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Thromb Haemost 1999; 82(02): 832-836
DOI: 10.1055/s-0037-1615919
Research Article
Schattauer GmbH

Regulation of Fibrinolysis in the Development of Atherothrombosis: Role of Adipose Tissue

I. Juhan-Vague
1   Lab. Haematology, CHU Timone, Marseille, FRANCE
,
M.C. Alessi
1   Lab. Haematology, CHU Timone, Marseille, FRANCE
› Author Affiliations
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Publication History

Publication Date:
09 December 2017 (online)

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Introduction

Among the list of coronary risk factors, it has recently been proposed that fibrinolytic system impairment, due to increased plasminogen activator inhibitor-1 (PAI-1) levels in plasma, could predict complications of atherosclerosis. The fibrinolytic system1 is regulated by a balance between activators and inhibitors. PAI-1, which inhibits t-PA and u-PA, is the main inhibitor of plasminogen activation. An increased PAI-1 concentration induces a reduction in plasmin formation and leads to fibrin accumulation.2-5 PAI-1 also induces changes in vessel wall remodeling through the activation of metalloproteinases and growth factors and the degradation of the extracellular matrix.4 In addition to its antiprotease activity, PAI-1 also participates in the cellular adhesion and migration processes. Because it binds to vitronectin in the same part of the molecule as vitronectin receptor or u-PA receptor, it mediates the release of cells from their substrate.6,7 All of these properties indicate that PAI-1 can be involved in tissue remodeling and thrombotic processes and, therefore, participates in the development of atherothrombosis.

In plasma, an elevated PAI-1 concentration is presently considered a risk factor for coronary vascular events. It appears that PAI-1 is an inducible target controlled for in insulin resistance and obesity, which are situations that favor the development of atherothrombosis. It has been postulated that PAI-1 could contribute to an increased susceptibility to atherothrombosis in insulin-resistant patients. The production of PAI-1 by adipose tissue has recently been demonstrated. The elucidation of the regulation of PAI-1 synthesis and the identification of factors responsible for increased plasma PAI-1 concentration in the insulin-resistant state might lead to therapeutic concepts for the prevention of atherothrombosis.

 

  • References

  • 1 Collen D, Lijnen HR. Basic and clinical aspects of fibrinolysis and thrombolysis. Blood 1991; 78: 3114-3124.
    PubMedGoogle Scholar
  • 2 Reilly CF, Fujita T, Hutzelmann JE, Mayer EJ, Shebuski RJ. Plasminogen activator inhibitor-1 suppresses endogenous fibrinolysis in a canine model of pulmonary embolism. Circulation 1991; 84: 287-292.
    CrossrefPubMedGoogle Scholar
  • 3 Erickson LA, Fici GJ, Lund JE, Boyle TP, Polites HG, Marotti KR. Development of venous occlusions in mice transgenic for the PAI-1 gene. Nature 1990; 346: 74-76.
    CrossrefPubMedGoogle Scholar
  • 4 Carmeliet P, Bouche A, De Clercq C, Janssen S, Pollefeyt S, Wyns S, Mulligan RC, Collen D. Biological effects of disruption of the tissue-type plasminogen activator, urokinase type plasminogen activator and plasminogen activator inhibitor-1 genes in mice. Ann NY Acad Sci 1995; 748: 367-382.
    PubMedGoogle Scholar
  • 5 Farrehi PM, Ozaki CK, Carmeliet P, Fay WP. Regulation of arterial thrombolysis by plasminogen activator inhibitor-1 in mice. Circulation 1998; 97: 1002-1008.
    CrossrefPubMedGoogle Scholar
  • 6 Stefansson S, Lawrence DA. The serpin PAI-1 inhibits cell migration by blocking integrin αvβ3 binding to vitronectin. Nature 1996; 323: 441-443.
    PubMedGoogle Scholar
  • 7 Deng G., Curriden SA, Wang S, Rosenberg S, Loskutoff DJ. Is plasminogen activator inhibitor 1 the molecular switch that governs urokinase receptor-mediated cell adhesion and release?. J Cell Biol 1996; 134: 1563-1571.
    CrossrefPubMedGoogle Scholar
  • 8 Juhan-Vague I, Alessi MC. Fibrinolysis and risk of coronary artery disease. Fibrinolysis 1996; 10: 127-136.
    PubMedGoogle Scholar
  • 9 Chandler WL, Alessi MC, Aillaud MF, Henderson P, Vague P. Juhan-Vague Clearance of t-PA and t-PA/PAI-1 complex: Relationship to elevated t-PA antigen in patients with high PAI-1 activity levels. Circulation 1997; 96: 761-768.
    CrossrefPubMedGoogle Scholar
  • 10 Meade TW, Ruddock V, Stirling Y, Chakrabarti T, Miller GJ. Fibrinolytic activity, clotting factors and long-term incidence of ischaemic heart disease in the Northwick Park Heart Study. Lancet 1993; 342: 1076-1079.
    CrossrefPubMedGoogle Scholar
  • 11 Ridker PM, Vaughan DE, Stampfer MJ, Manson JE, Hennekens CH. Endogenous tissue type plasminogen activator and risk of myocardial infarction. Lancet 1993; 341: 1165-1168.
    CrossrefPubMedGoogle Scholar
  • 12 Lowe GDO, Yarnell JWG, Sweetnam PM, Rumley A, Thomas HF, Elwood PC. Fibrin D-dimer, tissue plasminogen activator, plasminogen activator inhibitor, and the risk of major ischaemic heart disease in the Caerphilly Study. Thromb Haemost 1998; 79: 129-133.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Thogersen AM, Jansson JH, Boman K, Nilsson TK, Weinehall L, Huhtasaari F, Hallmans G. High plasminogen activator inhibitor and tissue plasminogen activator levels in plasma precede a first acute myocardial infarction in both men and women: Evidence for the fibrinolytic system as an independent primary risk factor. Circulation 1998; 98: 2241-2247.
    CrossrefPubMedGoogle Scholar
  • 14 Thompson SG, Kienast J, Pyke SDM, Haverkate F, van de Loo JCW. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. N Engl J Med 1995; 332: 635-641.
    CrossrefPubMedGoogle Scholar
  • 15 Juhan-Vague I, Pyke SDM, 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 Thrombosis and Disabilities Study. Circulation 1996; 94: 2057-2063.
    CrossrefPubMedGoogle Scholar
  • 16 Held C, Hjemdhal P, Rehnqvist N, Wallén NH, Björkander I, Ericksson SV, Forslund L, Wiman B. Fibrinolytic variables and cardiovascular prognosis in patients with stable angina pectoris treated with Verapamil or Metoprobol. Circulation 1997; 95: 2380-2386.
    CrossrefPubMedGoogle Scholar
  • 17 Juhan-Vague I, Alessi MC, Vague P. Increased plasma plasminogen activator inhibitor 1 levels. A possible link between insulin resistance and atherothrombosis. Diabetologia 1991; 34: 457-462.
    CrossrefPubMedGoogle Scholar
  • 18 Juhan-Vague I, Alessi MC, Joly P, Thirion X, Vague P, Declerck PJ, Serradimigni A, Collen D. Plasma plasminogen activator inhibitor 1 in angina pectoris: influence of plasma insulin and acute-phase response. Arteriosclerosis 1989; 9: 362-367.
    CrossrefPubMedGoogle Scholar
  • 19 Potter van Loon BJ, Kluft C, Radder JK, Blankenstein MA, Meinders AE. The cardiovascular risk factor plasminogen activator inhibitor type 1 is related to insulin resistance. Metabolism 1993; 42: 945-949.
    CrossrefPubMedGoogle Scholar
  • 20 Vague P, Juhan-Vague I, Chabert V, Alessi MC, Atlan C. Fat distribution and plasminogen activator inhibitor activity in non diabetic obese women. Metabolism 1989; 38: 913-915.
    CrossrefPubMedGoogle Scholar
  • 21 Schneider DJ, Sobel BE. Augmentation of synthesis of plasminogen activator inhibitor type 1 by insulin and insulin-like growth factor type 1: implications for vascular disease by hyperinsulinemic states. Proc Natl Acad Sci USA. 1991; 88: 9959-9963.
    CrossrefPubMedGoogle Scholar
  • 22 Nagi DK, Hendra TJ, Ryle AJ, Cooper TM, Temple RC, Clark PMS, Schneider AE, Hales CN, Yudkin JS. The relationships of concentrations of insulin, intact proinsulin and 32-33 split proinsulin with cardiovascular risk factors in type 2 (non insulin dependent) diabetic subjects. Diabetologia 1990; 33: 532-537.
    CrossrefPubMedGoogle Scholar
  • 23 Bavenholm P, De Faire U, Landou C, Efendic S, Nilsson J, Wiman B, Hamsten A. Progression of coronary artery disease in young male post-infarction patients is linked to disturbances of carbohydrate and lipoprotein metabolism and to impaired fibrinolytic function. Eur Heart J 1998; 19: 402-410.
    CrossrefPubMedGoogle Scholar
  • 24 Haverkate F, Thompson SG, Duckert F. Haemostasis factors in Angina Pectoris: Relation to gender, age and acute-phase reaction. Thromb Haemost 1995; 73: 561-567.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Reaven G.M.. Banting lecture 1988: Role of insulin resistance in human disease. Diabetes 1988; 37: 1595-1607.
    CrossrefPubMedGoogle Scholar
  • 26 Eschwege E, Richard JL, Thibult N, Ducimetière P, Warnet JM, Claude JR, Rosselin GE. Coronary heart disease mortality in relation with diabetes, blood glucose and plasma insulin levels. The Paris Prospective Study, ten years later. Horm Metab Res 1985; 15: 41-46.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 27 Desprès JP, Lamarche B, Mauriège P, Cantin B, Dagenais GR, Moorjani S, Lupien PJ. Hyperinsulinemia as an independent risk factor for ischemic heart disease. N Engl J Med 1996; 334: 952-957.
    CrossrefPubMedGoogle Scholar
  • 28 Björntorp P. “Portal” adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis 1990; 10: 493-496.
    CrossrefPubMedGoogle Scholar
  • 29 Larsson B, Svärdsud DK, Welin L, Wilhelmsen L, Björntorp P, Tibbin G. Abdominal adipose tissue distribution, obesity and risk of cardiovascular disease and death: 13 year follow-up of participants in the study of men born in 1913. BMJ 1984; 288: 1401-1404.
    CrossrefPubMedGoogle Scholar
  • 30 Cigolini M, Targher G, Bergamo Andreis IA, Tonoli M, Agostino G, De Sandre G. Visceral fat accumulation and its relation to plasma hemostatic factors in healthy men. Arterioscler Thromb Vasc Biol 1996; 16: 368-374.
    CrossrefPubMedGoogle Scholar
  • 31 Janand-Delenne B., Chagnaud C., Raccah D., Alessi MC., Juhan-Vague I., Vague P. Visceral fat as a main determinant of plasminogen activator inhibitor 1 level in women. Int J Obes Relat Metab Disord 1998; 22: 312-317.
    CrossrefPubMedGoogle Scholar
  • 32 Eliasson M, Asplund K, Evrin PE, Lindahl B, Lundblad D. Hyperinsulinemia predicts low tissue plasminogen activator activity in a healthy population: the Northern Sweden MONICA Study. Metabolism 1994; 43: 1579-1586.
    CrossrefPubMedGoogle Scholar
  • 33 Mykkänen L, Rönnemaa T, Marniemi J, Haffner SM, Bergman R, Laakso M. Insulin sensitivity is not an independent determinant of plasma plasminogen activator inhibitor-1 activity. Arterioscler Thromb 1994; 14: 1264-1271.
    CrossrefPubMedGoogle Scholar
  • 34 Toft I, Bonaa KH, Ingebretsen OC, Nordoy A, Birkeland KI, Jenssen T. Gender Differences in the relationships between plasma plasminogen activator inhibitor-1 activity and factors linked to the insulin resistance syndrome in essential hypertension. Arterioscler Thromb Vasc Biol 1997; 17: 553-559.
    CrossrefPubMedGoogle Scholar
  • 35 Scarabin PY, Aillaud MF, Amouyel P, Evans A, Luc G, Ferrières J, Arveiler D, Juhan-Vague I. Associations of fibrinogen, factor VII and PAI-1 with baseline findings among 10,500 male participants in a prospective study of myocardial infarction: The PRIME Study. Prospective Epidemiological Study of Myocardial Infarction. Thromb Haemost 1998; 80: 749-756.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 36 Williams SK, Wang TF, Gastrillo R, Jarrell BE. Liposuction-derived human fat used for vascular graft sodding contains endothelial cells and not mesothelial cells as the major cell type. J Vasc Surg 1994; 19: 916-923.
    CrossrefPubMedGoogle Scholar
  • 37 Silverman KJ, Lund DP, Zetter BR, Lainey LL, Shahood JA, Freiman DG, Folkman J, Barger AC. Angiogenic activity of adipose tissue. Biochem Biophys Res Commun 1988; 153: 347-352.
    CrossrefPubMedGoogle Scholar
  • 38 Claffey KP, Wilkison WO, Spiegelman BM. Vascular endothelial growth factor: Regulation by cell differentiation and activated second messenger pathways. J Biol Chem 1992; 267: 16317-16322.
    PubMedGoogle Scholar
  • 39 Bouloumie A, Lafontan M, Busse R. Leptin, the product of Ob gene, promotes angiogenesis. Circ Res 1998; 83: 1059-1066.
    CrossrefPubMedGoogle Scholar
  • 40 Darimont C, Saint-Marc P, Ailhaud G, Negrel R. Modulation of vascular tone and glycerol levels measured by in situ microdialysis in rat adipose tissue. Am J Physiol 1996; 271: E631-E635.
    PubMedGoogle Scholar
  • 41 Levine JA, Jensen MD, Eberhardt NL, O’Brien T. Adipocyte macrophage colony stimulating factor is a mediator of adipose tissue growth. J Clin Invest 1998; 101: 1557-1564.
    CrossrefPubMedGoogle Scholar
  • 42 Negrel R, Gaillard D, Ailhaud G. Prostacyclin as a potent effector of adipose cell differentiation. Biochem J 1989; 257: 399-405.
    CrossrefPubMedGoogle Scholar
  • 43 Nougues J, Reyne Y, Barenton B, Chery T, Garandel V, Soriano J. Differentiation of adipocyte precursors in a serum-free medium is influenced by glucocorticoids and endogenously produced insulin-like growth factor-I. Int J Obes 1993; 17: 159-167.
    PubMedGoogle Scholar
  • 44 Rahimi N, Tremblay E, MacAdam L, Roberts A, Elliot B. Autocrine secretion of TGF-beta1 and TGF-beta2 by preadipocytes and adipocytes: a potent negative regulator of adipocyte differenciation and proliferation of mammary carcinoma cells. In Vitro Cell Dev Biol Anim 1998; 34: 412-420.
    CrossrefPubMedGoogle Scholar
  • 45 Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P. Recombinant mouse Ob protein: Evidence for a peripheral signal linking adiposity and central neural networks. Science 1995; 269: 546-549.
    CrossrefPubMedGoogle Scholar
  • 46 Sawdey MS, Loskutoff DJ. Regulation of murine type 1 plasminogen activator inhibitor gene expression in vivo; tissue specificity and induction by lipopolysaccharide, tumor necrosis factor-α, transforming growth factor-β. J Clin Invest 1991; 88: 1346-1353.
    CrossrefPubMedGoogle Scholar
  • 47 Samad F, Loskutoff DJ. Tissue distribution and regulation of plasminogen activator inhibitor-1 in obese mice. Mol Med 1996; 2: 568-582.
    PubMedGoogle Scholar
  • 48 Shimomura I, Funahashi T, Takahashi M, Maeda K, Kotani K, Nakamura T, Yamashita S, Miura M, Fukuda Y, Takemura K, Tokunaga K, Matsuzawa Y. Enhanced expression of PAI-1 in visceral fat: Possible contributor to vascular disease in obesity. Nat Med 1996; 2: 800-803.
    CrossrefPubMedGoogle Scholar
  • 49 Morange PE, Aubert J, Peiretti F, Vague P, Lijnen HR, Verdier M, Negrel R, Juhan-Vague I, Alessi MC. Glucocorticoids and insulin promote plasminogen activator inhibitor 1 production by human adipose tissue. Diabetes 1999; 48: 890-895.
    CrossrefPubMedGoogle Scholar
  • 50 Samad F, Yamamoto K, Loskutoff DJ. Distribution and regulation of plasminogen activator inhibitor-1 in murine adipose tissue in vivo. Induction by tumor necrosis factor-a and lipopolysaccharide. J Clin Invest 1996; 97: 37-46.
    CrossrefPubMedGoogle Scholar
  • 51 Lundgren CH, Brown SL, Nordt TK, Sobel BE, Satoshi F. Elaboration of type-1 plasminogen activator inhibitor from adipocytes: A potential pathogenetic link between obesity and cardiovascular disease. Circulation 1996; 93: 106-110.
    CrossrefPubMedGoogle Scholar
  • 52 Alessi MC, Peiretti F, Morange P, Henry M, Nalbone G, Juhan-Vague I. Production of plasminogen activator inhibitor 1 by human adipose tissue: possible link between visceral fat accumulation and vascular disease. Diabetes 1997; 46: 860-867.
    CrossrefPubMedGoogle Scholar
  • 53 Eriksson P, Reynisdottir S, Lönnqvist F, Stemme V, Hamsten A, Arner P. Adipose tissue secretion of plasminogen activator inhibitor-1 in non obese and obese individuals. Diabetologia 1998; 41: 65-71.
    CrossrefPubMedGoogle Scholar
  • 54 Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-α: Direct role of obesity-linked insulin resistance. Science 1993; 259: 87-91.
    CrossrefPubMedGoogle Scholar
  • 55 Xu H, Sethi JK, Uysal KT, Wiesbrock SM, Scheja LR, Hostamisligil GS. The transmembrane form of tumor necrosis factor alpha inhibits adipogenesis via tumor necrosis factor receptor 1. Int J Obes Relat Metab Disord 1998; 22: S31.
    PubMedGoogle Scholar
  • 56 Uysal KT, Wiesbrock SM, Marino MW, Hotamisligil GS. Protection from obesity-induced insulin resistance in mice lacking TNF-α function. Nature 1997; 389: 610-614.
    CrossrefPubMedGoogle Scholar
  • 57 Uysal KT, Wiesbrock SM, Hotamisligil GS. Functional analysis of tumor necrosis factor (TNF) receptors in TNF-alpha-mediated insulin resistance in genetic obesity. Endocrinology 1998; 139: 4832-4838.
    CrossrefPubMedGoogle Scholar
  • 58 Ventre J, Doebber T, Wu M, MacNaul K, Stevens K, Pasparakis M, Kollias G, Moller DE. Targeted disruption of the tumor necrosis factor-alpha gene: Metabolic consequences in obese and nonobese mice. Diabetes 1997; 46: 1526-1531.
    CrossrefPubMedGoogle Scholar
  • 59 Memon RA, Grunfeld C, Moser AH, Feingold KR. Tumor necrosis factor mediates the effects of endotoxin on cholesterol and triglyceride metabolism in mice. Endocrinology 1993; 132: 2246-2253.
    CrossrefPubMedGoogle Scholar
  • 60 Jovinge S, Hamsten A, Tornvall P, Proudler A, Bavenholm P, Ericsson CG, Godsland I, de Faire U, Nilsson J. Evidence for a role of tumor necrosis factor a in disturbances or triglyceride and glucose metabolism predisposing to coronary heart disease. Metabolism 1998; 47: 113-118.
    CrossrefPubMedGoogle Scholar
  • 61 Kern PA, Saghizadeh M, Ong JM, Bosh RJ, Deem R, Simsolo RB. The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase. J Clin Invest 1995; 95: 2111-2119.
    CrossrefPubMedGoogle Scholar
  • 62 Morange PE, Alessi MC, Verdier M, Casanova D., Magalon G, Juhan-Vague I. PAI-1 produced ex vivo by human adipose tissue is relevant to PAI-1 blood level. Possible contribution of local TNF-α and TGF-β. Arterioscler. Thromb Vasc Biol 1999; 19: 1361-1365.
    CrossrefPubMedGoogle Scholar
  • 63 Samad F, Yamamoto K, Pandey M, Loskutoff DJ. Elevated expression of transforming growth factor-beta in adipose tissue from obese mice. Mol Med 1997; 3: 37-48.
    PubMedGoogle Scholar
  • 64 Cloutier DE, Comerford SA, Hammer RE. Hepatic fibrosis, glomerulosclerosis, and a lipodystrophy-like syndrome in PEPCK-TGF-β1 transgenic mice. J Clin Invest 1997; 100: 2697-2713.
    CrossrefPubMedGoogle Scholar
  • 65 Hauner H, Entenmann G, Wabitsch M, Gaillard G, Ailhaud G, Negrel R, Pfeiffer E. Promoting effect of glucocorticoïds on the differentiation of human adipocyte precursor cells cultured in a chemically defined medium. J Clin Invest 1989; 84: 1663-1670.
    CrossrefPubMedGoogle Scholar
  • 66 Alessi MC, Juhan-Vague I, Kooistra T, Declerck 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.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 67 Kooistra T, Bosma PJ, Tons HAM, Van Den Berg AP, Meyer P, Princen HMG. Plasminogen activator inhibitor 1: Biosynthesis and mRNA level are increased by insulin in cultured human hepatocytes. Thromb Haemost 1989; 62: 723-728.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 68 Samad F, Loskutoff DJ. Tissue distribution and regulation of plasminogen activator inhibitor 1 in obese mice. Mol Med 1998; 2: 5-10.
    PubMedGoogle Scholar
  • 69 Raccah D, Lassmann-Vague V, Alessi MC, Juhan-Vague I, Vague P. Intraperitoneal insulin administration does not modify plasminogen activator inhibitor 1 levels in IDDM patients. Diabetes Care 1994; 17: 941-942.
    PubMedGoogle Scholar
  • 70 Partridge CA, Gerritsen ME. Dexamethasone increases the release of three 44 KD proteins immunologically related to plasminogen activator inhibitor-1 from human umbilical vein endothelial and rabbit coronary microvessel endothelial cells. Thromb Res 1990; 57: 139-154.
    CrossrefPubMedGoogle Scholar
  • 71 Oikarinen A, Hoyhtya M. Dexamethasone induced plasminogen activator inhibitor: characterization, purification, and preparation of monoclonal antibodies. Arch Dermatol Res 1990; 282: 153-158.
    CrossrefPubMedGoogle Scholar
  • 72 Heaton JH, Kathju S, Gelehter TD. Transcriptional and posttranscriptional regulation of type 1 plasminogen activator inhibitor and tissue-type plasminogen activator gene expression in HTC rat hepatoma cells by glucocorticoids and cyclic nucleotides. Mol Endocrinol 1992; 6: 53-60.
    PubMedGoogle Scholar
  • 73 Patrassi GM, Sartori MT, Viero ML, Scarano L, Boscaro M, Girolami A. The fibrinolytic potential in patients with Cushing’s disease: A clue to their hypercoagulable state. Blood Coagul Fibrinolysis 1992; 3: 789-793.
    CrossrefPubMedGoogle Scholar
  • 74 Patrassi GM, Sartori MT, Livi U, Casonato A, Danesin C, Vettore S, Girolami A. Impairment of fibrinolytic potential in long-term steroid treatment after heart transplantation. Transplantation. 1997; 64: 1610-1614.
    CrossrefPubMedGoogle Scholar
  • 75 Bujalska IJ, Kumar S, Stewart PM. Does central obesity reflect “Cushing’s disease of the omentum”?”. Lancet 1997; 349: 1210-1213.
    CrossrefPubMedGoogle Scholar
  • 76 Rebuffe-Scribe M, Brönnegard M, Nillson A, Eldh J, Gustafsson JA, Bjöntorp P. Steroid hormone receptors in human adipose tissue. J Clin Endocrinol Metab 1990; 71: 1215-1219.
    CrossrefPubMedGoogle Scholar
  • 77 Bruzdzinski CJ, Johnson MR, Goble CAQ, Winograd SS, Gelehrter TD. Mechanism of glucocorticoid induction of the rat plasminogen activator inhibitor-1 gene in HTC rat hepatoma cells : Identification of cis-acting regulatory elements. Mol Endocrinol 1993; 7: 1169-1177.
    PubMedGoogle Scholar
  • 78 Parrelli JM, Meisler N, Cutroneo KR. Identification of a glucocorticoid response element in the human transforming growth factor beta 1 gene promoter. Int J Biochem Cell Biol 1998; 30: 623-627.
    CrossrefPubMedGoogle Scholar