Morphing the Topography of Atherosclerosis

Abstract

Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) is a complex adhesion and signaling molecule expressed by endothelial cells, platelets, and leukocytes.1,2 On endothelial cells this transmembrane glycoprotein member of the immunoglobulin gene superfamily is concentrated at intercellular junctions and cycles through vesicle-like structures contiguous with the lateral plasma membrane, termed the lateral border recycling compartment.3 Homophilic adhesive interactions between PECAM-1 on leukocytes and endothelial cells mediate leukocyte migration through endothelial cell monolayers (diapedesis) in vitro and in vivo and through the perivascular basement membrane.2,4 As a signaling molecule, PECAM-1 transduces signals required for proinflammatory adhesion molecule expression by endothelial cells. However, PECAM-1 can also inhibit inflammatory and immune responses.2 Thus, PECAM-1 has the potential to influence atherogenesis in more than one way. See accompanying articles on pages 1996 and 2003 Usually the deficiency of a molecule leads to an overall increase, decrease, or no change in murine atherosclerotic lesion burden, but the distribution of lesions in the arterial tree remains unchanged, with the majority of lesions occurring in the aortic root, the lesser (inner) curvature of the ascending aorta and near ostia of arterial branches in the descending aorta.5 In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology , two articles detail independent obserations that deficiency of PECAM-1 results in an altered distribution of atherosclerotic lesions. Goel et al6 evaluated atherosclerotic lesion development in LDL receptor deficient ( ldlr −/−) mice by measuring lipid accumulation using oil red O staining in en face preparations of the aorta and cross-sections of the aortic root, as well as micro computed tomography of osmium tetroxide stained proximal aorta and …