title: Expression of fibrinolytic genes in tissues from human atherosclerotic aneurysms and from obese mice.
abstract: The disturbances in the balance of pro- and antifibrinolytic activity, as observed in AAA and obesity, respectively, have considerable potential for influencing both intra- and extravascular fibrinolytic events and may be causally related to the development of vascular disease. For example, the wall of the aortic atherosclerotic aneurysm seems to host an uneven distribution and imbalanced expression of the various components of the fibrinolytic system. The sites of increased proteolytic activity may contribute to localized neovascularization and promote the rapid breakdown of ECM components, which result in mural weakening and eventual rupture of untreated aortic aneurysms. On the other hand, the disturbance of the normal hemostatic balance observed in obesity appears to result from the elevated expression of PAI-1 by the adipose tissue. Our data strongly suggest that the adipocyte is one of the primary cells in the adipose tissue capable of expressing PAI-1 both in obesity, and in response to cytokines and hormones like TNF-alpha and insulin. Since both TNF-alpha and insulin are known to increase in obesity, the elevated levels of PAI-1 observed in the plasma of obese individuals may result from TNF-alpha and/or insulin induction of PAI-1 in the adipose tissue itself.
authors.affiliation: Scripps Research Institute, Department of Vascular Biology, La Jolla, California 92037, USA.
authors.forename: F
authors.initials: F
authors.lastname: Samad
authors.forename: J
authors.initials: J
authors.lastname: Schneiderman
authors.forename: D
authors.initials: D
authors.lastname: Loskutoff
mesh_terms: D000783:Aneurysm; D000818:Animals; D001161:Arteriosclerosis / Q000097:blood / Q000235:genetics*; D005342:Fibrinolysis / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000097:blood / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*
chemical_list: D017395:Plasminogen Activator Inhibitor 1