysis and multiple logistic regression analysis.Results: Fifty-two eligible patients were finally included in this study (mean age: 56±12.4 years, >65 years: 53.8%, male: 76.9%, and mean BMI: 26.3±3.5). The incidence of NRP was 38.5%. Circulating miR-660-5p was significantly related to the mean platelet volume (MPV). Patients were divided into tertiles by miR-660-5p levels (Q1: ≤ 7.18, Q2: 7.18-11.31, Q3: > 11.31). Patients in the high microRNA-660-5p group had almost a 6-fold higher risk of NRP than those in the low microRNA-660-5p group [(odds ratio (OR)=5.68, 95% confidence interval (CI) 1.40-23.07, p=0.015). When analysed by tertiles, consistent trends of an increasing relative odds of NRP were reported (OR1 for Q2 VS. Q1: 1.25, 95% CI: 0.27-5.73, p=0.77; OR2 for Q3 VS. Q1: 5.96, 95% CI: 1.33-26.66, p=0.02), even after multivariable adjustment. Receiver operating characteristic curve analysis demonstrated that the microRNA-660-5p level of 10.17 was the best cut-off level to predict the incidence of the no-reflow phenomenon in patients undergoing primary percutaneous coronary intervention with an area under the curve (AUC) of 0.768 (95% CI: 0.636-0.890).Conclusion: Circulating miR-660-5p was significantly associated with NRP, and it may be a useful biomarker to predict the incidence of NRP in patients with STEMI undergoing PPCI.

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Patients with microvascular obstruction after primary percutaneous coronary intervention show a gp91phox (NOX2) mediated persistent oxidative stress after reperfusion

Cited by 18 publications

References 40 publications

Interplay between Oxidative Stress and Platelet Activation in Coronary Thrombus of STEMI Patients

Interplay between Oxidative Stress and Platelet Activation in Coronary Thrombus of STEMI Patients

Effects of Glucose Concentration on Propofol Cardioprotection against Myocardial Ischemia Reperfusion Injury in Isolated Rat Hearts

Circulating miR-660-5p is associated with the no-reflow phenomenon in patients with ST segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

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