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NKT cells in cardiovascular diseases
Gijs H M van Puijvelde1, Johan Kuiper1
1Division of Biopharmaceutics, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333CC Leiden, The Netherlands.
Insights
Natural killer T (NKT) cells contribute to atherosclerosis development by releasing harmful substances. Targeting these pro-atherogenic NKT cells offers a promising new strategy for cardiovascular disease prevention and treatment.
Area of Science:
- Immunology
- Cardiovascular Medicine
- Atherosclerosis Research
Background:
- Cardiovascular diseases remain a leading global cause of death despite current treatments.
- Atherosclerosis, characterized by arterial inflammation and lipid accumulation, underlies most cardiovascular diseases.
- Natural killer T (NKT) cells and antigen-presenting cells are present in atherosclerotic lesions.
Purpose of the Study:
- To review the critical role of NKT cells in cardiovascular disease pathogenesis.
- To discuss NKT cells as potential therapeutic targets for atherosclerosis.
- To explore lipid transfer proteins and NKT cell activation mechanisms in atherosclerosis.
Main Methods:
- Literature review of studies on NKT cells in atherosclerosis.
- Analysis of NKT cell cytokine and cytotoxin secretion.
- Discussion of lipid metabolism and CD1d antigen presentation.
Main Results:
- NKT cells secrete pro-atherogenic cytokines and cytotoxins, contributing to disease progression.
- NKT cells play a significant role in the pathogenesis of atherosclerosis.
- Lipid transfer proteins are involved in CD1d loading and NKT cell activation.
Conclusions:
- Pro-atherogenic NKT cells are key players in cardiovascular disease development.
- Targeting NKT cells presents a novel therapeutic avenue for atherosclerosis.
- Understanding lipid-protein interactions is crucial for NKT cell-mediated atherosclerosis therapies.
Abstract:
Despite life-style advice and the prescription of cholesterol-lowering and anti-thrombotic drugs, cardiovascular diseases are still the leading cause of death worldwide. Therefore, there is an urgent need for new therapeutic strategies focussing on atherosclerosis, the major underlying pathology of cardiovascular diseases characterized by an accumulation of lipids in an inflamed arterial/vessel wall. CD1d-restricted lipid-sensing natural killer T (NKT) cells, bridging the innate and adaptive immunity, and CD1d-expressing antigen-presenting cells are detected in atherosclerotic lesions of mice and humans. In this review we will summarize studies that point to a critical role for NKT cells in the pathogenesis of atherosclerosis and other cardiovascular diseases by the secretion of pro-atherogenic cytokines and cytotoxins. These pro-atherogenic NKT cells are potential targets for new therapeutic strategies in the prevention and treatment of cardiovascular diseases. Additionally, proteins transferring lipids during atherosclerosis, which are also important in the loading of lipids onto CD1d and possible endogenous ligands responsible for the activation of NKT cells during atherosclerosis will be discussed.