Hypercoagulable State Indicates an Additional Risk Factor for Atherosclerosis in Werner’s Syndrome

Summary

To assess the risk factors for atherosclerosis in Werner’s syndrome (WS), coagulation/fibrinolytic system parameters and lipid levels were investigated in 9 non-smoker patients with WS and compared with normal control values (N). The levels of thrombin antithrombin III complex (p <0.05), D-dimer (p <0.05), tissue plasminogen activator (p <0.005) and PA inhibitor 1 (p <0.01) were significantly increased, while the level of thrombomodulin (p <0.005) in the fasting plasma was significantly decreased in the WS cases compared with N. Lipid profiles confirmed that 8 of the 9 patients were of hyperlipidemia type II_b, 7 had hyperinsulinemia and 5 fulfilled the criteria for clinical diabetes mellitus. The hypercoagulable condition suggested the existence of multiple risk factors for atherosclerosis in WS in addition to the previously reported hyperinsulinemia and hyperlipidemia.

• References

• 1 Epstein CJ, Martin GM, Schulttz AL, Motulsky AG. Werner’s syndrome: A review of its symptomatology, natural history, pathologic factors, genetics and relationship to the natural aging process. Medicine 1966; 45: 177-221
• 2 Goto M, Takeuchi F, Tanimoto K, Miyamoto T. Clinical, demographic and genetic aspects of Werner's syndrome in Japan. In: Werner's syndrome and human aging. Salk D, Fujiwara Y, Martin GM. eds New York: Plenum Press; 1985. pp 245-261
• 3 Goto M, Horiuchi Y, Tanimoto K, Ishii T, Nakashima N. Werner’s syndrome. J Am Geriatr Soc 1978; 26: 341-347
• 4 Goto M. Werner’s syndrome. In: Neurocutaneous Diseases. Gometz MR. ed New York: Butterworth Publishing; 1987. pp 241-246
• 5 Sato K, Goto M, Nishioka K. Werner’s syndrome associated with malignancies. Gerontol 1988; 34: 212-218
• 6 Goto M, Rubenstein M, Weber J, Woods K, Drayna D. Genetic linkage of Werner’s syndrome to five markers on chromosome 8. Nature 1992; 355: 735-738
• 7 Kikumoto R, Tamao Y, Ohkubo K, Tezuka T, Tonomura S. Thrombin inhibitors. 3. Carboxy-containing amide derivatives of N^a-substituted L-arginine. J Med Chem 1980; 23: 1293-1299
• 8 Goto M, Tanimoto K, Horiuchi Y, Sasazuki T. Family analysis of Werner’s syndrome. Clin Genet 1981; 19: 8-15
• 9 Kario K, Matsuo T, Kobayashi H. Which factors affect high D-dimer levels in the elderly. Thromb Res 1991; 62: 501-508
• 10 Asakura H. Levels of thrombin-antithrombin III complex in plasma in cases of acute promyelocytic leukemia. Thromb Res 1988; 50: 895-899
• 11 Holvoet P, De Boer A, Verstreken M, Collen D. An enzyme-linked immunosorbent assay (ELISA) for the measurement of plasmin-alpha₂-antiplas- min complex in human plasma. Application to the detection of in vivo activation of the fibrinolytic system Thromb Haemost 1986; 56: 124-127
• 12 Takada Y. Plasma levels of t-PA, free PAI-1 and a complex of t-PA with PAI-1 in human males and females at various ages. Thromb Res 1989; 55: 601-609
• 13 Ishii H, Nakano M, Tsubouchi J. et al Establishment of enzyme immunoassay of human thrombomodulin in plasma and urine using monoclonal antibodies. Thromb Haemost 1990; 63: 157-162
• 14 Alessi MC, Juhan-Vague I, Kooistra T, Declerk PJ, Collen D. Insulin stimulates the synthesis of plasminogen activator inhibitor 1 by the human hepatocellular cell line Hep G2. Thromb Haemost 1988; 60: 491-494
• 15 Ross R. The pathogenesis of atherosclerosis: a perspective for 1990s. Nature 1993; 362: 801-808
• 16 Murano S, Thweatt R, Shmokler Reis RJ, Jones RA, Moerman EJ, Goldstein S. Diverse gene sequences are overexpressed in Werner’s syndrome fibroblasts undergoing premature replicative senescence. Mol Cell Biol 1991; 11: 3905-3914
• 17 Goldstein S, Niewiarowski S. Increased procoagulant activity in cultured fibroblasts from progeria and Werner’s syndrome of premature ageing. Nature 1976; 260: 711-713
• 18 Thomas W, Rubenstein M, Goto M, Drayna D. A genetic analysis of the Werner’s syndrome region on human chromosome 8p. Genomics 1993; 16: 685-690