When a Friend Becomes Your Enemy: Natural Killer Cells in Atherosclerosis and Atherosclerosis-Associated Risk Factors

Abstract

Atherosclerosis (ATS), the change in structure and function of arteries with associated lesion formation and altered blood flow, is the leading cause of cardiovascular disease, the number one killer worldwide. Beyond dyslipidemia, chronic inflammation, together with aberrant phenotype and function of cells of both the innate and adaptive immune system, are now recognized as relevant contributors to atherosclerosis onset and progression. While the role of macrophages and T cells in atherosclerosis has been addressed in several studies, Natural Killer cells (NKs) represent a poorly explored immune cell type, that deserves attention, due to NKs’ emerging contribution to vascular homeostasis. Furthermore, the possibility to re-polarize the immune system has emerged as a relevant tool to design new therapies, with some succesfull exmples in the field of cancer immunotherapy. Thus, a deeper knowledge of NK cell pathophysiology in the context of atherosclerosis and atherosclerosis-associated risk factors could help developing new preventive and treatment strategies, and decipher the complex scenario/history from “the risk factors for atherosclerosis” Here, we review the current knowledge about NK cell phenotype and activities in atherosclerosis and selected atherosclerosis risk factors, namely type-2 diabetes and obesity, and discuss the related NK-cell oriented environmental signals.

The Causal Relationship Between Blood Lipids and Systemic Lupus Erythematosus Risk: A Bidirectional Two-Sample Mendelian Randomization Study

“…Dyslipidemia is a risk factor for many diseases, such as cardiovascular disease (CVD), metabolic syndrome, and obesity ( Palano et al, 2021 ; Alsayed et al, 2022 ; Subramanian, 2022 ). Dyslipidemia is mainly reflected by the abnormalities in low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides (TG), and total cholesterol (TC).…”

The Influence of Polyphenols on Atherosclerosis Development

“…Atherosclerosis is an inflammatory chronic vascular disease primarily associated with oxidative stress and endothelial dysfunction that leads to manufacturing CVD [ 23 , 24 ]. Numerous studies confirm that hyperlipidaemia alone is not sufficient for atherosclerosis development; rather, inflammation becomes an additional stimulus [ 25 ].…”

Interrogating Atherosclerotic Plaque Biology Through Responses to Cardiovascular Risk Management and Imaging

“…NK cells are bone marrow derived lymphocytes not passing the thymus and thus they lack the T lymphocyte marker CD3 + (CD3 -CD56 + ). As a part of the innate immune response, they are known for the surveillance of viruses and tumour growth, but less is known about NK cell responses in atherosclerotic disease (83). Murine studies show that NK cell activation is mediated either through macrophage/dendritic cell interaction, or through the direct stimulus from IL-15, IL-12 or IL-18, causing a hyperactivated state that is considered pro-atherogenic, and it has been proposed that NK cell contribution to the atherogenic process involves cytotoxic factors and cytokine secretion (84)(85)(86)(87).…”

“…There has been contrasting evidence of NK cell function in plaque progression, with NK cells displaying in part antiinflammatory cytokines (like IL-10, IL-4, and IL-13) and on the other hand proinflammatory cytokines like IFN-γ (88). One explanation for the non-uniform reports on NK cell participation in atherosclerosis, might be that different murine models have been used in different studies (83). Another complexity is the various not yet fully characterised NK cell sub lineages that might play different and sometimes contrasting roles in atherosclerotic disease pathogenesis (79).…”