Atherosclerosis is a chronic inflammatory disease in which macrophages play a key role. Macrophages contribute to both plaque formation and resolution. Exploring the enigmatic mechanisms of macrophages in atherosclerosis could provide new insights into their treatment.

Creative Biolabs delves into the fascinating relationship between macrophages and atherosclerosis, shedding light on their pivotal roles, their phenotypic diversity, and potential therapeutic interventions.

Macrophages in Atherosclerosis Development

Macrophages play a crucial role in the progression of atherosclerosis. Upon sensing damage or danger signals, circulating monocytes migrate to the arterial wall and differentiate into macrophages, initiating the first steps in plaque formation. They accumulate within the plaque and release inflammatory cytokines that promote inflammation and attract more immune cells to the site. Macrophages also contribute to plaque instability, increasing the risk of rupture. When a plaque ruptures, it triggers the formation of a blood clot that can completely block an artery and lead to a heart attack or stroke.

Atherosclerotic Macrophages

Macrophages are the main immune cell type in atherosclerotic plaques and play a central role in the progression of atherosclerotic inflammation. The sources of macrophages at the plaque are divided into three main categories: monocytes in the circulating blood, vascular SMCs transdifferentiated and artery-resident macrophages.

Fig. 1 Origin of macrophages in plaques. (Fang F, et al., 2023)

These cells exhibit remarkable plasticity and adaptability, assuming diverse roles ranging from lipid handling and inflammation modulation to tissue repair and immune regulation. The balance between M1 and M2 macrophages within the lesion influences plaque stability and vulnerability to rupture. M1 macrophages drive inflammation, lipid accumulation, and matrix degradation, while M2 macrophages promote tissue repair, lipid efflux, and resolution of inflammation. The interplay between these phenotypes underscores the complexity of atherosclerosis.

Regulation of Macrophages for Atherosclerosis Treatment

The intricate interplay between macrophages and atherosclerosis opens up avenues for therapeutic interventions aimed at targeting macrophage function. Creative Biolabs is spearheading efforts to decipher the intricate signaling pathways and molecular mechanisms that regulate macrophage phenotypes, paving the way for targeted interventions.

• Targeted drug delivery systems. By harnessing the unique properties of nanoparticles, therapeutic agents can be specifically delivered to macrophages within atherosclerotic plaques. This precise targeting reduces off-target effects and enhances therapeutic efficacy, allowing for more effective regulation of macrophage function.
• Immunotherapies. Researchers are actively exploring immunomodulatory strategies to skew macrophage polarization towards an anti-inflammatory M2 phenotype. By stimulating the immune system's natural defense mechanisms, immunotherapies have the potential to promote plaque stabilization, reduce inflammation, and enhance tissue repair.
• Gene editing tools. Researchers are harnessing the power of gene editing tools, such as CRISPR-Cas9, to precisely modulate gene expression in macrophages. By targeting key genes involved in macrophage polarization, researchers aim to promote atheroprotective M2 macrophage phenotypes and suppress detrimental M1 phenotypes.

Macrophages stand as central players in the complex landscape of atherosclerosis, driving disease initiation, progression, and outcomes. The phenotypic plasticity of macrophages, transitioning between pro-inflammatory and anti-inflammatory states, underscores their immense therapeutic potential. Through the development of targeted drug delivery systems, immunotherapies, gene editing tools, miRNA-based therapies, and combination approaches, researchers aim to modulate macrophage phenotypes for atheroprotective outcomes.

Creative Biolabs' unwavering commitment to exploring the intricacies of macrophage biology paves the way for innovative therapeutic strategies, offering new hope in the battle against atherosclerosis. For more information about macrophage and atherosclerosis, please feel free to contact us.

Reference

1. Fang F, et al. Tuning macrophages for atherosclerosis treatment. Regenerative Biomaterials, 2023, 10.