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

Kopetz, Victoria; Penno, Megan A. S.; Hoffmann, Peter; Wilson, David P.; Beltrame, John F.

doi:10.1016/j.ijcard.2011.09.014

Cited by 34 publications

(20 citation statements)

References 33 publications

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“…Data are presented in scatter plots as mean and SEM. Downloaded from http://ahajournals.org by on April 27, 2019 Likewise, ACT was elevated during the first days after an acute coronary syndrome, 32,33 and a persistent postoperative increase was noticed after coronary artery bypass grafting. 34 Apart from this important role of ACT as a modulator between inflammation and progression of HF by extracellular mechanisms, it may also have important intracellular effects.…”

Section: Discussionmentioning

confidence: 95%

Post-transcriptional Regulation of α-1-Antichymotrypsin by MicroRNA-137 in Chronic Heart Failure and Mechanical Support

Lok

Mil

Bovenschen

et al. 2013

Circ: Heart Failure

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There is substantial interest in applying proteomics to obtain better understanding of disease processes and to develop new biomarkers for diagnosis and early detection of cardiovascular diseases. 5,6 The purpose of the present study was to investigate proteomic changes in reverse remodeling during LVAD support. Because the degree of reverse remodeling is more pronounced in patients with nonischemic dilated cardiomyopathy (DCM), 7 we focused on this subset of patients. Recently, we found that levels of α-1-antichymotrypsin (ACT) expression decrease in myocardial tissue during pulsatile-LVAD support, which was detected by proteomics and confirmed by immunosorbent assays. 8 However, the molecular pathways regulating ACT expression in the heart were not explored.Clinically, pulsatile-LVAD support is being replaced by continuous-flow LVAD (cf-LVAD) support. Therefore, we performed proteomics in plasma and heart tissue of DCM Correspondence to Sjoukje Irene Lok, MD, University Medical Center Utrecht, Department of Cardiology, Huispostnummer H04.312, Postbus 85500, 3508 GA Utrecht, The Netherlands. E-mail s.lok@umcutrecht.nl Background-Better understanding of the molecular mechanisms of remodeling has become a major objective of heart failure (HF) research to stop or reverse its progression. Left ventricular assist devices (LVADs) are being used in patients with HF, leading to partial reverse remodeling. In the present study, proteomics identified significant changes in α-1-antichymotrypsin (ACT) levels during LVAD support. Moreover, the potential role of ACT in reverse remodeling was studied in detail. Methods and Results-Expression of ACT mRNA (quantitative-polymerase chain reaction) decreased significantly in post-LVAD myocardial tissue compared with pre-LVAD tissue (n=15; P<0.01). Immunohistochemistry revealed that ACT expression and localization changed during LVAD support. Circulating ACT levels were elevated in HF patients (n=18) as compared with healthy controls (n=6; P=0.001) and normalized by 6 months of LVAD support. Because increasing evidence implicates that microRNAs (miRs) are involved in myocardial disease processes, we also investigated whether ACT is post-transcriptionally regulated by miRs. Bioinformatics analysis pointed miR-137 as a potential regulator of ACT. The miR-137 expression is inversely correlated with ACT mRNA in myocardial tissue. Luciferase activity assays confirmed ACT as a direct target for miR-137, and in situ hybridization indicated that ACT and miR-137 were mainly localized in cardiomyocytes and stromal cells. Conclusions-High ACT plasma levels in HF normalized during LVAD support, which coincides with decreased ACT mRNA in heart tissue, whereas miR-137 levels increased. MiR-137 directly targeted ACT, thereby indicating that ACT and miR-137 play a role in the pathophysiology of HF and reverse remodeling during mechanical support. Delineating the role of miRs in post-transcriptional gene regulation offers new insight into the mechanisms by which the heart adapts to mechanical suppo...

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Section: Discussionmentioning

confidence: 95%

Post-transcriptional Regulation of α-1-Antichymotrypsin by MicroRNA-137 in Chronic Heart Failure and Mechanical Support

Lok

Mil

Bovenschen

et al. 2013

Circ: Heart Failure

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“…Current research indicates that the inflammatory‐oxidative stress mechanism plays a key role in the development of MNR . During myocardial ischaemia, the function of the oxygen free radical scavenging system is weakened or even disappears altogether.…”

Section: Discussionmentioning

confidence: 99%

Intracoronary application of nicorandil regulates the inflammatory response induced by percutaneous coronary intervention

Wang

et al. 2020

J Cellular Molecular Medi

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Intracoronary application of nicorandil can effectively reduce the myocardial no‐reflow (MNR) after percutaneous coronary intervention (PCI). We sought to investigate the mechanisms of nicorandil in preventing MNR, besides that of dilating the coronary microvasculature. A total of 60 patients undergoing PCI were enrolled and randomly divided into a nicorandil group and a control group. Before PCI, 2 mg of nicorandil or an equal volume of normal saline was injected into the coronary artery. Blood samples were collected before, 24 hours and 1 week after PCI and inflammatory cytokines were tested. In the control group, the expression of pro‐inflammatory cytokines was significantly increased, while the anti‐inflammatory cytokines were decreased 24 hours after PCI. In contrast, these changes were reversed in the nicorandil group, indicating that nicorandil regulated the inflammatory response induced by PCI. Then, proteomic analysis was performed to further elucidate the potential mechanisms. A total of 53 differentially expressed proteins (DEPs) were found 24 hours after PCI in the control group, and the changes of these relevant genes were reversed in the nicorandil group. These DEPs were significantly enriched in the inflammatory pathways. In conclusion, the intracoronary application of nicorandil before PCI can regulate the inflammatory responses induced by PCI, which might be an important mechanism of nicorandil in preventing MNR.

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“…Kopetz et al . suggested that there was an inflammatory and oxidative stress process in the pathogenesis of the ACS presentation associated with the CSFP [ 31 ]. The binding of oxidized low-density lipoprotein to LOX-1 reduces endothelial nitric oxide synthase (eNOS) expression and the intracellular concentration of nitric oxide in endothelial cells through increased production of superoxide and increases in matrix metalloproteinase-1, -3, -9 and collagenase activity [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Association between soluble lectin-like oxidized low-density lipoprotein receptor 1 levels and coronary slow flow phenomenon

Caglar

Özde

Bıyık

et al. 2016

aoms

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IntroductionThe coronary slow flow phenomenon (CSFP) has been associated with myocardial ischemia, myocardial infarction, life-threatening arrhythmias, sudden cardiac death and increased cardiovascular mortality similar to coronary artery disease (CAD). Possible underlying mechanisms of CSFP are endothelial dysfunction, chronic inflammation, microvascular dysfunction and diffuse atherosclerosis. Soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) seems to play an important role in the pathogenesis of atherosclerosis. We hypothesized that sLOX-1 might be associated with CSFP, and aimed to research the relationship between sLOX-1 and CSFP.Material and methodsForty patients with angiographically proven CSFP and 43 patients with a normal coronary flow pattern (NCFP) were included in this study. Coronary blood flow was measured according to the Thrombolysis In Myocardial Infarction (TIMI) frame count method. sLOX-1 levels were measured in all study subjects.ResultsSerum levels of sLOX-1 were significantly higher in the CSFP group than the NCFP group (1061.80 ±422.20 ng/ml vs. 500.043 ±282.97 ng/ml, p < 0.001, respectively). Multivariate logistic regression analysis including sLOX-1, MPV, GGT and uric acid levels revealed a significant association between sLOX-1 levels and CSFP (Exp (B)/OR: 1.006, 95% CI: 1.002–1.010, p = 0.001).ConclusionsThe present study demonstrated that serum sLOX-1 levels were significantly higher in patients with CSFP and there was a strong association between high sLOX-1 levels and CSFP. High serum sLOX-1 levels may have an important role in the pathogenesis of CSFP. Future studies are needed to confirm these results.

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

Cited by 34 publications

References 33 publications

Post-transcriptional Regulation of α-1-Antichymotrypsin by MicroRNA-137 in Chronic Heart Failure and Mechanical Support

Post-transcriptional Regulation of α-1-Antichymotrypsin by MicroRNA-137 in Chronic Heart Failure and Mechanical Support

Intracoronary application of nicorandil regulates the inflammatory response induced by percutaneous coronary intervention

Association between soluble lectin-like oxidized low-density lipoprotein receptor 1 levels and coronary slow flow phenomenon

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