CD14++CD16+ monocytes and cardiovascular outcome in patients with chronic kidney disease

Rogačev, Kyrill S.; Seiler, Sarah; Zawada, Adam M.; Reichart, B; Herath, Esther; Röth, Daniel; Ulrich, Christof; Fliser, Danilo; Heine, Gunnar H.

doi:10.1093/eurheartj/ehq371

Cited by 278 publications

(289 citation statements)

References 38 publications

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“…Evidence indicates that intermediate monocytes are important in the pathology of cardiovascular diseases. 19,20) The subsets show high activation and inflammatory potential by selective upregulating of genes (AIF1 and TGFB1) linked to the inflammatory processes and display the ability to produce reactive oxygen species. 21,22) Therefore, the biological behaviour of these monocytes in AMI patients with diabetes should be determined because these patients are associated with increased immediate and long-term systemic inflammation, [23][24][25] especially in small and large blood vessels.…”

Section: Discussionmentioning

confidence: 99%

“…However, our results did not support the validity of these findings in all coronary artery diseases because we only examined the number of the cells in a certain population of STEMI patients with diabetes. Recent studies 19,28) have mainly focused on the prominence of CD16 + monocytes but not CD16 -monocytes in inflammatory diseases, such as AMI and diabetes. The accumulation of such cells in peripheral blood mainly functioned in inducing and perpetuating the inflammatory process in patients with acute and chronic inflammatory diseases.…”

Section: Discussionmentioning

confidence: 99%

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Intermediate Monocytes Lead to Enhanced Myocardial Remodelling in STEMI Patients With Diabetes

Zhang

2015

Int. Heart J.

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SummaryThis study aimed to evaluate the potential associations of intermediate monocytes (CD14 ++ CD16 + ) with myocardial remodelling in ST segment elevation myocardial infarction (STEMI) patients with diabetes.A total of 67 STEMI patients with diabetes were enrolled. The control group consisted of 65 STEMI patients without diabetes. All patients received emergency medical services for reperfusion therapy in less than 12 hours after onset of AMI. Blinded to patient clinical characteristics, monocyte subset analysis was performed using flow cytometry immediately after admission. mRNA of Chemokine Decoy Receptor D6 in each subset of monocytes was validated by Q-PCR. Expression of CCL2 in patient plasma was determined with an Elisa kit. Infarct size and left ventricular ejection fraction (LVEF) were measured using 3-dimensional echocardiography 3 days and 6 months after AMI. The incidences of recurrent cardiovascular events and death in each group were measured using the Kaplan-Meier estimator in follow-up during the next 24 months. Cox proportional-hazard models were further used to analyze the relationship of monocyte cell counts and event-free survival after adjusting for confounding factors.The number of circulating intermediate monocytes was significantly correlated with LVEF% and infarct size (r = -0.32; P = 0.008; r = 0.57, P < 0.001) in STEMI patients with diabetes compared with those without diabetes 6 months after AMI. Chemokine Decoy Receptor D6 transcript levels were lower in intermediate monocytes of STEMI patients with diabetes compared to the subsets in STEMI patients without diabetes (P < 0.001). Higher levels of CCL2 (pg/mL) were observed in STEMI patients with diabetes compared to STEMI patients without diabetes (P < 0.001). During a mean follow-up period of 24 ± 1 month, recurrent cardiovascular events or death occurred in 23 patients belonging to the STEMI with diabetes group and 10 belonging to the control group. Univariate Kaplan-Meier analysis revealed that counts of the intermediate monocytes according to median showed statistical significance in STEMI patients with diabetes (P = 0.010). After full adjustment for confounding factors, the cells were found to remain independently related to recurrent cardiovascular events or death in this group (P = 0.004, 95% CI: 1.62-12.49).Intermediate monocytes were associated with LV remodelling in STEMI patients with diabetes. The cells were predictive for recurrent cardiovascular events or death in these patients. A low level of D6 mRNA in the intermediate monocytes of STEMI patients with diabetes and high level of CCL2 in these patients may partially explain the causality. (Int Heart J 2015; 56: 22-28)

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Intermediate Monocytes Lead to Enhanced Myocardial Remodelling in STEMI Patients With Diabetes

Zhang

2015

Int. Heart J.

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“…Details of the study protocol and patient characteristics were previously described in detail. 29 Briefly, the study included stable ambulatory patients with CKD Kidney Disease Improving Global Outcomes GFR stages 1-5 (n=151) as well as stable patients with ESRD on dialysis (n=95).…”

Section: Participantsmentioning

confidence: 99%

HDL Cholesterol Is Not Associated with Lower Mortality in Patients with Kidney Dysfunction

Zewinger¹,

Speer²,

Kleber

et al. 2014

Journal of the American Society of Nephrology

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In the general population, HDL cholesterol (HDL-C) is associated with reduced cardiovascular events. However, recent experimental data suggest that the vascular effects of HDL can be heterogeneous. We examined the association of HDL-C with all-cause and cardiovascular mortality in the Ludwigshafen Risk and Cardiovascular Health study comprising 3307 patients undergoing coronary angiography. Patients were followed for a median of 9.9 years. Estimated GFR (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration eGFR creatinine-cystatin C (eGFR creat-cys ) equation. The effect of increasing HDL-C serum levels was assessed using Cox proportional hazard models. In participants with normal kidney function (eGFR.90 ml/min per 1.73 m 2 ), higher HDL-C was associated with reduced risk of [P=0.60]). Moreover, Cox regression analyses revealed interaction between HDL-C and eGFR in predicting all-cause and cardiovascular mortality (P=0.04 and P=0.02, respectively). We confirmed a lack of association between higher HDL-C and lower mortality in an independent cohort of patients with definite CKD (P=0.63). In summary, higher HDL-C levels did not associate with reduced mortality risk and coronary artery disease severity in patients with reduced kidney function. Indeed, abnormal HDL function might confound the outcome of HDL-targeted therapies in these patients.

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“…Thus, these resemble the mouse M2-like monocytes in mice on chemokine receptor expression level while functionally behaves as classically proinflammatory M1-like monocytes. CD14 high CD16 int monocytes are positively strongly associated with cardiovascular events in chronic kidney subjects and with obesity in diabetic subjects [75,76].…”

Section: Human M1/m2 Cd14 High/low Cd16 Int/high Monocytesmentioning

confidence: 99%

“…The CD14 low CD16 high monocytes are considered to be the patrolling monocyte population classically observed to perform endothelium crawling in a LFA-1 dependent manner [77]. CD14 low CD16 high monocytes has been positively correlated to BMI and atherogenic lipoproteins while negatively correlated with high-density lipoprotein cholesterol implicating a role in atherogenesis as well as with obesity in diabetic subjects [75,76].…”

Section: Human M1/m2 Cd14 High/low Cd16 Int/high Monocytesmentioning

confidence: 99%

Polarization of Macrophages in Metabolic Diseases

Rosendah¹

2015

J Clin Cell Immunol

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Monocytes originate from progenitor cells in the bone marrow and traffic via the bloodstream to peripheral tissues. During both homeostasis and in responses to clear pathogens, circulating monocytes leave the bloodstream and migrate into tissues where they, following exposure to local growth factors, pro-inflammatory cytokines and microbial products, differentiate into macrophage or dendritic cell sub-populations. Type 1 diabetes (T1D) is a disease characterised by the elimination of the insulin producing β-cells in the pancreatic tissue through activation mainly of the adaptive immune system. In metabolic diseases, i.e. obesity, Type 2 diabetes (T2D) and diabetic complications, inflammation is mostly driven by macrophages and has been shown pivotal for disease progression even when blood glucose levels are well controlled. This review describes some current ideas and trends regarding the monocyte and macrophage involvement and their polarization in metabolic diseases that might open up novel therapeutic areas for the growing diabetic population.

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CD14++CD16+ monocytes and cardiovascular outcome in patients with chronic kidney disease

Abstract: We found that CD14(++)CD16(+) monocytes were independently associated with CV events in non-dialysis CKD patients. Our results support the notion that CD16(+) monocytes rather than CD16(-) monocytes are involved in human atherosclerosis.

Cited by 278 publications

References 38 publications

Intermediate Monocytes Lead to Enhanced Myocardial Remodelling in STEMI Patients With Diabetes

Intermediate Monocytes Lead to Enhanced Myocardial Remodelling in STEMI Patients With Diabetes

HDL Cholesterol Is Not Associated with Lower Mortality in Patients with Kidney Dysfunction

Polarization of Macrophages in Metabolic Diseases

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