Increased blood plasminogen activator inhibitor-1 and intercellular adhesion molecule-1 as possible risk factors of atherosclerosis in Werner syndrome

Gerontology
S MuranoY Saito

Abstract

Werner syndrome is a rare premature aging syndrome accompanied by severe atherosclerosis. The etiology of atherosclerosis is suspected to be due to its complications, namely diabetes mellitus, hyperinsulinemia and hyperlipidemia. But from an autopsy case we found that some other risk factors may be involved in the mechanism of atherosclerosis in this syndrome. Previously we revealed that the plasminogen activator inhibitor-1 (PAI-1) gene was being overexpressed in skin fibroblasts from a patient with this syndrome. PAI-1 is a potent inhibitor of tissue plasminogen activator and a possible risk factor of atherosclerosis. This led us to assess the plasma concentration of PAI-1. Our working hypothesis was that the PAI-1 gene was upregulated or not fully suppressed in cells responsible for the production of PAI-1 in plasma as well as in fibroblasts. The results show a high concentration of plasma PAI-1. One of the well-known physiological substances that induce the PAI-1 gene is tumor necrosis factor-alpha, which also induces other possible risk factors of atherosclerosis, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1. We found the serum concentrations of ICAM-1 to be elevated in patients with thi...Continue Reading

Citations

Mar 4, 2008·BMC Cardiovascular Disorders·Elena CastroLuis I Angel-Chávez
Jun 4, 2010·Pharmaceuticals·Mark C BagleyDavid Kipling
Jan 16, 2010·DNA Repair·Marie L RossiVilhelm A Bohr
Mar 21, 2000·FEBS Letters·D XuT Finkel
Nov 18, 2020·Antioxidants & Redox Signaling·Lucie Aumailley, Michel Lebel

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