CD31: beyond a marker for endothelial cells.

This editorial refers to ‘A CD31-derived peptide prevents angiotensin II-induced atherosclerosis progression and aneurysm formation’ by G. Fornasa et al. , pp. 30–37, this issue. CD31 is a 130 kDa platelet–endothelial cell (EC) adhesion molecule that was initially identified from ECs and platelets1 and later from blood leucocytes.2 Mature CD31 contains a short [22-amino acid (aa)] NH2-terminal peptide followed by six C2-type immunoglobulin (Ig) domains, each flanked by two conserved cysteine residues outside the cells,3 a 19 aa transmembrane domain, and a 118 aa cytoplasmic tail containing two immunotyrosine-based inhibitory motifs (ITIM)4 ( Figure 1 ) that mediate intracellular signalling. Although CD31 was initially classified as a cell adhesion molecule,3 later studies suggested that CD31 triggers downstream inhibitory signalling4 upon transhomophilic CD31 engagement during cell–cell interaction.5 CD31 signalling participates in the regulation of leucocyte detachment, T-cell activation, platelet activation, and angiogenesis, all of which are critical to the pathogenesis of atherosclerosis and abdominal aortic aneurysms (AAAs). Figure 1 CD31 protein domains and their corresponding cellular functions. Ig, immunoglobulin; aa, amino acid; ITIM, immunotyrosine-based inhibitory motif; SHP2, Src homology-2 phosphatase; Y, tyrosine. Fornasa et al. 6 use atherosclerosis-prone apolipoprotein E-deficient ( Apoe−/− ) mice to demonstrate that aa551–574—a synthetic peptide located to the carboxyl-terminal of the Ig domain 6 ( Figure 1 )—suppressed angiotensin II (Ang-II) perfusion-induced AAAs and atherosclerosis. This peptide reduced atherosclerotic lesion and peri-aortic leucocyte infiltration and increased collagen deposition in aortic root atherosclerotic plaques and the abdominal aorta. Although we typically use CD31 as …