Acute ST-Segment Elevation Myocardial Infarction is Associated with Decreased Human Antimicrobial Peptide LL-37 and Increased Human Neutrophil Peptide-1 to 3 in Plasma

Zhao, Hanjun; Yan, Hong‐Bin; Yamashita, Shizuya; Li, Wenzheng; Liu, Chen; Chen, Yi; Zhou, Peng; Chi, Yunpeng; Wang, Shaoping; Zhao, Bo; Song, Li

doi:10.5551/jat.10108

Cited by 29 publications

(30 citation statements)

References 24 publications

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“…38 More recently, we demonstrated that HNP1-3 inhibits proteolytic cleavage of VWF by ADAMTS13. 11 Dramatic increases in plasma HNP1-3 are also reported in patients with myocardial infarction, 39,40 systemic lupus erythematosus, 41 and septic meningitis, 42 suggesting that HNP may also play a role in the pathogenesis of other inflammatory and thrombotic disorders. In TTP patients, we speculate that the massive release of HNP1-3 at the sites of vascular W. Cao et al 1324 haematologica | 2016; 101(11) Figure 4.…”

Section: Discussionmentioning

confidence: 99%

Human neutrophil peptides and complement factor Bb in pathogenesis of acquired thrombotic thrombocytopenic purpura

et al. 2016

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A cquired thrombotic thrombocytopenic purpura is primarily caused by the deficiency of plasma ADAMTS13 activity resulting from autoantibodies against ADAMTS13. However, ADAMTS13 deficiency alone is often not sufficient to cause acute thrombotic thrombocytopenic purpura. Infections or systemic inflammation may precede acute bursts of the disease, but the underlying mechanisms are not fully understood. Herein, 52 patients with acquired autoimmune thrombotic thrombocytopenic purpura and 30 blood donor controls were recruited for the study. The plasma levels of human neutrophil peptides 1-3 and complement activation fragments (i.e. Bb, iC3b, C4d, and sC5b-9) were determined by enzyme-linked immunosorbent assays. Univariate analyses were performed to determine the correlation between each biomarker and clinical outcomes. We found that the plasma levels of human neutrophil peptides 1-3 and Bb in patients with acute thrombotic thrombocytopenic purpura were significantly higher than those in the control (P<0.0001). The plasma levels of HNP1-3 correlated with the levels of plasma complement fragment Bb (rho=0.48, P=0.0004) and serum lactate dehydrogenase (rho=0.28, P=0.04); in addition, the plasma levels of Bb correlated with iC3b (rho=0.55, P<0.0001), sC5b-9 (rho=0.63, P<0.0001), serum creatinine (rho=0.42, p=0.0011), and lactate dehydrogenase (rho=0.40, P=0.0034), respectively. Moreover, the plasma levels of iC3b and sC5b-9 were correlated (rho=0.72, P<0.0001), despite no statistically significant difference of the two markers between thrombotic thrombocytopenic purpura patients and the control. We conclude that innate immunity, i.e. neutrophil and complement activation via the alternative pathway, may play a role in the pathogenesis of acute autoimmune thrombotic thrombocytopenic purpura, and a therapy targeted at these pathways may be considered in a subset of these patients.

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Section: Discussionmentioning

confidence: 99%

Human neutrophil peptides and complement factor Bb in pathogenesis of acquired thrombotic thrombocytopenic purpura

et al. 2016

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“…Levels of ␣-defensins in the plasma of Def ϩ/ϩ mice (74 Ϯ 11 g/liter) are comparable with plasma levels in healthy humans (15,18). We first asked whether ␣-defensins bind to LDL in Def ϩ/ϩ mice as we had observed in vitro (11).…”

Section: Endogenous ␣-Defensins Form Complexes With Plasma Ldlmentioning

confidence: 99%

“…Increased plasma levels of ␣-defensins are associated with acute myocardial infarction (15), cardiovascular mortality in patients with peripheral arterial disease (16), and chronic heart failure (17). ␣-Defensins stimulate foam cell formation (18), promote plaque instability (16), regulate aortic contractility, and acti-* This work was supported by National Institutes of Health Grants HL077760, HL805429, HL82545, and HL123912 and by Grant 930/04 from the Israeli Science Foundation.…”

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confidence: 99%

α-Defensins Induce a Post-translational Modification of Low Density Lipoprotein (LDL) That Promotes Atherosclerosis at Normal Levels of Plasma Cholesterol

Abu‐Fanne¹,

Maraga²,

Abd‐Elrahman

et al. 2016

Journal of Biological Chemistry

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Approximately one-half of the patients who develop clinical atherosclerosis have normal or only modest elevations in plasma lipids, indicating that additional mechanisms contribute to pathogenesis. In view of increasing evidence that inflammation contributes to atherogenesis, we studied the effect of human neutrophil ␣-defensins on low density lipoprotein (LDL) trafficking, metabolism, vascular deposition, and atherogenesis using transgenic mice expressing human ␣-defensins in their polymorphonuclear leukocytes (Def ؉/؉ ). Accelerated Def Atherosclerosis and its thrombotic sequel, "atherothrombosis," are likely to remain the predominant cause of death in "developed" countries for decades to come. The etiology of this syndrome is multifactorial, and current predictors provide an incomplete estimate of the risk and opportunity for intervention. In a pooled analysis of over 87,000 persons with diagnosed coronary heart disease, one in five lacked any of the conventional risk factors: hypertension, smoking, high cholesterol, or diabetes (1). Furthermore, half of all cardiovascular events occur in patients with normal lipid levels (2). These data reveal the need to identify and mitigate as yet undescribed, but clinically relevant, risk factors for cardiovascular disease beyond those targeted in current practice.This problem is compounded by the lack of animal models that closely simulate human disease. Animal models used to study atherosclerosis, including its hyperlipidemic (3, 4) and inflammatory (5) components, are often characterized by striking elevations in plasma cholesterol, reaching plasma concentrations of 1500 -2200 mg/dl in LDLR Ϫ/Ϫ and 400 -450 mg/dl in ApoE Ϫ/Ϫ mice fed a high fat diet (3, 4), and most of the cholesterol is found in the VLDL fraction (3, 4). Neither these levels of lipids nor this distribution of lipoproteins is representative of findings in the vast majority of patients with atherosclerosis. Thus, there continues to be a need for new models to identify novel risk factors and novel approaches to intervention.We have identified human ␣-defensins 1-4, also known as human neutrophil peptides (HNPs), 2 as potentially having a role in the development of atherosclerosis. ␣-Defensins are antimicrobial proteins that constitute ϳ5% of the total protein in polymorphonuclear leukocytes (PMNs). ␣-Defensins are released from a subset of azurophilic granules when the PMNs are activated by a variety of agonists (6, 7). ␣-Defensins are abundant in human atherosclerotic coronary and carotid arteries (8, 9), and there is a significant correlation between the deposition of ␣-defensins in skin tissue and the severity of coronary artery disease (10). ␣-Defensins inhibit the degradation of low density lipoprotein (LDL) and Lp(a) by vascular cells (11), increase their binding and retention in extracellular matrix (12), and inhibit tissue-type plasminogen activator (tPA)-mediated fibrinolysis (13, 14).These observations have been confirmed and extended by others. Increased plasma levels of ␣-defensins are assoc...

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“…Joseph et al reported higher plasma HNP levels in patients with type 1 diabetes with cardiovascular disease (CVD) than without CVD, and they indicate HNPs as a risk marker for CVD-related morbidity and mortality in diabetics [21]. Zhao et al noted the highest HNP1-3 levels in patients with acute ST elevation myocardial infarction compared with stable CAD and without CAD [22]. Their results suggest that HNP1-3 levels are chronically increased in stable CAD and rise even more in the acute state of myocardial infarction [22].…”

Section: Discussionmentioning

confidence: 99%

“…Zhao et al noted the highest HNP1-3 levels in patients with acute ST elevation myocardial infarction compared with stable CAD and without CAD [22]. Their results suggest that HNP1-3 levels are chronically increased in stable CAD and rise even more in the acute state of myocardial infarction [22]. Several studies have demonstrated that the severity of CAD is related to the WBC count [23, 24].…”

Section: Discussionmentioning

confidence: 99%

The correlation between plasma human neutrophil peptide 1-3 levels and severity of coronary artery disease

Ünğan¹,

Çağlar²,

Bıyık³

et al. 2016

Arch Med Sci Atheroscler Dis

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Introduction: Inflammation plays a key role in atherosclerosis, and discovering new biomarkers of inflammation is becoming important in order to uncover the pathogenesis of atherosclerotic coronary artery disease (CAD). Recent studies have focused on polymorphonuclear neutrophils. It has been suggested that human neutrophil peptide 1-3 (HNP1-3) is proatherogenic. In this study, we aimed to investigate the associations between plasma HNP1-3 levels and the severity of atherosclerosis via a generally accepted scoring system. Material and methods: This cross-sectional, observational study included 107 consecutive patients suffering from stable angina pectoris and undergoing coronary angiography (CAG). Patients were divided into two groups according to the Gensini scoring (GS) system evaluating disease severity. Group 1 was composed of mild CAD patients with GS < 20 and group 2 consisted of severe CAD patients with GS ≥ 20. Plasma HNP1-3 levels were assessed by the ELISA method. Results: The mean HNP1-3 levels were found to be lower in group 1 than group 2 (134.7 ng/ml vs. 147.5 ng/ml). HNP1-3 levels were significantly higher in the severe CAD group than the mild CAD group according to GS (p < 0.001). The results of multivariate logistic regression analysis revealed that only age > 62 years and HNP1-3 > 134 ng/ml were independent predictors of the severity of CAD after adjusting for gender, smoking, hypertension, hyperlipidemia, diabetes, family history of CAD and white blood cell count. In predicting the severity of CAD, the sensitivity and specificity of HNP1-3 were 83.9% (p < 0.001) and 58.8% (p < 0.001), respectively. Conclusions: This study revealed that the plasma levels of HNP1-3 were significantly higher in severe CAD than mild CAD.

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Acute ST-Segment Elevation Myocardial Infarction is Associated with Decreased Human Antimicrobial Peptide LL-37 and Increased Human Neutrophil Peptide-1 to 3 in Plasma

Cited by 29 publications

References 24 publications

Human neutrophil peptides and complement factor Bb in pathogenesis of acquired thrombotic thrombocytopenic purpura

Human neutrophil peptides and complement factor Bb in pathogenesis of acquired thrombotic thrombocytopenic purpura

α-Defensins Induce a Post-translational Modification of Low Density Lipoprotein (LDL) That Promotes Atherosclerosis at Normal Levels of Plasma Cholesterol

The correlation between plasma human neutrophil peptide 1-3 levels and severity of coronary artery disease

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