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The immunology of atherosclerosis
Anton Gisterå1, Göran K Hansson1
1Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, SE-17176 Stockholm, Sweden.
Insights
Cardiovascular disease and atherosclerosis, a chronic inflammatory condition, are leading global causes of death. Chronic kidney disease accelerates atherosclerosis, increasing cardiovascular event risk, highlighting the need for novel therapies.
Area of Science:
- Cardiovascular medicine
- Nephrology
- Immunology
Background:
- Cardiovascular disease (CVD) is the primary cause of mortality globally, affecting both the general population and individuals with chronic kidney disease (CKD).
- Atherosclerosis, a chronic inflammatory process, underlies most cardiovascular events and is accelerated by CKD through enhanced inflammation and altered lipid metabolism.
- The development of atherosclerotic plaques involves lipoprotein retention, recruitment of macrophages and T helper type 1 (TH1) cells, and immune responses to modified lipoproteins.
Purpose of the Study:
- To elucidate the mechanisms by which chronic kidney disease (CKD) accelerates atherosclerosis.
- To explore the roles of various immune cells, including T helper type 1 (TH1), regulatory T cells, and TH17 cells, in the pathogenesis of atherosclerotic plaques.
- To identify potential therapeutic targets for stabilizing atherosclerotic plaques and managing arterial inflammation, particularly in patients with CKD.
Main Methods:
- Review of existing literature on cardiovascular disease, chronic kidney disease, and atherosclerosis.
- Analysis of the immunological pathways involved in plaque formation and progression.
- Examination of the impact of T cell subsets on atherosclerotic lesion development and stability.
Main Results:
- CKD exacerbates atherosclerosis by increasing inflammation and disrupting lipid metabolism.
- TH1 cells play a critical role in initiating and perpetuating inflammation in atherosclerotic plaques by responding to modified LDL apolipoprotein B100.
- Regulatory T cells can suppress inflammation, while TH17 cells may promote plaque fibrosis, indicating complex immune involvement.
Conclusions:
- Atherosclerosis is a complex inflammatory disease accelerated by CKD, necessitating novel therapeutic strategies.
- Targeting arterial inflammation and plaque stabilization holds promise for reducing cardiovascular mortality, with potential benefits for CKD patients.
- Further research into the specific roles of different T cell subsets could lead to more effective treatments for atherosclerosis.
Abstract:
Cardiovascular disease is the leading cause of death worldwide, both in the general population and among patients with chronic kidney disease (CKD). In most cases, the underlying cause of the cardiovascular event is atherosclerosis - a chronic inflammatory disease. CKD accelerates atherosclerosis via augmentation of inflammation, perturbation of lipid metabolism, and other mechanisms. In the artery wall, subendothelial retention of plasma lipoproteins triggers monocyte-derived macrophages and T helper type 1 (TH1) cells to form atherosclerotic plaques. Inflammation is initiated by innate immune reactions to modified lipoproteins and is perpetuated by TH1 cells that react to autoantigens from the apolipoprotein B100 protein of LDL. Other T cells are also active in atherosclerotic lesions; regulatory T cells inhibit pathological inflammation, whereas TH17 cells can promote plaque fibrosis. The slow build-up of atherosclerotic plaques is asymptomatic, but plaque rupture or endothelial erosion can induce thrombus formation, leading to myocardial infarction or ischaemic stroke. Targeting risk factors for atherosclerosis has reduced mortality, but a need exists for novel therapies to stabilize plaques and to treat arterial inflammation. Patients with CKD would likely benefit from such preventive measures.