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Updated: Jun 14, 2025
Quantification of Monocyte Transmigration and Foam Cell Formation from Individuals with Chronic Inflammatory Conditions
Published on: October 17, 2017
CD47-SIRPα signaling-inspired engineered monocytes for preventing the progression of atherosclerotic plaques
Qing Xia1, Feila Liu1, Yue Zhou1
1School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, 400054, China.
Abstract:
The accumulation of foam cells in the subendothelial space of the vascular wall to form plaques is the real cause of atherosclerotic lesions. Conventional interventions, such as statins and anti-cytokine or anti-inflammatory therapies, suffer problems in terms of their short therapeutic outcomes and potential disruption of the immune system. The development of more efficient therapeutics to restrict the initial progression of plaques appears to be crucial for treating and preventing atherosclerosis. Decreasing foam cell formation by reversing the excessive phagocytosis of modified low-density lipoprotein (LDL) in macrophages is highly desirable. Here, we developed a strategy based on engineered monocytes to dynamically regulate lipid uptake by macrophages inspired by a CD47-SIRPα signaling-induced defect in the phagocytosis of lesional macrophages at the advanced stage of AS. Briefly, a complex called CD47p-GQDs-miR223, which is designed to interact with SIRPα, was synthesized to remodel monocytes by decreasing the uptake of oxidized LDL through the activation of CD47-SIRPα signaling. After injection, these monocytes compete for recruitment to atherosclerotic plaques, release gene drugs and mediate anti-inflammatory phenotypic remodeling of the aboriginal macrophages, effectively inhibiting the development of foam cells. Our strategy provides a new therapeutic for preventing the progression of atherosclerosis.
Insights
Engineered monocytes target atherosclerotic plaques by reducing modified low-density lipoprotein (LDL) uptake in macrophages. This novel strategy inhibits foam cell formation, offering a new therapeutic approach for atherosclerosis prevention.
Area of Science:
- Biomedical Engineering
- Cardiovascular Research
- Immunology
Background:
- Atherosclerotic lesions result from foam cell accumulation in vascular walls.
- Current therapies like statins have limitations, including short-term efficacy and immune system disruption.
- Targeting foam cell formation by modulating macrophage lipid uptake is crucial for atherosclerosis treatment.
Purpose of the Study:
- To develop an innovative therapeutic strategy for atherosclerosis by engineering monocytes.
- To inhibit foam cell development by regulating macrophage lipid uptake.
- To leverage CD47-SIRPα signaling for therapeutic intervention in atherosclerosis.
Main Methods:
- Synthesized a CD47p-GQDs-miR223 complex to interact with SIRPα.
- Engineered monocytes to decrease oxidized low-density lipoprotein (LDL) uptake via CD47-SIRPα signaling.
- Injected modified monocytes to compete for plaque recruitment and remodel resident macrophages.
Main Results:
- Engineered monocytes effectively reduced modified LDL uptake in macrophages.
- Injected monocytes localized to atherosclerotic plaques and mediated anti-inflammatory effects.
- The strategy demonstrated inhibition of foam cell formation and atherosclerosis progression.
Conclusions:
- Engineered monocytes offer a promising new therapeutic avenue for atherosclerosis.
- Modulating CD47-SIRPα signaling presents a viable strategy to control foam cell accumulation.
- This approach provides a novel method for preventing the progression of atherosclerotic lesions.
