title: Fibronectin and lipoprotein(a) are inversely related to plasminogen activator inhibitor type-1 levels in Type 2 diabetic patients without complications.
abstract: Plasminogen activator inhibitor type-1 (PAI-1), the most important physiological fibrinolysis inhibitor, is considered an independent factor of cardiovascular risk in Type 2 diabetes mellitus (T2DM). In previous papers we demonstrated that a T2DM population without complications presents: 1) PAI-1 not increased with respect to a control group; and 2) a negative correlation between PAI-1 and lipoprotein(a) [Lp(a)], suggesting that in these subjects PAI-1 levels could be modulated by the "endothelial stress" induced by Lp(a) and diabetes. This work has been performed in order to better verify this intriguing hypothesis, and the endothelial stress has been evaluated through a marker of endothelial damage, fibronectin (FNC). For this purpose we chose a T2DM population without complications (n=73) and a control group (n=46). Plasma concentrations of FNC, Lp(a), PAI-1 antigen and activity, and the main parameters of lipo- and glycometabolic balance were determined. Fibronectin was significantly higher in diabetics with respect to controls (p<0.01). As expected, significant correlation between PAI-1 antigen, PAI-1 activity and Lp(a) (r=-0.54,p<0.01 and r=-0.39,p<0.01, respectively) was found only in diabetic patients. In the same group FNC showed a significant correlation with PAI-1 antigen and activity (r=-0.49,p<0.01 and r=-0.47; p<0.01, respectively), while no relationship was found between Lp(a) and FNC. Multiple regression analysis showed statistically significant correlation between PAI-1 antigen and PAI-1 activity with FNC and Lp(a) in diabetic patients without complications (p<0.05). These data suggest that in absence of complications, the endothelium is able to modulate PAI-1 levels, favouring in that way the fibrinolytic pathway and, subsequently, the recovery of the endothelial integrity. This modulation seems to be related to parameters such as Lp(a) and FNC, although the mechanisms of the endothelial stress of these two molecules seem to be different.
authors: Department of Gerontological Research, Centre of Biochemistry, INRCA, Ancona, Italy.
authors: R
authors: R
authors: Testa
authors: A R
authors: AR
authors: Bonfigli
authors: C
authors: C
authors: Sirolla
authors: G
authors: G
authors: De Grazia
authors: P
authors: P
authors: Compagnucci
authors: S
authors: S
authors: Manfrini
authors: D
authors: D
authors: Fumelli
authors: I
authors: I
authors: Testa
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D005353:Fibronectins / Q000097:blood*; D019270:Fructosamine / Q000097:blood; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood*; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D012016:Reference Values; D012044:Regression Analysis; D010959:Tissue Plasminogen Activator / Q000097:blood; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D002784:Cholesterol; D005353:Fibronectins; D019270:Fructosamine; D006442:Glycated Hemoglobin; D017270:Lipoprotein(a); D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator; D014280:Triglycerides