Atherosclerosis Pathogenesis and Risk Factors

Atherosclerosis is a chronic immunoinflammatory disease of the arterial wall, predominantly affecting the intima of large and medium-sized vessels. It initiates with endothelial dysfunction, permitting retention and oxidative modification of apolipoprotein B–containing lipoproteins in the subendothelial space. Monocytes transmigrate, differentiate into macrophages and internalise lipids to become foam cells, establishing a focal inflammatory niche. Vascular smooth muscle cells migrate from the media to the intima, proliferate and secrete extracellular matrix, forming a fibrous cap over a lipid-rich necrotic core. Progression involves ongoing matrix remodelling, neovascularisation and calcification. Cap thinning or erosion can precipitate plaque rupture, exposing thrombogenic material and triggering acute ischaemic events. Traditional risk factors such as hyperlipidaemia, hypertension, smoking, diabetes and obesity synergise to accelerate lesion development and destabilisation. Ageing and genetic predisposition modulate lipid metabolism, vascular cell senescence and systemic inflammation. Emerging research points to epigenetic regulation and the gut microbiome as additional modulators of plaque initiation and stability. Insights into the interplay between lipid handling, immune activation and biomechanical forces underpin current lipid-lowering, anti-inflammatory and lifestyle interventions that substantially reduce global cardiovascular morbidity and mortality.

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Atherosclerosis Pathogenesis and Risk Factors publication trend

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Technical terms

Endothelial dysfunction: Impairment of the vascular endothelium’s ability to regulate vasomotion, barrier integrity and inflammatory responses.

Foam cell: Lipid-laden macrophage formed when monocyte-derived cells engulf modified lipoproteins in the arterial wall.

Dyslipidaemia: Abnormal plasma lipid profile, typically characterised by elevated low-density lipoprotein and/or reduced high-density lipoprotein concentrations.

Fibrous cap: Collagen-rich layer of smooth muscle cells and extracellular matrix that overlies the atheromatous core, conferring plaque stability.

Necrotic core: Central region of atherosclerotic plaque composed of cellular debris, lipids and cholesterol crystals resulting from foam cell death.

Plaque rupture: Disruption of the fibrous cap exposing the thrombogenic necrotic core to the bloodstream, precipitating acute thrombotic events.

References

1. The Aging Risk and Atherosclerosis: A Fresh Look at Arterial Homeostasis. Frontiers in Genetics (2017).
2. Atherosclerosis from Newborn to Adult—Epidemiology, Pathological Aspects, and Risk Factors. Life (2023).
3. Lipid-Induced Epigenomic Changes in Human Macrophages Identify a Coronary Artery Disease-Associated Variant that Regulates PPAP2B Expression through Altered C/EBP-Beta Binding. PLOS Genetics (2015).
4. Emerging Trends in Atherosclerosis: Time to Address Atherosclerosis From a Younger Age. Cureus (2024).
5. A multiphysics-based artificial neural networks model for atherosclerosis. Heliyon (2023).