Lipopolysaccharide-induced plasma PAI-1 increase does not correlate with PAI-1 synthesised de novo in the liver

Abstract

Plasminogen activator inhibitor-1 (PAI-1) is the primary physiological inhibitor of tissue type plasminogen activator (t-PA) [ [1] Alessi M.C. Juhan-Vague I. PAI-1 and the metabolic syndrome: links, causes, and consequences. Arterioscler Thromb Vasc Biol. 2006; 26: 2200-2207 Crossref PubMed Scopus (287) Google Scholar ]. High levels of plasma PAI-1 disrupt the fibrinolytic system to create a prothrombotic state that is associated with the development of pathological conditions such as thrombosis, fibrosis and cardiovascular diseases [ [1] Alessi M.C. Juhan-Vague I. PAI-1 and the metabolic syndrome: links, causes, and consequences. Arterioscler Thromb Vasc Biol. 2006; 26: 2200-2207 Crossref PubMed Scopus (287) Google Scholar ]. Although the source of plasma PAI-1 under normal conditions and its increase in plasma under pathological conditions have been discussed, the source nevertheless remains obscure. Adipose tissue is generally considered the most likely contributor to elevated plasma PAI-1 under conditions of obesity [ [1] Alessi M.C. Juhan-Vague I. PAI-1 and the metabolic syndrome: links, causes, and consequences. Arterioscler Thromb Vasc Biol. 2006; 26: 2200-2207 Crossref PubMed Scopus (287) Google Scholar ]. However, the liver is also an important contributor to the increase in plasma PAI-1 in obesity [ 2 Alessi M.C. Bastelica D. Mavri A. Morange P. Berthet B. Grino M. et al. Plasma PAI-1 levels are more strongly related to liver steatosis than to adipose tissue accumulation. Arterioscler Thromb Vasc Biol. 2003; 23: 1262-1268 Crossref PubMed Scopus (153) Google Scholar , 3 Oishi K. Ohkura N. Wakabayashi M. Shirai H. Sato K. Matsuda J. et al. CLOCK is involved in obesity-induced disordered fibrinolysis in ob/ob mice by regulating PAI-1 gene expression. J Thromb Haemost. 2006; 4: 1774-1780 Crossref PubMed Scopus (79) Google Scholar , 4 Oishi K. Ohkura N. Matsuda J. Ishida N. Food deprivation induces adipose plasminogen activator inhibitor-1 (PAI-1) expression without accumulation of plasma PAI-1 in genetically obese and diabetic db/db mice. Thromb Haemost. 2007; 98: 864-870 PubMed Google Scholar ]. We have also shown that plasma PAI-1 levels are intricately associated with PAI-1 produced by the liver [ [5] Ohkura N. Shirakura M. Nakatani E. Oishi K. Atsumi G.-I. Associations between PAI-1 expression in various organs and its plasma concentrations in obese model mice. Thromb Res. 2012; 130: e301-e304 Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar ].