Cardiac-derived neutrophil chemotactic factors: Detection in coronary sinus effluents of patients undergoing myocardial revascularization

Elgebaly, Salwa A.; Hashmi, Furqan K.; Houser, Stuart L.; Allam, Medhat; Doyle, Kathleen

doi:10.1016/s0022-5223(19)34920-7

Cited by 30 publications

(9 citation statements)

References 25 publications

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“…Many researches showed that neutrophil infiltration and the release of inflammatory cytokines are 2 key contributors to myocardial I/R injury [ 35 , 36 ]. The early reperfusion period is characterized by a burst of infiltration of larger populations of neutrophils and monocytes/macrophages [ 37 , 38 ]. The accumulation of neutrophils is mediated by special adhesion molecules released from the vascular endothelium.…”

Section: Evaluation Of Hypothesismentioning

confidence: 99%

Effect of Hexadecyl Azelaoyl Phosphatidylcholine on Cardiomyocyte Apoptosis in Myocardial Ischemia-Reperfusion Injury: A Hypothesis

et al. 2018

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Reperfusion after myocardial ischemia can induce cardiomyocyte death, known as myocardial reperfusion injury. The pathophysiology of the process of reperfusion suggests the confluence multiple pathways. Recent studies have focused on the inflammatory response, which is considered to be the main mechanism during the process of myocardial ischemia-reperfusion injury and can cause cardiomyocyte apoptosis. Peroxisome proliferator-activated receptors gamma activated by endogenous ligands and exogenous ligand can decrease the inflammatory response in cardiomyocytes. Thiazolidinediones are synthetic, high-affinity, selective ligands for peroxisome proliferator-activated receptors gamma, and can inhibit the inflammatory response, decrease myocardial infarct size, and protect cardiac function. However, thiazolidinediones, including rosiglitazone and pioglitazone, can also contribute to adverse cardiovascular events such as congestive heart failure. Therefore, there are some limitations to the use of thiazolidinediones. Most endogenous ligands were of low affinity until hexadecyl azelaoyl phosphatidylcholine was identified as a high-affinity ligand and agonist for peroxisome proliferator-activated receptors gamma. Hexadecyl azelaoyl phosphatidylcholine binds recombinant peroxisome proliferator-activated receptors with an affinity (Kd(app) ≈40 nM) which is equivalent to rosiglitazone. Therefore, hexadecyl azelaoyl phosphatidylcholine is a specific peroxisome proliferator-activated receptors gamma agonist. Given these findings, we hypothesized that the use of hexadecyl azelaoyl phosphatidylcholine can activate the peroxisome proliferator-activated receptors gamma signal pathways and prevent the inflammatory response process of myocardial ischemia-reperfusion injury, with reduced cardiomyocyte apoptosis and death.

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Section: Evaluation Of Hypothesismentioning

confidence: 99%

Effect of Hexadecyl Azelaoyl Phosphatidylcholine on Cardiomyocyte Apoptosis in Myocardial Ischemia-Reperfusion Injury: A Hypothesis

et al. 2018

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“…Elgebaly et al [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ] reported that Nourin is a potent inflammatory mediator rapidly released by human and animal hearts in response to reversible ischemic injury and necrosis. Nourin is a 3-KDa N-formyl peptide and its release by ischemic cardiac tissue is associated with post-ischemic cardiac inflammation in early ischemia/reperfusion animal models of cardiopulmonary bypass surgery and acute myocardial infarction (AMI) [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Nourin-Associated miRNAs: Novel Inflammatory Monitoring Markers for Cyclocreatine Phosphate Therapy in Heart Failure

Elgebaly

Todd²,

Kreutzer

et al. 2021

IJMS

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Background: Cyclocreatine phosphate (CCrP) is a potent bioenergetic cardioprotective compound known to preserve high levels of cellular adenosine triphosphate during ischemia. Using the standard Isoproterenol (ISO) rat model of heart failure (HF), we recently demonstrated that the administration of CCrP prevented the development of HF by markedly reducing cardiac remodeling (fibrosis and collagen deposition) and maintaining normal ejection fraction and heart weight, as well as physical activity. The novel inflammatory mediator, Nourin is a 3-KDa formyl peptide rapidly released by ischemic myocardium and is associated with post-ischemic cardiac inflammation. We reported that the Nourin-associated miR-137 (marker of cell damage) and miR-106b-5p (marker of inflammation) are significantly upregulated in unstable angina patients and patients with acute myocardial infarction, but not in healthy subjects. Objectives: To test the hypothesis that Nourin-associated miR-137 and miR-106b-5p are upregulated in ISO-induced “HF rats” and that the administration of CCrP prevents myocardial injury (MI) and reduces Nourin gene expression in “non-HF rats”. Methods: 25 male Wistar rats (180–220 g) were used: ISO/saline (n = 6), ISO/CCrP (0.8 g/kg/day) (n = 5), control/saline (n = 5), and control/CCrP (0.8 g/kg/day) (n = 4). In a limited study, CCrP at a lower dose of 0.4 g/kg/day (n = 3) and a higher dose of 1.2 g/kg/day (n = 2) were also tested. The Rats were injected SC with ISO for two consecutive days at doses of 85 and 170 mg/kg/day, respectively, then allowed to survive for an additional two weeks. CCrP and saline were injected IP (1 mL) 24 h and 1 h before first ISO administration, then daily for two weeks. Serum CK-MB (U/L) was measured 24 h after the second ISO injection to confirm myocardial injury. After 14 days, gene expression levels of miR-137 and miR-106b-5p were measured in serum samples using quantitative real-time PCR (qPCR). Results: While high levels of CK-MB were detected after 24 h in the ISO/saline rats indicative of MI, the ISO/CCrP rats showed normal CK-MB levels, supporting prevention of MI by CCrP. After 14 days, gene expression profiles showed significant upregulation of miR-137 and miR-106b-5p by 8.6-fold and 8.7-fold increase, respectively, in the ISO/saline rats, “HF rats,” compared to the control/saline group. On the contrary, CCrP treatment at 0.8 g/kg/day markedly reduced gene expression of miR-137 by 75% and of miR-106b-5p by 44% in the ISO/CCrP rats, “non-HF rats,” compared to the ISO/Saline rats, “HF rats.” Additionally, healthy rats treated with CCrP for 14 days showed no toxicity in heart, liver, and renal function. Conclusions: Results suggest a role of Nourin-associated miR-137 and miR-106b-5p in the pathogenesis of HF and that CCrP treatment prevented ischemic injury in “non-HF rats” and significantly reduced Nourin gene expression levels in a dose–response manner. The Nourin gene-based mRNAs may, therefore, potentially be used as monitoring markers of drug therapy response in HF, and CCrP—as a novel preventive therapy of HF due to ischemia.

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“…Nourin is a novel blood biomarker with a known mode of action as an early potent inflammatory mediator released within 5 min by ischemic myocardial tissue and it is associated with the initiation and amplification of post-ischemic cardiac inflammation [10][11][12][13][14][15]. Clinically high levels of Nourin were detected in ACS and AMI patients, but not in symptomatic noncardiac patients and healthy subjects [17], suggesting a potential use of the Nourin biomarker to rule out myocardial ischemia for symptomatic patients having noncardiac causes.…”

Section: Discussionmentioning

confidence: 99%

“…Elgebaly et al [10][11][12][13][14][15] reported that Nourin is a 3 KDa formyl peptide that is released within five minutes by human and animal hearts in response to ischemic injury. Nourin is unique because of its rapid release by reversible ischemic myocardium when cells are initially injured, but still alive and not dead.…”

Section: Introductionmentioning

confidence: 99%

“…In our earlier publications, Nourin was referred to as cardiac-derived leukocyte chemotactic factor. Nourin was purified from cardioplegic solutions collected during cardiac arrest (reversible myocardial ischemia) from cardiopulmonary bypass patients when they underwent coronary revascularization [11], and its amino acid sequence was determined. As a formyl peptide, Nourin binds to formyl peptide receptor (FPR) on leukocytes and vascular endothelial cells (VECs).…”

Section: Introductionmentioning

confidence: 99%

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Nourin-Dependent miR-137 and miR-106b: Novel Early Inflammatory Diagnostic Biomarkers for Unstable Angina Patients

et al. 2021

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Background: Currently, no blood biomarkers exist that can diagnose unstable angina (UA) patients. Nourin is an early inflammatory mediator rapidly released within 5 min by reversible ischemic myocardium, and if ischemia persists, it is also released by necrosis. Nourin is elevated in acute coronary syndrome (ACS) patients but not in symptomatic noncardiac and healthy subjects. Recently, circulating microRNAs (miRNAs) have been established as markers of disease, including cardiac injury and inflammation. Objectives: To profile and validate the potential diagnostic value of Nourin-dependent miR-137 (marker of cell damage) and miR-106b-5p (marker of inflammation) as early biomarkers in suspected UA patients and to investigate the association of their target and regulating genes. Methods: Using Nourin amino acid sequence, an integrated bioinformatics analysis was conducted. Analysis indicated that Nourin is a direct target for miR-137 and miR-106b-5p in myocardial ischemic injury. Two linked molecular networks of lncRNA/miRNAs/mRNAs were also retrieved, including CTB89H12.4/miR-137/FTHL-17 and CTB89H12.4/miR-106b-5p/ANAPC11. Gene expression profiling was assessed in serum samples collected at presentation to an emergency department (ED) from: (1) UA patients (n = 30) (confirmed by invasive coronary angiography with stenosis greater than 50% and troponin level below the clinical decision limit); (2) patients with acute ST elevation myocardial infarction (STEMI) (n = 16) (confirmed by persistent ST-segment changes and elevated troponin level); and 3) healthy subjects (n = 16). Results: Gene expression profiles showed that miR-137 and miR-106b-5p were significantly upregulated by 1382-fold and 192-fold in UA compared to healthy, and by 2.5-fold and 4.6-fold in STEMI compared to UA, respectively. Healthy subjects showed minimal expression profile. Receiver operator characteristics (ROC) analysis revealed that the two miRNAs were sensitive and specific biomarkers for assessment of UA and STEMI patients. Additionally, Spearman’s correlation analysis revealed a significant association of miRNAs with the associated mRNA targets and the regulating lncRNA. Conclusions: Nourin-dependent gene expression of miR-137 and miR-106b-5p are novel blood-based biomarkers that can diagnose UA and STEMI patients at presentation and stratify severity of myocardial ischemia, with higher expression in STEMI compared to UA. Early diagnosis of suspected UA patients using the novel Nourin biomarkers is key for initiating guideline-based therapy that improves patients’ health outcomes.

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Cardiac-derived neutrophil chemotactic factors: Detection in coronary sinus effluents of patients undergoing myocardial revascularization

Cited by 30 publications

References 25 publications

Effect of Hexadecyl Azelaoyl Phosphatidylcholine on Cardiomyocyte Apoptosis in Myocardial Ischemia-Reperfusion Injury: A Hypothesis

Effect of Hexadecyl Azelaoyl Phosphatidylcholine on Cardiomyocyte Apoptosis in Myocardial Ischemia-Reperfusion Injury: A Hypothesis

Nourin-Associated miRNAs: Novel Inflammatory Monitoring Markers for Cyclocreatine Phosphate Therapy in Heart Failure

Nourin-Dependent miR-137 and miR-106b: Novel Early Inflammatory Diagnostic Biomarkers for Unstable Angina Patients

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