We investigated whether vascular smooth muscle cells (VSMC)-derived from @entity1 produce angiotensin (Ang) II upon change from the contractile phenotype to the synthetic phenotype by incubation with fibronectin (FN). Expression of alpha-smooth muscle (SM) actin, apparent in the contractile phenotype, was decreased by FN. Expressions of matrix Gla and @entity1096 , apparent in the synthetic phenotype, were increased by FN. Ang II measured by radioimmunoassay (RIA) was significantly increased in @entity1 VSMC by FN. Expression of mRNAs for Ang II-generating proteases @entity10815 , @entity3921 , @entity1289 , and chymase was increased by FN. Expressions of @entity10815 and @entity3921 proteins were also increased by FN. Ang I-generating activity, which was inhibited by an aspartyl protease inhibitor @entity14622 , was readily detected in the conditioned medium from human VSMC. Antisense oligodeoxynucleotides (ODNs) that hybridize with @entity10815 and @entity3921 significantly inhibited FN-increased Ang II in conditioned medium and cell extracts. In VSMC conditioned medium, FN-induced elevation of Ang II was significantly inhibited by @entity29274 but not by chymostatin. Ang II type 1 receptor antagonist @entity1564 completely, and antisense @entity10815 and @entity3921 ODNs partially inhibited the FN-stimulated growth of @entity1 VSMC. These results indicate that the change of homogeneous cultures of @entity1 VSMC from the contractile to the synthetic phenotype sequentially increases expression of proteases @entity10815 , @entity3921 , and @entity1289 , production of Ang II and productions of growth factors, culminating in VSMC proliferation. These findings implicate a new mechanism for the pathogenesis of @entity1 vascular proliferative diseases.

XXXX -derived vascular smooth muscle cells produce angiotensin II by changing to the synthetic phenotype.

@entity1 :: ('9606', 'Species') :: ['human'] @entity10815 :: ('1509', 'Gene') :: ['cathepsin D'] @entity14622 :: ('MESH:C031375', 'Chemical') :: ['pepstatin A'] @entity1289 :: ('1636', 'Gene') :: ['ACE'] @entity29274 :: ('MESH:C055603', 'Chemical') :: ['temocapril'] @entity1564 :: ('MESH:C081643', 'Chemical') :: ['CV11974'] @entity1096 :: ('6696', 'Gene') :: ['osteopontin'] @entity3921 :: ('1511', 'Gene') :: ['cathepsin G']
@entity1 :: (9606,Species) :: ['Human']
