Molecular Mechanisms in Atherosclerosis and Vascular Inflammation

Atherosclerosis is a chronic inflammatory disorder of the arterial wall initiated by endothelial dysfunction and exacerbated by lipid retention. Modified low-density lipoprotein (LDL), particularly its oxidised form, accumulates within the intima and triggers endothelial activation, up-regulating adhesion molecules that recruit circulating monocytes. These monocytes differentiate into macrophages and internalise oxidised LDL via scavenger receptors, becoming foam cells that secrete pro-inflammatory cytokines and matrix-remodelling enzymes. Reactive oxygen species (ROS) generated by activated immune cells and dysfunctional mitochondria further amplify local oxidative stress and inflammatory signalling. Key intracellular pathways such as nuclear factor-κB (NF-κB), NLRP3 inflammasome assembly and toll-like receptor (TLR) cascades drive cytokine production, while counter-regulatory mechanisms involving AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and the antioxidant transcription factor Nrf2 modulate cellular survival and redox balance. Vascular smooth muscle cells contribute to plaque stability or vulnerability by migrating into the intima, proliferating and synthesising extracellular matrix components under the influence of transforming growth factor-β and mitogen-activated protein kinases. Emerging evidence highlights the role of non-coding RNAs, exosome-mediated communication and targeted nanodelivery systems in reshaping inflammatory networks and lipid handling. Understanding these interconnected molecular processes is critical for developing therapies to stabilise plaques, promote regression and reduce the global burden of cardiovascular disease.

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Molecular Mechanisms in Atherosclerosis and Vascular Inflammation publication trend

The graph below shows the total number of articles in molecular mechanisms in atherosclerosis and vascular inflammation across all publications each year (not limited to Nature Index journals).

Technical terms

Endothelial dysfunction: Impairment of the inner vascular lining leading to reduced nitric oxide bioavailability and increased expression of adhesion molecules.

Oxidised low-density lipoprotein (ox-LDL): LDL modified by oxidative reactions that promotes uptake by macrophages and inflammatory signalling.

Foam cell: Lipid-laden macrophage within atherosclerotic plaques, formed by excessive uptake of modified lipoproteins.

Reactive oxygen species (ROS): Highly reactive oxygen derivatives that contribute to oxidative stress and activation of inflammatory pathways.

Inflammasome: A multiprotein complex that senses danger signals to activate caspase-1 and release pro-inflammatory cytokines such as interleukin-1β.

References

1. Synergistic dual cell therapy for atherosclerosis regression: ROS-responsive Bio-liposomes co-loaded with Geniposide and Emodin. Journal of Nanobiotechnology (2024).
2. Fluorescent gold nanoclusters possess multiple actions against atherosclerosis. Redox Biology (2024).
3. Salvia miltiorrhiza and Tanshinone IIA reduce endothelial inflammation and atherosclerotic plaque formation through inhibiting COX-2. Biomedicine & Pharmacotherapy (2023).
4. Role of Lipid Accumulation and Inflammation in Atherosclerosis: Focus on Molecular and Cellular Mechanisms. Frontiers in Cardiovascular Medicine (2021).