Approximately 20% of aortic aneurysm and/or dissection (AAD) cases result from inherited disorders, including several systemic and syndromatic connective-tissue disorders, such as Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome, which are caused by mutations in the FBN1, COL3A1, and TGFBR1 and TGFBR2 genes, respectively. Nonsyndromatic AAD also has a familial background, and mutations of the ACTA2 gene were recently shown to cause familial AAD. In the present study, we conducted sequence analyses of the ACTA2 gene in 14 unrelated Japanese patients with familial thoracic AAD (TAAD), and in 26 with sporadic and young-onset TAAD. Our results identified three mutations of ACTA2, two novel [p.G152_T205del (c.616+1G>T), p.R212Q] and one reported (p.R149C), in the 14 patients with familial TAAD, and a novel mutation (p.Y145C) of ACTA2 in the 26 sporadic and young-onset TAAD patients, each of which are considered to be causative for TAAD. Some of the clinical features of these patients were the same as previously reported, whereas others were different. These findings confirm that ACTA2 mutations are important in familial TAAD, while the first sporadic and young-onset TAAD case with an ACTA2 mutation was also identified.

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Ephrin B1 and its cognate receptor, Eph receptor B2, key regulators of embryogenesis, are expressed in human atherosclerotic plaque and inhibit adult human monocyte chemotaxis. Few data exist, however, regarding the gene expression profiles of the ephrin (EFN) and Eph receptor (EPH) family of genes in atherosclerosis-related human cells. Gene expression profiles were determined of all 21 members of this gene family in atherosclerosis-related cells by reverse transcription-polymerase chain reaction analysis. The following 17 members were detected in adult human peripheral blood monocytes: EFNA1 and EFNA3 - EFNA5 (coding for ephrins A1 and A3 - A5); EPHA1, EPHA2, EPHA4 - EPHA6 and EPHA8 (coding for Eph receptors A1, A2, A4 - A6 and A8); EFNB1 and EFNB2 (coding for ephrins B1 and B2); and EPHB1 - EPHB4 and EPHB6 (coding for Eph receptors B1 - B4 and B6). THP-1 monocytic cells, Jurkat T cells and adult arterial endothelial cells also expressed multiple EFN and EPH genes. These results indicate that a wide variety of ephrins and Eph receptors might affect monocyte chemotaxis, contributing to the development of atherosclerosis. Their pathological significance requires further study.