Related Experiment Video
Updated: Aug 14, 2026
Quantification of Monocyte Chemotactic Activity In Vivo and Characterization of Blood Monocyte Derived Macrophages
Published on: August 12, 2019
Stereospecific and redox-sensitive increase in monocyte adhesion to endothelial cells by homocysteine
Otilia Postea1, Florian Krotz, Anna Henger
1Medical Policlinic, Ludwig-Maximilians University Munich, Germany.
Insights
Elevated homocysteine (Hcy) promotes atherosclerosis by increasing oxidative stress and monocyte adhesion to endothelial cells. This inflammatory response initiates and advances atherosclerotic lesion development.
Area of Science:
- Cardiovascular Biology
- Vascular Inflammation
- Atherosclerosis Pathogenesis
Background:
- Elevated homocysteine (Hcy) levels are linked to atherosclerosis development.
- Oxidative stress is implicated in Hcy's detrimental vascular effects.
- Monocyte adhesion to endothelium is a key event in atherosclerosis.
Purpose of the Study:
- To investigate Hcy's impact on endothelial cell-monocyte interactions.
- To explore the role of vascular oxidant stress and redox signaling in these interactions.
Main Methods:
- Utilized human endothelial cells (EA.hy 926, HUVEC) and THP-1 monocytic cells.
- Assessed reactive oxygen species (ROS) production, NF-kappaB activation, and ICAM-1 expression.
- Investigated the effects of superoxide scavengers and NF-kappaB inhibitors.
Main Results:
- L-Hcy, not D-Hcy, increased intracellular ROS and NF-kappaB activation in endothelial cells.
- Hcy stimulated ICAM-1 transcription and expression, leading to increased monocyte adhesion.
- Superoxide scavengers and NF-kappaB inhibition blocked Hcy-induced monocyte adhesion and ICAM-1 expression.
Conclusions:
- Hyperhomocysteinemia induces a pro-inflammatory state in the vessel wall via ROS production.
- This inflammatory cascade initiated by Hcy promotes atherosclerotic lesion development.
- Redox-sensitive pathways, particularly NF-kappaB, are critical mediators of Hcy's effects.
Objective:
Previous studies have shown that elevated homocysteine (Hcy) levels promote the development of atherosclerotic lesions in atherosclerosis-prone animal models. There is evidence that oxidant stress contributes to Hcy's deleterious effects on the vasculature. The accumulation and adhesion of monocytes to the vascular endothelium is a critical event in the development of atherosclerosis. We investigated the effects of Hcy on the interaction between human endothelial cells (EC) (EC line EA.hy 926 and primary human umbilical vein EC [HUVEC]) and the monocytic cell line THP-1, and the impact of vascular oxidant stress and redox-sensitive signaling pathways on these events.
Methods And Results:
L-Hcy, but not D-Hcy, increases the production of reactive oxygen species inside EC, enhances nuclear factor(NF)-kappaB activation, and stimulates intercellular adhesion molecule-1 (ICAM-1) RNA transcription and cell surface expression. This leads to a time- and dose-dependent increase in monocyte adhesion to ECs. Pretreatment of ECs with superoxide scavengers (MnTBAP and Tiron) or with an inhibitor of NF-kappaB activation abolished Hcy-induced monocyte adhesion, ICAM-1 expression, and nuclear translocation of NF-kappaB.
Conclusions:
These findings suggest that reactive oxygen species produced under hyperhomocysteinemic conditions may induce a proinflammatory situation in the vessel wall that initiates and promotes atherosclerotic lesion development.
