Immunological Mechanisms in Atherosclerosis and Cardiovascular Pathology

Atherosclerosis arises from the insidious accumulation of lipids and modified lipoproteins within the arterial intima, triggering a chronic inflammatory cascade. Endothelial dysfunction permits low-density lipoprotein oxidation and retention, generating danger-associated molecular patterns that activate innate immune cells such as monocytes, macrophages and dendritic cells. These cells infiltrate the vessel wall, differentiate into foam cells and secrete pro-inflammatory cytokines, chemokines and matrix-remodelling enzymes, shaping the nascent plaque.

Adaptive immunity further refines lesion development through distinct T and B lymphocyte subsets. Pro-atherogenic T helper 1 and T helper 17 cells release interferon-γ and interleukins that exacerbate inflammation, whereas regulatory T cells temper immune activation and promote plaque stability. B cells contribute dual roles: B-1 cells produce natural immunoglobulin M antibodies that recognise oxidation-specific epitopes and may confer protection, while B-2 cells can drive pathogenic class-switched antibody responses.

Cross-talk between innate and adaptive arms influences plaque maturation and the likelihood of rupture. Cytokine networks centred on interleukin-18, tumour necrosis factor and interleukin-1β amplify local inflammation and impact collagen synthesis and fibrous cap integrity. In the setting of myocardial infarction, immune cells coordinate both injury and repair, underscoring the continuum between atherogenesis and post-ischaemic remodelling.

Understanding these immunological pathways has global significance, as cardiovascular disease remains a leading cause of mortality. Insights into immune cell programming and antigen-specific responses are guiding the development of immunomodulatory therapies, vaccines and precision-medicine approaches aimed at reducing plaque burden and preventing acute events.

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Immunological Mechanisms in Atherosclerosis and Cardiovascular Pathology publication trend

The graph below shows the total number of articles in immunological mechanisms in atherosclerosis and cardiovascular pathology across all publications each year (not limited to Nature Index journals).

Technical terms

Innate immunity: The first line of defence relying on non-specific cells and receptors to detect and clear pathogens or modified self.

Adaptive immunity: The antigen-specific arm of the immune system involving T and B lymphocytes that develop memory and tailored responses.

Foam cell: A lipid-laden macrophage that accumulates oxidised lipoproteins and contributes to plaque growth.

T follicular helper (Tfh) cell: A specialised CD4+ T cell subset that supports B-cell maturation and antibody class switching.

Regulatory T (Treg) cell: A CD4+ T cell subset that suppresses immune responses and maintains tolerance.

Marginal zone B (MZB) cell: A spleen-resident B cell subset that rapidly produces natural immunoglobulin M in response to blood-borne antigens.

References

1. Marginal zone B cells produce ‘natural’ atheroprotective IgM antibodies in a T cell–dependent manner. Cardiovascular Research (2024).
2. Hematopoietic PI3Kδ deficiency aggravates murine atherosclerosis through impairment of regulatory T cells. JCI Insight (2024).
3. Single-cell profiling of CD11c+ B cells in atherosclerosis. Frontiers in Immunology (2024).
4. Targeting the adaptive immune continuum in atherosclerosis and post-MI injury. Atherosclerosis (2024).