Atherothrombosis Mechanisms in Cardiovascular Disease

Atherothrombosis represents the intersection of atherosclerotic plaque formation and thrombus development upon plaque disruption or endothelial dysfunction. Initiated by lipid accumulation within the arterial intima, the process advances through chronic inflammation, recruitment of macrophages and leukocytes, and proliferation of vascular smooth muscle cells. Endothelial injury exposes subendothelial matrix and tissue factor, triggering the coagulation cascade and platelet adhesion. Proteolytic enzymes such as thrombin and coagulation factor Xa further drive inflammatory signalling through protease-activated receptors, exacerbating plaque vulnerability. Matrix metalloproteinases degrade the fibrous cap, increasing the likelihood of rupture, whilst interactions between platelets, immune cells and endothelial cells solidify thrombus formation. Atherothrombosis underpins acute coronary syndromes and is influenced by genetic predispositions, systemic inflammatory status and haemostatic balance, making it a global health concern and a focus for targeted therapeutic strategies.

Research from Nature Portfolio

Recent studies have demonstrated that pharmacological inhibition of coagulation factor Xa with therapeutic anticoagulants can induce regression of established atherosclerotic plaques and enhance plaque stability. Animal models treated with a factor Xa inhibitor exhibited reduced macrophage infiltration, increased collagen deposition and diminished necrotic core size, indicating a shift towards a more stable lesion phenotype. In addition, experimental modulation of blood thrombogenicity via elevated prothrombin levels in murine models has been shown to precipitate plaque destabilisation and acute thrombotic events reminiscent of human coronary artery disease. This model highlights the critical role of blood–plaque interactions in precipitating atherothrombosis and underscores the potential of antithrombotic regimens to mitigate acute events.

Atherothrombosis Mechanisms in Cardiovascular Disease publication trend

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

Technical terms

Atherothrombosis: The pathological process combining atherosclerotic plaque development and thrombus formation upon plaque disruption.

Fibrous cap: A collagenous layer overlaying the lipid core of an atherosclerotic plaque that determines plaque stability.

Protease-activated receptors (PARs): Cell surface receptors activated by proteolytic cleavage, mediating responses to thrombin and coagulation factors.

Coagulation cascade: A series of enzymatic reactions culminating in the generation of thrombin and fibrin clot formation.

Matrix metalloproteinases (MMPs): A family of enzymes that degrade extracellular matrix components and modulate plaque vulnerability.

Vascular smooth muscle cells (VSMCs): Muscle cells in the arterial wall that proliferate and contribute to plaque growth and stability.

References

1. Research into New Molecular Mechanisms in Thrombotic Diseases Paves the Way for Innovative Therapeutic Approaches. International Journal of Molecular Sciences (2024).
2. The Complementary Effects of Dabigatran Etexilate and Exercise Training on the Development and Stability of the Atherosclerotic Lesions in Diabetic ApoE Knockout Mice. Pharmaceuticals (2023).
3. Targeting Coagulation Factor Xa Promotes Regression of Advanced Atherosclerosis in Apolipoprotein-E Deficient Mice. Scientific Reports (2019).
4. Targeting blood thrombogenicity precipitates atherothrombotic events in a mouse model of plaque destabilization. Scientific Reports (2015).