Natural killer (NK) cell deficit in coronary artery disease: no aberrations in phenotype but sustained reduction of NK cells is associated with low-grade inflammation

Backteman, Karin; Ernerudh, Jan; Jonasson, Lena

doi:10.1111/cei.12210

Cited by 49 publications

(46 citation statements)

References 35 publications

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“…Another study reported decreased NK cells in patients at the time of diagnosis. Furthermore, a 12-month follow-up showed that a continued deficient in NK cells was correlated with low-grade cardiac inflammation, whereas patients that had restored circulating NK cells had little to no cardiac inflammation [65, 66]. …”

Section: Heart Disease Accompanied By Inflammationmentioning

confidence: 99%

Natural killer cells in inflammatory heart disease

Ong

Rose

Čiháková

2017

Clinical Immunology

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Despite of a multitude of excellent studies, the regulatory role of natural killer (NK) cells in the pathogenesis of inflammatory cardiac disease is greatly underappreciated. Clinical abnormalities in the numbers and functions of NK cells are observed in myocarditis and inflammatory dilated cardiomyopathy (DCMi) as well as in cardiac transplant rejection [1–6]. Because treatment of these disorders remains largely symptomatic in nature, patients have little options for targeted therapies [7, 8]. However, blockade of NK cells and their receptors can protect against inflammation and damage in animal models of cardiac injury and inflammation. In these models, NK cells suppress the maturation and trafficking of inflammatory cells, alter the local cytokine and chemokine environments, and induce apoptosis in nearby resident and hematopoietic cells [1, 9, 10]. This review will dissect each protective mechanism employed by NK cells and explore how their properties might be exploited for their therapeutic potential.

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Section: Heart Disease Accompanied By Inflammationmentioning

confidence: 99%

Natural killer cells in inflammatory heart disease

Ong

Rose

Čiháková

2017

Clinical Immunology

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“…Other studies indicate that patients with severe atherosclerosis have greater numbers of circulating NK cells (Clerc and Rouz, ); elderly patients with peripheral artery disease also have greater numbers of circulating NK cells but with reduced cytotoxic capability (Bruunsgaard et al, ). Immediately after non‐STEMI MI NK cell numbers are low and then increase over the ensuing 12 months possibly contributing to MI‐accelerated atherosclerosis; their failure to increase in some patients is associated with persistent low‐grade inflammation (Backteman et al, ). In other studies, circulating but not lymph node CD56+ NK cells are reduced in patients with acute coronary syndrome compared with patients with stable angina (Backteman et al, ).…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic lymphocytes and atherosclerosis: significance, mechanisms and therapeutic challenges

Kyaw

Peter

et al. 2017

British J Pharmacology

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Cytotoxic lymphocytes encompass natural killer lymphocytes (cells) and cytotoxic T cells that include CD8+ T cells, natural killer (NK) T cells, γ, δ (γδ)-T cells and human CD4 + CD28À T cells.These cells play critical roles in inflammatory diseases and in controlling cancers and infections. Cytotoxic lymphocytes can be activated via a number of mechanisms that may involve dendritic cells, macrophages, cytokines or surface proteins on stressed cells. Upon activation, they secrete pro-inflammatory cytokines as well as anti-inflammatory cytokines, chemokines and cytotoxins to promote inflammation and the development of atherosclerotic lesions including vulnerable lesions, which are strongly implicated in myocardial infarctions and strokes. Here, we review the mechanisms that activate and regulate cytotoxic lymphocyte activity, including activating and inhibitory receptors, cytokines, chemokine receptors-chemokine systems utilized to home to inflamed lesions and cytotoxins and cytokines through which they affect other cells within lesions. We also examine their roles in human and mouse models of atherosclerosis and the mechanisms by which they exert their pathogenic effects. Finally, we discuss strategies for therapeutically targeting these cells to prevent the development of atherosclerotic lesions and vulnerable plaques and the challenge of developing highly targeted therapies that only minimally affect the body's immune system, avoiding the complications, such as increased susceptibility to infections, which are currently associated with many immunotherapies for autoimmune diseases. LINKED ARTICLESThis article is part of a themed section on Targeting Inflammation to Reduce Cardiovascular Disease Risk. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.22/issuetoc and http://onlinelibrary.wiley.com/doi/ 10.1111/bcp.v82.4/issuetoc Abbreviation TCR, T cell receptor; MHC, major histocompablity complex; NKG2D, natural-killer group 2, member D; TRAIL, TNF-related apoptosis-inducing ligand; DNAM-1, DNAX accessory molecule-1; Clec9A, C-type lectin domain family 9 member A

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“…Expression of NK cell sensors was also decreased in MI (68). A recent study reported that chronic NK cell deficiency was associated with low-grade chronic inflammation, which indicates a protective role for NK cells in atherosclerosis and MI healing (72).…”

Section: Lymphocyte Diversity In MImentioning

confidence: 83%

Leukocyte diversity in resolving and nonresolving mechanisms of cardiac remodeling

Tourki

Halade

2017

FASEB j.

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In response to myocardial infarction (MI), time-dependent leukocyte infiltration is critical to program the acute inflammatory response. Post-MI leukocyte density, residence time in the infarcted area, and exit from the infarcted injury predict resolving or nonresolving inflammation. Overactive or unresolved inflammation is the primary determinant in heart failure pathology post-MI. Here, our review describes supporting evidence that the acute inflammatory response also guides the generation of healing and regenerative mediators after cardiac damage. Time-dependent leukocyte density and diversity and the magnitude of myocardial injury is responsible for the resolving and nonresolving pathway in myocardial healing. Post MI, the diversity of leukocytes, such as neutrophils, macrophages, and lymphocytes, has been explored that regulate the clearance of deceased cardiomyocytes by using the classic and reparative pathways. Among the innovative factors and intermediates that have been recognized as essential in acute the self-healing and clearance mechanism, we highlight specialized proresolving mediators as the emerging factor for post-MI reparative mechanisms-translational leukocyte modifiers, such as aging, the source of leukocytes, and the milieu around the leukocytes. In the clinical setting, it is possible that leukocyte diversity is more prominent as a result of risk factors, such as obesity, diabetes, and hypertension. Pharmacologic agents are critical modifiers of leukocyte diversity in healing mechanisms that may impair or stimulate the clearance mechanism. Future research is needed, with a focused approach to understand the molecular targets, cellular effectors, and receptors. A clear understanding of resolving and nonresolving inflammation in myocardial healing will help to develop novel targets with major emphasis on the resolution of inflammation in heart failure pathology.-Tourki, B., Halade, G. Leukocyte diversity in resolving and nonresolving mechanisms of cardiac remodeling.

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Natural killer (NK) cell deficit in coronary artery disease: no aberrations in phenotype but sustained reduction of NK cells is associated with low-grade inflammation

Cited by 49 publications

References 35 publications

Natural killer cells in inflammatory heart disease

Natural killer cells in inflammatory heart disease

Cytotoxic lymphocytes and atherosclerosis: significance, mechanisms and therapeutic challenges

Leukocyte diversity in resolving and nonresolving mechanisms of cardiac remodeling

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