Nestin(+) cells direct inflammatory cell migration in atherosclerosis

Area of Science:

• Cardiovascular Biology
• Immunology
• Stem Cell Biology

Background:

• Atherosclerosis is a major cause of death, involving endothelial and smooth muscle cells.
• The role of other mesenchymal cells, specifically nestin-expressing cells, in atherogenesis is not fully understood.
• Bone marrow (BM) nestin(+) cells are known to influence monocyte egress during infections.

Purpose of the Study:

• To investigate the role of nestin(+) cells in regulating inflammatory cell migration during chronic inflammation, particularly atherosclerosis.
• To determine if nestin(+) cells contribute to atheroma plaque formation and progression.

Main Methods:

• Utilized Apolipoprotein E (ApoE) knockout mice on a high-fat diet.
• Examined the regulation of inflammatory monocyte and neutrophil egress by BM nestin(+) cells.
• Assessed the contribution of nestin(+) stromal cells to aortic atheroma plaques.
• Investigated the effect of Mcp1 deletion in nestin(+) cells versus endothelial cells on inflammatory cell infiltration and atherosclerosis.

Main Results:

• BM nestin(+) cells were found to regulate the egress of inflammatory monocytes and neutrophils in ApoE knockout mice.
• Nestin(+) stromal cells significantly increased in the aorta and contributed to atheroma plaque formation.
• Mcp1 deletion specifically in nestin(+) cells, but not endothelial cells, led to increased circulating inflammatory cells but decreased aortic infiltration, delaying plaque formation and calcification.

Conclusions:

• Nestin-expressing cells play a crucial role in directing inflammatory cell migration during atherosclerosis.
• Nestin(+) cells are significant contributors to atheroma plaque development.
• Targeting nestin(+) cells represents a potential therapeutic avenue for atherosclerosis and related vascular complications.