This study investigates the role of VCAM-1 and ICAM-1 in the initiation of atherosclerosis. VCAM-1 and ICAM-1 are endothelial adhesion molecules that promote monocyte accumulation in the arterial intima, contributing to atherogenesis. The researchers disrupted the fourth Ig domain of VCAM-1 to produce a murine Vcam1D4D allele, which reduced VCAM-1 mRNA and protein levels to 2-8% of wild-type levels. When crossed into an LDL receptor-null background and fed a cholesterol-enriched diet, Vcam1D4D/D4D mice showed a significant reduction in early atherosclerotic lesion area in the aorta compared to wild-type mice, while ICAM-1 deficiency did not alter lesion formation. This suggests that VCAM-1 plays a dominant role in the initiation of atherosclerosis, while ICAM-1 may have a more limited role. The findings indicate that VCAM-1 is crucial for the early stages of atherosclerosis, potentially by facilitating monocyte recruitment to the arterial intima.This study investigates the role of VCAM-1 and ICAM-1 in the initiation of atherosclerosis. VCAM-1 and ICAM-1 are endothelial adhesion molecules that promote monocyte accumulation in the arterial intima, contributing to atherogenesis. The researchers disrupted the fourth Ig domain of VCAM-1 to produce a murine Vcam1D4D allele, which reduced VCAM-1 mRNA and protein levels to 2-8% of wild-type levels. When crossed into an LDL receptor-null background and fed a cholesterol-enriched diet, Vcam1D4D/D4D mice showed a significant reduction in early atherosclerotic lesion area in the aorta compared to wild-type mice, while ICAM-1 deficiency did not alter lesion formation. This suggests that VCAM-1 plays a dominant role in the initiation of atherosclerosis, while ICAM-1 may have a more limited role. The findings indicate that VCAM-1 is crucial for the early stages of atherosclerosis, potentially by facilitating monocyte recruitment to the arterial intima.