Molecular Mechanisms of Coronary Artery Disease

Coronary artery disease arises from a complex interplay of lipid accumulation, inflammatory activation and vascular remodelling within the arterial wall. It initiates with endothelial dysfunction driven by disturbed shear stress and oxidative injury, which increases permeability to low-density lipoprotein (LDL) particles. Oxidation of LDL fosters recruitment of monocytes that differentiate into macrophages, take up oxidised LDL and become lipid-laden foam cells. Sustained inflammation stimulates vascular smooth muscle cells to proliferate and migrate, depositing extracellular matrix and forming a fibrous cap. Vulnerable regions often feature reduced cap integrity, neovascular networks prone to intraplaque haemorrhage and infiltrating senescent macrophages secreting pro-inflammatory cytokines. At the molecular level, dysregulated cholesterol handling, altered glutamine/glutamate flux, epigenetic reprogramming and non-coding RNA networks drive key transitions from stable to unstable plaque. These mechanisms underpin clinical complications such as plaque rupture, thrombosis and myocardial infarction, and they present targets for novel diagnostic and therapeutic strategies.

Research from Nature Portfolio

Analysis of atherosclerotic plaques across carotid, femoral and infrapopliteal beds has revealed distinct gene expression signatures that reflect regional differences in calcification and inflammation. Immune-related transcripts dominate in carotid lesions, whereas bone development and endochondral pathways are enriched in femoral plaques, offering insights into the heterogeneity of plaque stability. A complementary study of advanced peripheral atherosclerotic plaques versus healthy arteries identified hundreds of differentially expressed genes, with osteopontin and matrix metalloproteinases markedly upregulated and lipid-associated factors downregulated. Pathway analysis emphasised leukocyte trafficking and inflammatory signalling as central to disease progression across vascular territories. Together, these findings underscore the importance of spatially resolved molecular profiling in understanding how local microenvironments influence plaque evolution and risk of coronary events.

Molecular Mechanisms of Coronary Artery Disease publication trend

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

Technical terms

Endothelial dysfunction: Impairment of the inner vessel lining leading to increased permeability and pro-inflammatory signalling.

Oxidised LDL (oxLDL): LDL particles modified by oxidative processes that promote foam cell formation and inflammation.

Foam cells: Lipid-laden macrophages that accumulate within the intima and contribute to plaque growth.

Intraplaque haemorrhage (IPH): Bleeding into the plaque core from fragile neovessels, destabilising the fibrous cap.

Macrophage senescence: Age-related or stress-induced state in macrophages characterised by chronic secretion of pro-inflammatory factors.

Genome-scale metabolic network (GEM): Computational model integrating gene and metabolite data to map cellular metabolic fluxes.

References

1. Endothelial Dysfunction, Inflammation and Coronary Artery Disease: Potential Biomarkers and Promising Therapeutical Approaches. International Journal of Molecular Sciences (2021).
2. Identification of genomic differences among peripheral arterial beds in atherosclerotic and healthy arteries. Scientific Reports (2018).
3. Differentially expressed genes and canonical pathway expression in human atherosclerotic plaques – Tampere Vascular Study. Scientific Reports (2017).
4. Genome-scale metabolic network of human carotid plaque reveals the pivotal role of glutamine/glutamate metabolism in macrophage modulating plaque inflammation and vulnerability. Cardiovascular Diabetology (2024).
5. A Transcriptomic Analysis of Smoking-Induced Gene Expression Alterations in Coronary Artery Disease Patients. International Journal of Molecular Sciences (2023).
6. Unveiling the role of ABI3 and hub senescence-related genes in macrophage senescence for atherosclerotic plaque progression. Inflammation Research (2023).