Netrin-1 is associated with macrophage infiltration and polarization in human epicardial adipose tissue in coronary artery disease

Gürses, Kadri Murat; Özmen, Füsun; Koçyiğit, Duygu; Yersal, Nilgün; Bilgiç, Elif; Kaya, Erkan; Köprü, Çağla Zübeyde; Soyal, Tolga; Doğancı, Suat; Tokgözoğlu, Lâle; Korkusuz, Petek

doi:10.1016/j.jjcc.2016.08.016

Cited by 22 publications

(17 citation statements)

References 28 publications

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“…Moreover, when we study the distribution of macrophage subtypes, our study shows that only CD11c and CD11c/CD68 ratio (M1-macrophage phenotypes), but not CD206 , were more significantly overexpressed in IHD-T2DM patients when compared to IHD-NDM or control group. In agreement with our findings, Gurses et al [16] observed a shift to pro-inflammatory M1-macrophage phenotype in EAT of patients with coronary artery disease (CAD) compared to the control group (without CAD), reflected by increased of CD11c , CD11c/CD68 and CD11c/CD206 ratios, but not CD206 . According to our results, Hirata et al [17] showed similar results, demonstrated that pro-inflammatory macrophages are more dominant in EAT when compared with and without CAD patients.…”

Section: Discussionsupporting

confidence: 93%

“…With respect to the macrophage infiltration, our work has shown that mRNA expression of CD68 was increased in EAT in patients with IHD and T2DM when compared with patients without T2DM and control group. In this sense, there are studies that have shown an increase in macrophage infiltration in the EAT of CAD patients, reflected by increased CD68 macrophage infiltration [16, 17]. In recent years, several studies have indicated that insulin resistance and T2DM are associated with the inflammation of adipose tissue [42–44].…”

Section: Discussionmentioning

confidence: 99%

“…An altered EAT is able locally to produce reactive oxygen species, cytokines and chemokines which may create a local toxic and proinflammatory environment [13–15]. The inflammation of EAT has been linked to IHD pathophysiology, which can be reflected by increased of macrophage infiltration [16, 17]. In this state, EAT shows a high infiltration of leukocytes [18], specifically T lymphocytes and macrophages [18, 19] and inflammatory cytokines [20].…”

Section: Introductionmentioning

confidence: 99%

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Overexpression of scavenger receptor and infiltration of macrophage in epicardial adipose tissue of patients with ischemic heart disease and diabetes

et al. 2019

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BackgroundOxidized low-density lipoproteins and scavenger receptors (SRs) play an important role in the formation and development of atherosclerotic plaques. However, little is known about their presence in epicardial adipose tissue (EAT). The objective of the study was to evaluate the mRNA expression of different SRs in EAT of patients with ischemic heart disease (IHD), stratifying by diabetes status and its association with clinical and biochemical variables.MethodsWe analyzed the mRNA expression of SRs (LOX-1, MSR1, CXCL16, CD36 and CL-P1) and macrophage markers (CD68, CD11c and CD206) in EAT from 45 patients with IHD (23 with type 2 diabetes mellitus (T2DM) and 22 without T2DM) and 23 controls without IHD or T2DM.ResultsLOX-1, CL-P1, CD68 and CD11c mRNA expression were significantly higher in diabetic patients with IHD when compared with those without T2DM and control patients. MSR1, CXCL16, CD36 and CD206 showed no significant differences. In IHD patients, LOX-1 (OR 2.9; 95% CI 1.6–6.7; P = 0.019) and CD68 mRNA expression (OR 1.7; 95% CI 0.98–4.5; P = 0.049) were identified as independent risk factors associated with T2DM. Glucose and glycated hemoglobin were also shown to be risk factors.ConclusionsSRs mRNA expression is found in EAT. LOX-1 and CD68 and were higher in IHD patients with T2DM and were identified as a cardiovascular risk factor of T2DM. This study suggests the importance of EAT in coronary atherosclerosis among patients with T2DM.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Overexpression of scavenger receptor and infiltration of macrophage in epicardial adipose tissue of patients with ischemic heart disease and diabetes

et al. 2019

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“…There is growing evidence supporting that the presence and severity of the cardiovascular disease can be detected using certain biomarkers and components of the lipid profile. However, to our knowledge, this is the first study that has reported the association among LCI ≥16, RBP and ACS [14][15][16].…”

Section: Discussionmentioning

confidence: 78%

The correlation of retinol-binding protein-4 and lipoprotein combine index with the prevalence and diagnosis of acute coronary syndrome

Liu

Han

et al. 2020

Heart Vessels

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Retinol-binding protein-4 (RBP-4) along with the lipid profile plays crucial roles in Acute coronary syndrome (ACS). The study aimed to investigate the correlation of RBP-4, lipoprotein combine index (LCI), and RBP-4 + LCI with ACS. 163 ACS and 77 non-CAD in patients were consecutively enrolled in this study. The serum level of RBP-4 was measured via enzyme-linked immunosorbent assay. LCI was calculated using the formula: total cholesterol × triglyceride × low-density lipoprotein cholesterol/high-density lipoprotein cholesterol. RBP-4 ≥4 ng/ml, LCI ≥16 and LCI ≥16 + RBP-4 ≥4 ng/ml were new independent risk factors of ACS, and OR value of LCI ≥16 + RBP-4 ≥4 ng/ml was higher than that of RBP-4 and LCI combined (all p < 0.05). The AUC for LCI + RBP-4 was higher than that for LCI and RBP-4 individually. The risk of high LCI in 1 lesion vessel was greater than those of 2 or ≥3 lesion vessels (all p < 0.05). In 1 lesion vessel or ≥3 lesion vessels group, the risk associated with LCI and RBP-4 combined was higher than the risk of LCI or RBP-4 alone (all p < 0.05). The risk of hypertension, diabetes mellitus, smoking and history of MI increased with numbers of vessels lesion (all p < 0.05). Increase in RBP-4 and LCI values were found to be independent risk factors for ACS, and the risk of the combined rise in LCI and RBP-4 values was higher than LCI or RBP-4 alone. The combined tests of LCI and RBP-4 might be a potential diagnostic marker for ACS.

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“…Netrin-1 inactivated macrophage migration and supported chemoattraction of coronary artery smooth muscles. Netrin-1 also strongly reduces leukocyte recruitment into the vascular wall in atherosclerosis, and lack or inhibition of Netrin-1 by proatherogenic factors has shown to increase leukocyte adhesion to the endothelium [ 34 , 74 , 75 ].…”

Section: Netrin and Diabetic Complicationsmentioning

confidence: 99%

Netrin as a Novel Biomarker and Its Therapeutic Implications in Diabetes Mellitus and Diabetes-Associated Complications

Yimer

Zewdie

Hishe

2018

Journal of Diabetes Research

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Diabetes is a multifactorial metabolic syndrome and is one of the shared long-lasting illnesses globally. It is linked to long-term microvascular and macrovascular complications that contribute to disability, compromised quality of life, and reduction in lifespan, which eventually leads to death. This disease is not only incurring significant economic burden but also adversely affects the patients, caregivers, communities, and the society at large. The interruption of diabetes progress and its complications is a primary focus of scientific communities. In spite of various diagnostic modalities for diabetes, there is a limited marker to investigate the risk and progress of its complications. Netrin has recently received more attention as a biomarker of diabetes and a broader range of long-term complication. Therefore, the impetus of this review is to exhaustively discuss the role of Netrin as a potential biomarker and its therapeutic implication in diabetes and diverse sets of microvascular and macrovascular complications of diabetes. It also discourses the possible mechanisms of Netrin for the said pharmacological effect for a better understanding of the development and progression of diabetes and its complications in relation to this protein. It enables protective measures to be applied at the subclinical stage and the responses to preventive or therapeutic measures to be scrutinized. Besides, it might also facilitate the appraisal of novel therapeutic options for diabetes and various complications through modifying the endogenous Netrin and provide surrogate endpoints for intervention.

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Netrin-1 is associated with macrophage infiltration and polarization in human epicardial adipose tissue in coronary artery disease

Abstract: Findings suggest a link between enhanced netrin-1 expression in EAT and macrophage infiltration and polarization in patients with CAD.

Cited by 22 publications

References 28 publications

Overexpression of scavenger receptor and infiltration of macrophage in epicardial adipose tissue of patients with ischemic heart disease and diabetes

Overexpression of scavenger receptor and infiltration of macrophage in epicardial adipose tissue of patients with ischemic heart disease and diabetes

The correlation of retinol-binding protein-4 and lipoprotein combine index with the prevalence and diagnosis of acute coronary syndrome

Netrin as a Novel Biomarker and Its Therapeutic Implications in Diabetes Mellitus and Diabetes-Associated Complications

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