Neutrophils as a Novel Target of Modified Low-Density Lipoproteins and an Accelerator of Cardiovascular Diseases

Obama, Takashi; Itabe, Hiroyuki

doi:10.3390/ijms21218312

Cited by 19 publications

(12 citation statements)

References 139 publications

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“…35 Oxidatively modified low-density lipoprotein also plays an important role in atherosclerosis through foam cell formation, enhancing NET-mediated inflammatory responses in vascular cells through neutrophil activation. 36 Previous reports indicated that neutrophils are strongly associated with in-hospital mortality and major adverse cardiovascular and cerebrovascular events. 37 A lower lymphocyte count was associated with atherosclerosis progression and adverse clinical outcomes in patients with myocardial infarction.…”

Section: Discussionmentioning

confidence: 99%

The Prognostic Value of a Derived Neutrophil-Lymphocyte Ratio in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

Fan

Zhang

Gao

et al. 2021

Clin Appl Thromb Hemost

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The systemic immune-inflammatory index (SII) and derived neutrophil-lymphocyte ratio (dNLR) are novel indexes that simultaneously reflect the host inflammatory and immune status and have prognostic value in some cancers. SII was associated with major cardiovascular events in coronary artery disease patients who received percutaneous coronary intervention (PCI). However, dNLR correlations with clinical outcomes in acute coronary syndrome (ACS) patients undergoing PCI remain unclear. This study aimed to elucidate the predictive values of SII and dNLR on the long-term prognosis of patients with ACS undergoing PCI. In total, 1,553 ACS patients undergoing PCI were consecutively enrolled from January 2016 to December 2018. The subjects were divided into high and low SII and dNLR groups for comparison (high vs. low). The SII and dNLR cutoff values for predicting major adverse cardiovascular events (MACE) were calculated using receiver operating characteristic curves, and Kaplan-Meier curves and Cox regression models were used for survival analyses. The endpoint was a MACE, which included all-cause mortality and rehospitalization for severe heart failure during follow-up. The Kaplan-Meier curves showed that a higher SII or dNLR value was associated with a higher risk of MACE (all P < 0.001). Multivariate Cox regression models showed that SII (hazard ratio [HR]: 2.545; 95% confidence interval [CI]: 1.416-4.574; P = 0.002) and dNLR (HR: 2.610, 95% CI: 1.454-4.685, P = 0.001) were independent predictors for MACE. dNLR may be a suitable laboratory marker to identify high-risk ACS patients after PCI.

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Section: Discussionmentioning

confidence: 99%

The Prognostic Value of a Derived Neutrophil-Lymphocyte Ratio in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

Fan

Zhang

Gao

et al. 2021

Clin Appl Thromb Hemost

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“…NETs induce oxidative stress leading to oxidization of HDL particles, thereby reducing their beneficial cholesterol efflux ability ( 176 ). In addition, NETs contain myeloperoxidase, which has the potential to modulate LDL oxidation ( 177 , 178 ). In humans, inflammasome activation and NETosis may result in atherosclerotic plaque erosion and thrombosis, especially in patients with T2DM, clonal hematopoiesis or chronic kidney disease ( 179 ).…”

Section: Current Perspectives and Limitationsmentioning

confidence: 99%

Metformin, Macrophage Dysfunction and Atherosclerosis

Feng

Chen

et al. 2021

Front. Immunol.

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Metformin is one of the most widely prescribed hypoglycemic drugs and has the potential to treat many diseases. More and more evidence shows that metformin can regulate the function of macrophages in atherosclerosis, including reducing the differentiation of monocytes and inhibiting the inflammation, oxidative stress, polarization, foam cell formation and apoptosis of macrophages. The mechanisms by which metformin regulates the function of macrophages include AMPK, AMPK independent targets, NF-κB, ABCG5/8, Sirt1, FOXO1/FABP4 and HMGB1. On the basis of summarizing these studies, we further discussed the future research directions of metformin: single-cell RNA sequencing, neutrophil extracellular traps (NETs), epigenetic modification, and metformin-based combination drugs. In short, macrophages play an important role in a variety of diseases, and improving macrophage dysfunction may be an important mechanism for metformin to expand its pleiotropic pharmacological profile. In addition, the combination of metformin with other drugs that improve the function of macrophages (such as SGLT2 inhibitors, statins and IL-1β inhibitors/monoclonal antibodies) may further enhance the pleiotropic therapeutic potential of metformin in conditions such as atherosclerosis, obesity, cancer, dementia and aging.

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“…Oxidized low-density lipoprotein (oxLDL), which easily accumulates in macrophages, is used as an atherosclerosis-inducing molecule. Many studies have shown that it stimulates neutrophils to form NETs ( 33 ). The specific deletion of peptidyl arginine deiminase-4 (PAD4) reduces the formation of NETs and significantly alleviates atherosclerosis, complications, and inflammation caused by macrophages ( 34 , 35 ).…”

Section: The Role Of Nets In Atherosclerosis and Arterial Thrombosismentioning

confidence: 99%

The Emerging Role of Neutrophil Extracellular Traps in Arterial, Venous and Cancer-Associated Thrombosis

Zhou

Tao

Shen

et al. 2021

Front. Cardiovasc. Med.

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Neutrophils play a vital role in the formation of arterial, venous and cancer-related thrombosis. Recent studies have shown that in a process known as NETosis, neutrophils release proteins and enzymes complexed to DNA fibers, collectively called neutrophil extracellular traps (NETs). Although NETs were originally described as a way for the host to capture and kill bacteria, current knowledge indicates that NETs also play an important role in thrombosis. According to recent studies, the destruction of vascular microenvironmental homeostasis and excessive NET formation lead to pathological thrombosis. In vitro experiments have found that NETs provide skeletal support for platelets, red blood cells and procoagulant molecules to promote thrombosis. The protein components contained in NETs activate the endogenous coagulation pathway to promote thrombosis. Therefore, NETs play an important role in the formation of arterial thrombosis, venous thrombosis and cancer-related thrombosis. This review will systematically summarize and explain the study of NETs in thrombosis in animal models and in vivo experiments to provide new targets for thrombosis prevention and treatment.

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Neutrophils as a Novel Target of Modified Low-Density Lipoproteins and an Accelerator of Cardiovascular Diseases

Cited by 19 publications

References 139 publications

The Prognostic Value of a Derived Neutrophil-Lymphocyte Ratio in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

The Prognostic Value of a Derived Neutrophil-Lymphocyte Ratio in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

Metformin, Macrophage Dysfunction and Atherosclerosis

The Emerging Role of Neutrophil Extracellular Traps in Arterial, Venous and Cancer-Associated Thrombosis

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