Download PDF
Thromb Haemost 1997; 78(06): 1495-1499
DOI: 10.1055/s-0038-1665440
Rapid Communication
Schattauer GmbH Stuttgart

Small, Dense LDL Particle Concentration Correlates with Plasminogen Activator Inhibitor Type-1 (PAI-1) Activity

Sari Väisänen
1   The Kuopio Research Institute of Exercise Medicine and Department of Physiology, Kuopio University, Finland
,
Manfred W Baumstark
2   Department of Rehabilitation, Prevention and Sports Medicine, Freiburg University, Germany
,
Ilkka Penttilä
3   Department of Clinical Chemistry, Kuopio University Hospital, Finland
,
Claude Bouchard
4   Physical Activity Sciences Laboratory, Laval University, Ste-Foy, Québec, Canada
,
Pirjo Halonen
5   Computing Centre, Kuopio University, Finland
,
Tuomo Rankinen
1   The Kuopio Research Institute of Exercise Medicine and Department of Physiology, Kuopio University, Finland
,
Aloys Berg
2   Department of Rehabilitation, Prevention and Sports Medicine, Freiburg University, Germany
,
Rainer Rauramaa
1   The Kuopio Research Institute of Exercise Medicine and Department of Physiology, Kuopio University, Finland
› Author Affiliations
Further Information

Publication History

Received 04 1997

Accepted after revision 16 July 1997

Publication Date:
12 July 2018 (online)

Also available at
  PDF Download  Permissions and Reprints

Summary

The relation between LDL subtractions and fibrinolytic activity was studied in 150 men aged 53 to 63 years. Apolipoprotein B (apoB) concentration in the most dense LDL-5 (r = 0.39, p <0.001) and LDL-6 (r = 0.43, p <0.001) subtractions associated with plasminogen activator inhibitor type-1 (PAI-1) activity. Subjects in the highest LDL-6 apoB tortile had higher PAI-1 (24.7 vs. 13.1 AU/ml, p <0.001) and lower t-PA (0.26 vs. 0.54 IU/ml, p <0.001) activities than men in the lowest tortile. The difference in PAI-1 remained after adjusting for either triglycerides (p = 0.039) or insulin (p = 0.015) with cardiorespiratory fitness as an additional covariate, and history of cardiovascular disease and smoking as factors. In a regression analysis, plasma insulin and LDL-6 apoB, but not plasma triglycerides and body mass index, entered the model, and explained 30.6 and 3.9 % of the variance in PAI-1 activity, respectively. The novel finding of the present study was the independent association between small, dense LDL particles and PAI-1 activity in middle-aged men.

 

  • References

  • 1 Shen MMS, Krauss RM, Lindgren FT, Forte TM. Heterogeneity of serum low density lipoproteins in normal human subjects. J Lipid Res 1981; 22: 236-244
    PubMedGoogle Scholar
  • 2 Krauss RM. Low density lipoprotein imbalances and risk of coronary artery disease. Curr Opin Lipidol 1991; 2: 248-252
    CrossrefPubMedGoogle Scholar
  • 3 Nigon F, Lesnik P, Rouis M, Chapman MJ. Discrete subspecies of human low density lipoproteins are heterogeneous in their interaction with the cellular LDL receptor. J Lipid Res 1991; 32: 1741-1753
    PubMedGoogle Scholar
  • 4 Tomvall P, Karpe F, Carlson LA, Hamsten A. Relationships of low density lipoprotein subfractions to angiographically defined coronary artery disease in young survivors of myocardial infarction. Atherosclerosis 1991; 90: 67-80
    CrossrefPubMedGoogle Scholar
  • 5 Griffin BA, Freeman DJ, Tait GW, Thomson J, Caslake MJ, Packard CJ, Shepherd J. Role of plasma triglyceride in the regulation of plasma low density lipoprotein (LDL) subfractions: relative contribution of small dense LDL to coronary heart disease risk. Atherosclerosis 1994; 106: 241-253
    CrossrefPubMedGoogle Scholar
  • 6 Katzel LI, Krauss RM, Goldberg AP. Relations of plasma TG and HDL-C concentrations to body composition and plasma insulin levels are altered in men with small LDL particles. Arterioscler Thromb 1994; 14: 1121-1128
    CrossrefPubMedGoogle Scholar
  • 7 Griffin BA, Packard CJ. Metabolism of VLDL and LDL subclasses. Curr Opin Lipidol 1994; 5: 200-206
    CrossrefPubMedGoogle Scholar
  • 8 Tan CE, Forster L, Caslake MJ, Bedford D, Watson TDG, McConnell M, Packard CJ, Shepherd J. Relations between plasma lipids and postheparin plasma lipases and VLDL and LDL subfraction patterns in normolipemic men and women. Arterioscler Thromb Vase Biol 1995; 15: 1839-1848
    CrossrefPubMedGoogle Scholar
  • 9 Watson TDG, Caslake MJ, Freeman DJ, Griffin BA, Hinnie J, Packard CJ, Shepherd J. Determinants of LDL subfraction distribution and concentrations in young normolipidemic subjects. Arterioscler Thromb 1994; 14: 902-910
    CrossrefPubMedGoogle Scholar
  • 10 Frayn KN. Insulin resistance and lipid metabolism. Curr Opin Lipidol 1993; 4: 197-204
    CrossrefPubMedGoogle Scholar
  • 11 Krauss RM, Rotter JI, Lusis AJ. Genetic and metabolic influences on LDL subclasses. In: Atherosclerosis X Woodford FP, Davignon J, Sniderman A. eds Elsevier Science B.V.. Amsterdam; The Netherlands: 1995. pp 980-983
    Google Scholar
  • 12 Campos H, Arnold KS, Balestra ME, Innerarity TL, Krauss RM. Differences in receptor binding of LDL subfractions. Arterioscler Thromb Vase Biol 1996; 16: 794-801
    CrossrefPubMedGoogle Scholar
  • 13 Tribble DL, Thiel PM, van denBerg JJM, Krauss RM. Differing a-tocopherol oxidative lability and ascorbic acid sparing effects in buoyant and dense LDL. Arterioscler Thromb Vase Biol 1995; 15: 2025-2031
    CrossrefPubMedGoogle Scholar
  • 14 Cortellaro M, Cofrancesco E, Boschetti C, Mussoni L, Donati MB, Cardillo M, Catalano M, Gabrielli L, Lombardi B, Specchia G, Tavazzi L, Tremoli E, Pozzoli E, Turri M. Increased fibrin turnover and high PAI-1 activity as predictors of ischemic events in atherosclerotic patients. A case-control study. Arterioscler Thromb 1993; 13: 1412-1417
    CrossrefPubMedGoogle Scholar
  • 15 Lupu F, Bergonzelli GE, Heim DA, Cousin E, Genton CY, Bachmann F, Kruithof EKO. Localization and production of plasminogen activator inhibitor-1 in human healthy and atherosclerotic arteries. Arterioscler Thromb 1993; 13: 090-100
    CrossrefPubMedGoogle Scholar
  • 16 Salomaa V, Stinson V, Kark JD, Folsom AR, Davis CE, Wu KK. Association of fibrinolytic parameters with early atherosclerosis. The ARIC Study. Atherosclerosis Risk in Communities Study. Circulation 1995; 91: 284-290
    CrossrefPubMedGoogle Scholar
  • 17 Juhan-Vague I, Pyke SD, Alessi MC, Jespersen J, Haverkate F, Thompson SG. Fibrinolytic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. ECAT Study Group. European Concerted Action on Thrombosis and Disabilities. Circulation 1996; 94: 2057-2063
    CrossrefPubMedGoogle Scholar
  • 18 Mussoni L, Mannucci L, Sirtori M, Camera M, Madema P, Sironi L, Tremoli E. Hypertriglyceridemia and regulation of fibrinolytic activity. Arterioscler Thromb 1992; 12: 19-27
    CrossrefPubMedGoogle Scholar
  • 19 Sironi L, Mussoni L, Prati L, Baldassarre D, Camera M, Banfi C, Tremoli E. Plasminogen activator inhibitor type-1 synthesis and mRNA expression in HepG2 cells are regulated by VLDL. Arterioscler Thromb Vase Biol 1996; 16: 89-96
    CrossrefPubMedGoogle Scholar
  • 20 Latron Y, Chautan M, Anfosso F, Alessi MC, Nalbone G, Lafont H, Juhan-Vague I. Stimulating effect of oxidized low density lipoproteins on plasminogen activator inhibitor-1 synthesis by endothelial cells. Arterioscler Thromb 1991; 11: 1821-1829
    CrossrefPubMedGoogle Scholar
  • 21 Tremoli E, Camera M, Madema P, Sironi L, Prati L, Colli S, Piovella F, Bernini F, Corsini A, Mussoni L. Increased synthesis of plasminogen activator inhibitor-1 by cultured human endothelial cells exposed to native and modified LDLs. An LDL receptor-independent phenomenon. Arterioscler Thromb 1993; 13: 338-346
    CrossrefPubMedGoogle Scholar
  • 22 Etingin OR, Hajjar DP, Hajjar KA, Harpel PC, Nachman RL. Lipoprotein (a) regulates plasminogen activator inhibitor-1 expression in endothelial cells: A potential mechanism in thrombogenesis. J Biol Chem 1991; 266: 2459-2465
    PubMedGoogle Scholar
  • 23 Fattal PG, Schneider DJ, Sobel BE, Billadello JJ. Post transcriptional regulation of expression of plasminogen activator inhibitor type 1 mRNA by insulin and insulin-like growth factor 1. J Biol Chem 1992; 267: 12412-12415
    PubMedGoogle Scholar
  • 24 Rauramaa R, Väisänen S, Mercuri M, Rankinen T, Penttilä I, Bond MG. Association of risk factors and body iron status to carotid atherosclerosis in middle-aged Eastern Finnish men. Eur Heart J 1994; 15: 1020-1027
    CrossrefPubMedGoogle Scholar
  • 25 Rauramaa R, Rankinen T, Tuomainen P, Väisänen S, Mercuri M. Inverse relationship between cardiorespiratory fitness and carotid atherosclerosis. Atherosclerosis 1995; 112: 213-221
    CrossrefPubMedGoogle Scholar
  • 26 Lindgren FT. Preparative ultracentrifugal laboratory procedures and suggestions for lipoprotein analysis. In: Analysis of Lipids and Lipoproteins Perkins EG. (ed) Champaign, IL; American Oil Chemists’ Society: 1975. pp 204-224
    Google Scholar
  • 27 Baumstark MW, Kreutz W, Berg A, Frey I, Keul J. Structure of human low-density lipoprotein subfractions determined by x-ray small-angle scattering. Biochim Biophys Acta 1990; 1037: 48-57
    CrossrefPubMedGoogle Scholar
  • 28 Mansfield MW, Stickland MH, Grant PJ. Environmental and genetic factors in relation to elevated circulating levels of plasminogen activator inhibitor-1 in Caucasian patients with non-insulin-dependent diabetes mellitus. Thromb Haemost 1995; 74: 842-847
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Galeano NF, Rumsey SC, Kwiterovich Jr P, Preud’Homme D, Marcel Y, Milne R, Walsh MT, Deckelbaum RJ. LDL particle size: effects on apoprotein B structure receptor recognition and atherosclerosis. In: Atherosclerosis X. Woodford FP, Davignon J, Sniderman A. eds Elsevier Science B.V.. Amsterdam; The Netherlands: 1995. pp 91-94
    Google Scholar
  • 30 Robbie LA, Booth NA, Brown PAJ, Bennett B. Inhibitors of fibrinolysis are elevated in atherosclerotic plaque. Arterioscler Thromb Vase Biol 1996; 16: 539-545
    CrossrefPubMedGoogle Scholar
  • 31 Kluft C, Verheijen JH. Leiden fibrinolysis working party: blood collection and handling procedures for assessment of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1). Fibrinolysis 1990; 4 (Suppl. 02) 155-161
    PubMedGoogle Scholar
  • 32 Juhan-Vague I, Alessi MC, Vague P. Thrombogenic and fibrinolytic factors and cardiovascular risk in non-insulin-dependent diabetes mellitus. Ann Med 1996; 28: 371-380
    PubMedGoogle Scholar
  • 33 Berg A, Halle M, Baumstark MW, Frey I, Keul J. Physical activity lipids and lipoprotein metabolism. The benefit of exercise and training in hyper-lipidemia. In: Exercise and disease. Watson RR, Eisinger M. (eds.) CRC Press: Boca Raton; 1992. pp 26-36
    Google Scholar
  • 34 Baumstark MW, Frey I, Berg A. Acute and delayed effects of prolonged exercise on serum lipoproteins. II. Concentration and composition of low-density lipoprotein subfractions and very low-density lipoproteins. Eur JAppl Physiol 1993; 66: 526-530
    PubMedGoogle Scholar
  • 35 Williams PT, Krauss RM, Vranizan KM, Wood PDS. Changes in lipoprotein subfractions during diet-induced and exercise-induced weight loss in moderately overweight men. Circulation 1990; 81: 1293-1304
    CrossrefPubMedGoogle Scholar
  • 36 Huttunen JK, Lansimies E, Voutilainen E, Ehnholm C, Hietanen E, Penttila I, Siitonen O, Rauramaa R. Effect of moderate physical exercise on serum lipoproteins. A controlled clinical trial with special reference to serum high-density lipoproteins. Circulation 1979; 60: 1220-1229
    CrossrefPubMedGoogle Scholar
  • 37 Rauramaa R, Salonen JT, Kukkonen-Haijula K, Seppänen K, Seppälä E, Vapaatalo H, Huttunen JK. Effects of mild physical exercise on serum lipoproteins and metabolites of arachidonic acid: A controlled randomised trial in middle-aged men. BMJ 1984; 288: 603-606
    CrossrefPubMedGoogle Scholar
  • 38 Gris J-C, Schved J-F, Feugeas O, Aguilar-Martinez P, Amaud A, Sanchez N, Sarlat C. Impact of smoking physical training and weight reduction on FVII PAI-1 and hemostatic markers in sedentary men. Thromb Haemost 1990; 64: 516-520
    Article in Thieme ConnectPubMedGoogle Scholar
  • 39 Stratton JR, Chandler WL, Schwartz RS, Cerqueira MD, Levy WC, Kahn SE, Larson VG, Cain KC, Beard JC, Abrass IB. Effects of physical conditioning on fibrinolytic variables and fibrinogen in young and old healthy adults. Circulation 1991; 83: 1692-1697
    CrossrefPubMedGoogle Scholar
  • 40 Rankinen T, Rauramaa R, Väisänen S, Penttila IM, Uusitupa M. Relation of habitual diet and cardiorespiratory fitness to blood coagulation and fibrinolytic factors. Thromb Haemost 1994; 71: 180-183
    Article in Thieme ConnectPubMedGoogle Scholar
  • 41 Stevenson ET, Davy KP, Seals DR. Hemostatic, metabolic, and androgenic risk factors for coronary heart disease in physically active and less active postmenopausal women. Arterioscler Thromb Vase Biol 1995; 15: 669-677
    CrossrefPubMedGoogle Scholar