Leukocyte influx in atherosclerosis

Area of Science:

• Cardiovascular immunology
• Inflammatory diseases
• Arterial wall biology

Background:

• Atherosclerosis is a chronic inflammatory arterial disease.
• Immune system involvement in atherosclerosis initiation, progression, and persistence is increasingly recognized.
• Various leukocytes, including T cells, B cells, NK cells, NKT cells, macrophages, dendritic cells, and mast cells, are found in atherosclerotic aortas.

Purpose of the Study:

• To review leukocyte recruitment mechanisms into the aortic wall during atherosclerosis.
• To focus on insights gained from mouse model systems.
• To highlight knowledge gaps regarding NK, NKT, and mast cell recruitment.

Main Methods:

• Review of existing literature on leukocyte recruitment in atherosclerosis.
• Focus on mechanisms involving specific adhesion molecules (e.g., selectins, ICAMs) and chemokines (e.g., CXCL1, CCL5).
• Emphasis on studies utilizing mouse models of atherosclerosis.

Main Results:

• Monocyte recruitment involves P-selectin, E-selectin, VCAM-1, ICAM-1, JAM-A, and chemokines like CXCL1, CCL5, CXCL4, CXCL7, and MIF.
• Ly6C(high) and Ly6C(low) monocyte subsets exhibit differential chemokine usage (CCL2, CX3CL1, CCL5) for aortic homing.
• T and B lymphocyte migration is L-selectin-dependent, with CCL5, CXCL10, CXCL16, CXCR6, and MIF implicated in T cell influx.

Conclusions:

• Leukocyte recruitment is a complex process critical to atherosclerosis development.
• Mouse models provide valuable insights into the mechanisms of immune cell trafficking in atherosclerosis.
• Further research is needed to elucidate the recruitment pathways of NK cells, NKT cells, and mast cells in this disease.