Atherosclerosis Pathogenesis and Therapeutic Strategies

Atherosclerosis is a chronic vascular disorder in which lipid accumulation, inflammatory processes and cellular dysfunction converge to form plaques within arterial walls. Initiation typically follows endothelial dysfunction, permitting infiltration of apolipoprotein B-containing lipoproteins that undergo oxidative modification. Monocytes adhere to the activated endothelium, migrate into the intima and differentiate into macrophages that engulf oxidised lipids to become foam cells. Persistent inflammation driven by cytokines and proteases, combined with smooth muscle cell migration and extracellular matrix remodelling, determines plaque stability. Advanced lesions may calcify or develop a necrotic core with a thin fibrous cap, rendering plaques vulnerable to rupture, thrombosis and acute cardiovascular events. Current therapeutic strategies target major risk factors through lipid-lowering agents, antiplatelet drugs and antihypertensive therapies. Emerging approaches seek to modulate plaque inflammation, enhance macrophage resolution pathways and restore autophagy. Precision medicine, informed by molecular profiling, promises to refine risk stratification and deliver tailored interventions that address the heterogeneity of plaque phenotypes and patient populations worldwide.

Research from Nature Portfolio

Recent studies have elucidated the protective role of caspase recruitment domain-containing protein 9 (CARD9) in atherosclerosis. Genetic deletion of CARD9 in murine models was found to exacerbate lesion formation through overexpression of the scavenger receptor CD36, heightened interleukin-1β production and defective autophagy in macrophages. Pharmacological induction of autophagy with rapamycin or metformin restored lipid homeostasis, reduced macrophage death and abrogated the accelerated atherogenesis observed in CARD9-deficient animals. Transcriptomic analysis of human monocytes confirmed a comparable pro-inflammatory signature, highlighting CARD9 as a potential target for therapies aimed at bolstering macrophage resilience and limiting lipid overload.

Atherosclerosis Pathogenesis and Therapeutic Strategies publication trend

The graph below shows the total number of articles in atherosclerosis pathogenesis and therapeutic strategies across all publications each year (not limited to Nature Index journals).

Technical terms

Atherosclerotic plaque: build-up of lipids, immune cells and connective tissue within the arterial wall that may restrict blood flow and become unstable.

Foam cell: lipid-laden macrophage that has internalised oxidised lipoproteins, contributing to plaque formation.

Endothelial dysfunction: impaired function of the arterial lining, characterised by reduced vasodilation, inflammation and increased permeability.

Autophagy: cellular mechanism for degrading and recycling intracellular components, crucial for macrophage lipid handling and survival.

Cytokine: small protein secreted by immune cells that mediates inflammation and intercellular signalling.

Low-density lipoprotein (LDL): cholesterol-rich particle in the blood that can become oxidised and deposit within the arterial wall.

Macrophage polarisation: functional adaptation of macrophages towards pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes within lesions.

References

1. Proteomic Atlas of Atherosclerosis: The Contribution of Proteoglycans to Sex Differences, Plaque Phenotypes, and Outcomes. Circulation Research (2023).
2. Genetic inhibition of CARD9 accelerates the development of atherosclerosis in mice through CD36 dependent-defective autophagy. Nature Communications (2023).
3. Cytokines in atherosclerosis: Key players in all stages of disease and promising therapeutic targets. Cytokine & Growth Factor Reviews (2015).
4. Mechanistic Insights into the Oxidized Low‐Density Lipoprotein‐Induced Atherosclerosis. Oxidative Medicine and Cellular Longevity (2020).