Inflammatory Mechanisms in Atherosclerotic Cardiovascular Disease

Atherosclerosis arises from the interplay between lipid retention in the arterial intima and a persistent inflammatory response. Endothelial dysfunction, triggered by turbulent flow and modified lipoproteins, leads to up-regulation of adhesion molecules and chemokines that recruit monocytes and lymphocytes. Within nascent plaques, monocytes differentiate into macrophages that internalise oxidised lipids, becoming foam cells and secreting pro-inflammatory cytokines such as interleukin-1β. Activation of pattern recognition receptors and the NLRP3 inflammasome amplifies local inflammation, while adaptive immune cells, including effector T-helper subsets, further shape lesion progression. Chronic inflammation destabilises the fibrous cap through matrix metalloproteinases, increasing the risk of plaque rupture and acute thrombotic events. Conversely, specialised pro-resolving mediators and regulatory immune cells can limit inflammation and promote plaque stability. Understanding these mechanisms has informed novel therapeutic strategies, from cytokine blockade to modulation of immunometabolism, with the aim of reducing cardiovascular events worldwide.

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Inflammatory Mechanisms in Atherosclerotic Cardiovascular Disease publication trend

The graph below shows the total number of articles in inflammatory mechanisms in atherosclerotic cardiovascular disease across all publications each year (not limited to Nature Index journals).

Technical terms

Atherosclerotic plaque: A focal lesion in the arterial wall characterised by lipid deposition, inflammatory cells and fibrous tissue.

Macrophage: Innate immune cell derived from monocytes, capable of lipid uptake and cytokine production within plaques.

Cytokine: Small secreted protein that modulates inflammation and immune cell communication.

Chemokine: A subclass of cytokines that directs the migration of immune cells to sites of inflammation.

Immunometabolite: Metabolic intermediate, such as itaconate, that influences immune cell function.

Endothelial dysfunction: Impaired ability of the vascular lining to regulate tone and barrier function, promoting inflammation.

References

1. Macrophages in cardiovascular diseases: molecular mechanisms and therapeutic targets. Signal Transduction and Targeted Therapy (2024).
2. Interleukin-1 receptor accessory protein blockade limits the development of atherosclerosis and reduces plaque inflammation. Cardiovascular Research (2024).
3. Targeting the ACOD1-itaconate axis stabilizes atherosclerotic plaques. Redox Biology (2024).