RGD Reference Report - Urokinase plasminogen activator in injured adventitia increases the number of myofibroblasts and augments early proliferation. - Rat Genome Database

RGD Reference Report - Urokinase plasminogen activator in injured adventitia increases the number of myofibroblasts and augments early proliferation. - Rat Genome Database

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Urokinase plasminogen activator in injured adventitia increases the number of myofibroblasts and augments early proliferation.
Authors:	Plekhanova, OS Stepanova, VV Ratner, EI Bobik, A Tkachuk, VA Parfyonova, YV
Citation:	Plekhanova OS, etal., J Vasc Res. 2006;43(5):437-46. Epub 2006 Aug 7.
RGD ID:	6484216
Pubmed:	PMID:16899994 (View Abstract at PubMed)
DOI:	DOI:10.1159/000094906 (Journal Full-text)
Myofibroblasts are involved in vessel remodeling during the development of hypertension as well as after angioplasty and aortocoronary grafting, but the mechanisms of myofibroblastic phenotypic modulation are not fully elucidated. We assessed the role of urokinase plasminogen activator (uPA) and its proteolytic activity in myofibroblast differentiation and the early proliferation following mechanical injury of the rat carotid adventitia. The effects of perivascular application of recombinant uPA (r-uPA), proteolytically inactive r-uPA(H/Q) and uPA neutralizing antibody were evaluated 4 days after surgical injury to the adventitia. The phenotype of adventitial cells was assessed using anti-alpha-smooth muscle actin (alpha-SM actin) antibody, anti-SM heavy chain myosin, anti-high-molecular-weight caldesmon, anti-smoothelin and anti-ED-1 antibodies, proliferation by the expression of proliferating cell nuclear antigen, and the size of the adventitia by quantitative morphometry. Four days after injury, the intensive immunostaining for urokinase appeared in the rat carotid artery adventitia. At the same time, the frequency of alpha-SM actin-positive adventitial cells was 1.8+/-1.1% in uninjured arteries and 25.2+/-5.4% in injured arteries (p<0.05), and the respective frequency of ED-1-positive cells 1.5+/-1.1 and 25.0+/-5.2%. The application of exogenous r-uPA doubled the numbers of alpha-SM actin-positive adventitial cells to 55.7+/-6.8% (p<0.05). ED-1-positive cells and proliferating cell nuclear antigen-positive cells as well as the size of the adventitia were also significantly increased after r-uPA compared with injury alone. In contrast, the proteolytically inactive r-uPA(H/Q) did not affect any parameters. The application of uPA neutralizing antibody attenuated the frequency of alpha-SM actin-positive cells to 12.6+/-3.5% (p<0.05), the frequency of ED-1-positive cells, and the numbers of adventitial cells. r-uPA stimulation of cultured human skin fibroblasts significantly increased the alpha-SM actin content in a concentration-dependent manner. In contrast, r-uPAH/Q did not induce changes in alpha-SM actin content. We conclude that uPA, which is upregulated in the injured adventitia, can augment adventitial cell accumulation, including myofibroblasts, and adventitia growth early after injury of the rat carotid artery adventitia by mechanisms involving proteolysis.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
positive regulation of cell population proliferation		IMP		6484216		RGD

Objects Annotated

Genes (Rattus norvegicus)

Plau (plasminogen activator, urokinase)

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