AORTIC CARBOXYPEPTIDASE-LIKE PROTEIN, A NOVEL PROTEIN WITH DISCOIDIN AND CARBOXYPEPTIDASE-LIKE DOMAINS, IS UP-REGULATED DURING VASCULAR SMOOTH-MUSCLE CELL-DIFFERENTIATION

Phenotypic modulation of vascular smooth muscle cells plays an importa nt role in the pathogenesis of arteriosclerosis, In a screen of protei ns expressed in human aortic smooth muscle cells, we identified a nove l gene product designated aortic carboxypeptidase-like protein (ACLP), The similar to 4-kilobase human cDNA and its mouse homologue encode 1 158 and 1128 amino acid proteins, respectively, that are 85% identical . ACLP is a nonnuclear protein that contains a signal peptide, a lysin e- and proline-rich Il-amino acid repeating motif, a discoidin-like do main, and a C-terminal domain with 39% identity to carboxypeptidase E, By Western blot analysis and in situ hybridization, we detected abund ant ACLP expression in the adult aorta. ACLP was expressed predominant ly in the smooth muscle cells of the adult mouse aorta but not in the adventitia or in several other tissues. In cultured mouse aortic smoot h muscle cells, ACLP mRNA and protein were up-regulated 2-3-fold after serum starvation. Using a recently developed neural crest cell to smo oth muscle cell in vitro differentiation system, we found that ACLP mR NA and protein were not expressed in neural crest cells but were up-re gulated dramatically with the differentiation of these cells. These re sults indicate that ACLP may play a role in differentiated vascular sm ooth muscle cells.