Can inactivators of plasminogen activator inhibitor alleviate the burden of obesity and diabetes? (Review)

International Journal of Molecular Medicine

Volumn 29, Issue 1, 2012, Pages 3-11

  Jankun, Jerzy ^a,b,c   Al Senaidy, Abdulrahman ^c   Skrzypczak Jankun, Ewa ^a  

^a MEDICAL COLLEGE OF OHIO   (United States)

^b MEDICAL UNIVERSITY OF GDANSK   (Poland)

^c KING SAUD UNIVERSITY   (Saudi Arabia)

Author keywords

Diabetes; Obesity; Plasminogen activator inhibitor

Indexed keywords

AMYLOID A PROTEIN; BLOOD CLOTTING FACTOR 7; C REACTIVE PROTEIN; CAFFEINE; FATTY ACID; FIBRINOGEN; HAPTOGLOBIN; HEAT SHOCK TRANSCRIPTION FACTOR 1; INTERLEUKIN 1BETA; INTERLEUKIN 6; PLASMIN; PLASMINOGEN ACTIVATOR INHIBITOR 1; S 35225; TIPLASININ; TRANSFORMING GROWTH FACTOR BETA; TRIACYLGLYCEROL; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; UROKINASE; UROKINASE RECEPTOR; VERY LOW DENSITY LIPOPROTEIN; VITRONECTIN; VON WILLEBRAND FACTOR; XR 5118;

ADIPOSE TISSUE; ALLELE; ANGIOGENESIS; BINDING AFFINITY; BODY MASS; CELL DIFFERENTIATION; CYTOKINE PRODUCTION; DIABETES MELLITUS; DIABETIC NEPHROPATHY; DISEASE COURSE; DNA POLYMORPHISM; DOWN REGULATION; DRUG BINDING; EXTRACELLULAR MATRIX; FIBRINOLYSIS; FLUID INTAKE; GENE MUTATION; GENE OVEREXPRESSION; GENETIC RISK; HUMAN; LIFESTYLE; LIFESTYLE MODIFICATION; NONHUMAN; NUTRITION; OBESITY; PATHOPHYSIOLOGY; PLASMINOGEN ACTIVATION; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; REVIEW; RISK FACTOR; VASCULARIZATION; VENOUS THROMBOEMBOLISM; WEIGHT REDUCTION;

ANIMALS; DIABETES MELLITUS; HUMANS; OBESITY; PLASMINOGEN ACTIVATOR INHIBITOR 1;

EID: 84855181132     PISSN: 11073756     EISSN: 1791244X     Source Type: Journal    
DOI: 10.3892/ijmm.2011.810     Document Type: Review

References (104)

1. Al-Baghli NA, Al-Ghamdi AJ, Al-Turki KA, Al Elq AH, El-Zubaier AG and Bahnassy A: Prevalence of diabetes mellitus and impaired fasting glucose levels in the Eastern Province of Saudi Arabia: results of a screening campaign. Singapore Med J 51: 923-930, 2010.
2. Alqurashi KA, Aljabri KS and Bokhari SA: Prevalence of diabetes mellitus in a Saudi community. Ann Saudi Med 31: 19-23, 2011.
3. Diabetes - a global threat (Editorial). Lancet 373: 1735, 2009.
4. Ginter E and Simko V: Diabetes type 2 pandemic in 21st century. Bratisl Lek Listy 111: 134-137, 2010.
5. Steinberger J and Daniels SR: Obesity, insulin resistance, diabetes, and cardiovascular risk in children: an American Heart Association scientific statement from the Atherosclerosis, Hypertension, and Obesity in the Young Committee (Council on Cardiovascular Disease in the Young) and the Diabetes Committee (Council on Nutrition, Physical Activity, and Metabolism). Circulation 107: 1448-1453, 2003. (Pubitemid 36350747)
6. Jankun J, Aleem AM, Selman SH, Basrur V and Skrzypczak- Jankun E: VLHL plasminogen activator inhibitor spontaneously reactivates from the latent to active form. Int J Mol Med 23: 57-63, 2009.
7. Jankun J, Aleem AM, Struniawski R, Lysiak-Szydlowska W, Selman SH and Skrzypczak-Jankun E: Accelerated thrombus lysis in the blood of plasminogen activator inhibitor deficient mice is inhibited by PAI-1 with a very long half-life. Pharmacol Rep 61: 673-680, 2009.
8. Jankun J and Skrzypczak-Jankun E: Yin and yang of the plasminogen activator inhibitor. Pol Arch Med Wewn 119: 410-417, 2009.
9. Swiercz R, Keck RW, Skrzypczak-Jankun E, Selman SH and Jankun J: Recombinant PAI-1 inhibits angiogenesis and reduces size of LNCaP prostate cancer xenografts in SCID mice. Oncol Rep 8: 463-470, 2001.
10. Iishi H, Tatsuta M, Baba M, Yano H, Uehara H and Nakaizumi A: Suppression by amiloride of bombesin-enhanced peritoneal metastasis of intestinal adenocarcinomas induced by azoxymethane. Int J Cancer 63: 716-719, 1995.
11. Kook YH, Adamski J, Zelent A and Ossowski L: The effect of antisense inhibition of urokinase receptor in human squamous cell carcinoma on malignancy. EMBO J 13: 3983-3991, 1994. (Pubitemid 24275853)
12. Ossowski L: In vivo invasion of modified chorioallantoic membrane by tumor cells: the role of cell surface-bound urokinase. J Cell Biol 107: 2437-2445, 1988.
13. Ossowski L: Invasion of connective tissue by human carcinoma cell lines: requirement for urokinase, urokinase receptor, and interstitial collagenase. Cancer Res 52: 6754-6760, 1992.
14. Berger DH: Plasmin/plasminogen system in colorectal cancer. World J Surg 26: 767-771, 2002.
15. Kwaan HC: The plasminogen-plasmin system in malignancy. Cancer Metastasis Rev 11: 291-311, 1992.
16. Kwaan HC and McMahon B: The role of plasminogen-plasmin system in cancer. Cancer Treat Res 148: 43-66, 2009.
17. Cortese K, Sahores M, Madsen CD, Tacchetti C and Blasi F: Clathrin and LRP-1-independent constitutive endocytosis and recycling of uPAR. PLoS One 3: e3730, 2008.
18. Czekay RP, Aertgeerts K, Curriden SA and Loskutoff DJ: Plasminogen activator inhibitor-1 detaches cells from extracellular matrices by inactivating integrins. J Cell Biol 160: 781-791, 2003. (Pubitemid 36298272)
19. Poliakov A, Tkachuk V, Ovchinnikova T, Potapenko N, Bagryantsev S and Stepanova V: Plasmin-dependent elimination of the growth-factor-like domain in urokinase causes its rapid cellular uptake and degradation. Biochem J 355: 639-645, 2001. (Pubitemid 32434080)
20. Berkenpas MB, Lawrence DA and Ginsburg D: Molecular evolution of plasminogen activator inhibitor-1 functional stability. EMBO J 14: 2969-2977, 1995.
21. Dawson SJ, Wiman B, Hamsten A, Green F, Humphries S and Henney AM: The two allele sequences of a common polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene respond differently to interleukin-1 in HepG2 cells. J Biol Chem 268: 10739-10745, 1993. (Pubitemid 23162248)
22. Wiklund PG, Nilsson L, Ardnor SN, et al.: Plasminogen activator inhibitor-1 4G/5G polymorphism and risk of stroke: replicated findings in two nested case-control studies based on independent cohorts. Stroke 36: 1661-1665, 2005. (Pubitemid 41098758)
23. Jankun J and Skrzypczak-Jankun E: Bleeding diathesis is associated with an A15T heterozygous mutation in exon 2 of the plasminogen activator inhibitor type 1. Exp Ther Med 1: 575-577, 2010.
24. Zhang ZY, Wang ZY, Dong NZ, Bai X, Zhang W and Ruan CG: A case of deficiency of plasma plasminogen activator inhibitor-1 related to Ala15Thr mutation in its signal peptide. Blood Coagul Fibrinolysis 16: 79-84, 2005.
25. Fay WP, Parker AC, Condrey LR and Shapiro AD: Human plasminogen activator inhibitor-1 (PAI-1) deficiency: characterization of a large kindred with a null mutation in the PAI-1 gene. Blood 90: 204-208, 1997. (Pubitemid 27276563)
26. Fay WP, Shapiro AD, Shih JL, Schleef RR and Ginsburg D: Brief report: complete deficiency of plasminogen-activator inhibitor type 1 due to a frame-shift mutation. N Engl J Med 327: 1729-1733, 1992.
27. Jankun J, Skotnicka M, Lysiak-Szydlowska W, Al-Senaidy A and Skrzypczak-Jankun E: Diverse inhibition of plasminogen activator inhibitor type 1 by theaflavins of black tea. Int J Mol Med 27: 525-529, 2011.
28. Chorostowska-Wynimko J, Swiercz R, Skrzypczak-Jankun E, Wojtowicz A, Selman SH and Jankun J: A novel form of the plasminogen activator inhibitor created by cysteine mutations extends its half-life: relevance to cancer and angiogenesis. Mol Cancer Ther 2: 19-28, 2003.
29. De Taeye B, Gils A and Declerck PJ: The story of the serpin plasminogen activator inhibitor 1: is there any need for another mutant? Thromb Haemost 92: 898-924, 2004. (Pubitemid 39545512)
30. Vleugels N, Leys J, Knockaert I and Declerck PJ: Effect of stabilizing versus destabilizing interactions on plasminogen activator inhibitor-1. J Pharm Belg 55: 57-58, 2000. (Pubitemid 30265903)
31. Tucker HM, Mottonen J, Goldsmith EJ and Gerard RD: Engineering of plasminogen activator inhibitor-1 to reduce the rate of latency transition. Nat Struct Biol 2: 442-445, 1995.
32. Stoop AA, Jespers L, Lasters I, Eldering E and Pannekoek H: High-density mutagenesis by combined DNA shuffling and phage display to assign essential amino acid residues in protein-protein interactions: application to study structure-function of plasminogen activation inhibitor 1 (PAI-I). J Mol Biol 301: 1135-1147, 2000.
33. Verstraete M: Newer thrombolytic agents. Ann Acad Med Singapore 28: 424-433, 1999.
34. Jankun J, Aleem AM, Specht Z, et al.: PAI-1 induces cell detachment, down-regulates nucleophosmin (B23) and fortilin (TCTP) in LnCAP prostate cancer cells. Int J Mol Med 20: 11-20, 2007.
35. Tuynder M, Fiucci G, Prieur S, et al.: Translationally controlled tumor protein is a target of tumor reversion. Proc Natl Acad Sci USA 101: 15364-15369, 2004. (Pubitemid 39441547)
36. Tuynder M, Susini L, Prieur S, et al.: Biological models and genes of tumor reversion: cellular reprogramming through tpt1/TCTP and SIAH-1. Proc Natl Acad Sci USA 99: 14976-14981, 2002. (Pubitemid 35334595)
37. Badawi A, Klip A, Haddad P, et al.: Type 2 diabetes mellitus and inflammation: prospects for biomarkers of risk and nutritional intervention. Diabetes Metab Syndr Obes 3: 173-186, 2010.
38. Birgel M, Gottschling-Zeller H, Rohrig K and Hauner H: Role of cytokines in the regulation of plasminogen activator inhibitor-1 expression and secretion in newly differentiated subcutaneous human adipocytes. Arterioscler Thromb Vasc Biol 20: 1682-1687, 2000. (Pubitemid 30353905)
39. Samad F and Loskutoff DJ: The fat mouse: a powerful genetic model to study elevated plasminogen activator inhibitor 1 in obesity/NIDDM. Thromb Haemost 78: 652-655, 1997. (Pubitemid 27289321)
40. Grant MB, Ellis EA, Caballero S and Mames RN: Plasminogen activator inhibitor-1 overexpression in nonproliferative diabetic retinopathy. Exp Eye Res 63: 233-244, 1996. (Pubitemid 26325113)
41. Kishore P, Li W, Tonelli J, et al.: Adipocyte-derived factors potentiate nutrient-induced production of plasminogen activator inhibitor-1 by macrophages. Sci Transl Med 2: 20ra15, 2010.
42. Venugopal J, Hanashiro K and Nagamine Y: Regulation of PAI-1 gene expression during adipogenesis. J Cell Biochem 101: 369-380, 2007. (Pubitemid 46698871)
43. Skurk T and Hauner H: Obesity and impaired fibrinolysis: role of adipose production of plasminogen activator inhibitor-1. Int J Obes Relat Metab Disord 28: 1357-1364, 2004. (Pubitemid 39481839)
44. Ma LJ, Mao SL, Taylor KL, et al.: Prevention of obesity and insulin resistance in mice lacking plasminogen activator inhibitor 1. Diabetes 53: 336-346, 2004. (Pubitemid 38174548)
45. Hoffstedt J, Andersson IL, Persson L, Isaksson B and Arner P: The common -675 4G/5G polymorphism in the plasminogen activator inhibitor -1 gene is strongly associated with obesity. Diabetologia 45: 584-587, 2002. (Pubitemid 34533839)
46. Stein PD and Goldman J: Obesity and thromboembolic disease. Clin Chest Med 30: 489-493, 2009.
47. Correia ML and Haynes WG: A role for plasminogen activator inhibitor-1 in obesity: from pie to PAI? Arterioscler Thromb Vasc Biol 26: 2183-2185, 2006. (Pubitemid 44465709)
48. Mavri A, Alessi MC, Bastelica D, et al.: Subcutaneous abdominal, but not femoral fat expression of plasminogen activator inhibitor-1 (PAI-1) is related to plasma PAI-1 levels and insulin resistance and decreases after weight loss. Diabetologia 44: 2025-2031, 2001. (Pubitemid 33124048)
49. Crandall DL, Quinet EM, El Ayachi S, et al.: Modulation of adipose tissue development by pharmacological inhibition of PAI-1. Arterioscler Thromb Vasc Biol 26: 2209-2215, 2006. (Pubitemid 44465713)
50. Loktionov A, Bingham SA, Vorster H, Jerling JC, Runswick SA and Cummings JH: Apolipoprotein E genotype modulates the effect of black tea drinking on blood lipids and blood coagulation factors: a pilot study. Br J Nutr 79: 133-139, 1998. (Pubitemid 28081863)
51. Skrzypczak-Jankun E and Jankun J: Theaflavin digallate inactivates plasminogen activator inhibitor: could tea help in Alzheimer's disease and obesity? Int J Mol Med 26: 45-50, 2010.
52. Hu FB, Manson JE, Stampfer MJ, et al.: Diet, lifestyle, and the risk of type 2 diabetes mellitus in women. N Engl J Med 345: 790-797, 2001.
53. Koppes LL, Dekker JM, Hendriks HF, Bouter LM and Heine RJ: Moderate alcohol consumption lowers the risk of type 2 diabetes: a meta-analysis of prospective observational studies. Diabetes Care 28: 719-725, 2005. (Pubitemid 40315340)
54. Koppes LL, Dekker JM, Hendriks HF, Bouter LM and Heine RJ: Meta-analysis of the relationship between alcohol consumption and coronary heart disease and mortality in type 2 diabetic patients. Diabetologia 49: 648-652, 2006. (Pubitemid 43357536)
55. Mallon L, Broman JE and Hetta J: High incidence of diabetes in men with sleep complaints or short sleep duration: a 12-year follow-up study of a middle-aged population. Diabetes Care 28: 2762-2767, 2005. (Pubitemid 43951172)
56. Robertson R and Powers A (eds): Type 2 Diabetes, Update. The Endocrine Society, Chevy Chase, 2011.
57. Sun Q, Spiegelman D, van Dam RM, et al.: White rice, brown rice, and risk of type 2 diabetes in US men and women. Arch Intern Med 170: 961-969, 2010.
58. van Dam RM and Hu FB: Coffee consumption and risk of type 2 diabetes: a systematic review. JAMA 294: 97-104, 2005.
59. van Dam RM, Willett WC, Manson JE and Hu FB: Coffee, caffeine, and risk of type 2 diabetes: a prospective cohort study in younger and middle-aged US women. Diabetes Care 29: 398-403, 2006. (Pubitemid 44106525)
60. Cornelis MC, Monda KL, Yu K, et al.: Genome-wide metaanalysis identifies regions on 7p21 (AHR) and 15q24 (CYP1A2) as determinants of habitual caffeine consumption. PLoS Genet 7: e1002033, 2011.
61. Lane J: Caffeine, glucose metabolism, and type 2 diabetes. J Caffeine Res 1: 23-28, 2011.
62. Ho CH and Jap TS: Relationship of plasminogen activator inhibitor-1 with plasma insulin, glucose, triglyceride and cholesterol in Chinese patients with diabetes. Thromb Res 69: 271-277, 1993. (Pubitemid 23080703)
63. Festa A, Williams K, Tracy RP, Wagenknecht LE and Haffner SM: Progression of plasminogen activator inhibitor-1 and fibrinogen levels in relation to incident type 2 diabetes. Circulation 113: 1753-1759, 2006. (Pubitemid 43958468)
64. Jag UR, Zavadil J and Stanley FM: Insulin acts through FOXO3a to activate transcription of plasminogen activator inhibitor type 1. Mol Endocrinol 23: 1587-1602, 2009.
65. Zhao R, Ma X and Shen GX: Transcriptional regulation of plasminogen activator inhibitor-1 in vascular endothelial cells induced by oxidized very low density lipoproteins. Mol Cell Biochem 317: 197-204, 2008.
66. Collins SJ, Alexander SL, Lopez-Guisa JM, et al.: Plasminogen activator inhibitor-1 deficiency has renal benefits but some adverse systemic consequences in diabetic mice. Nephron Exp Nephrol 104: e23-e34, 2006.
67. Meigs JB, Dupuis J, Liu C, et al.: PAI-1 Gene 4G/5G polymorphism and risk of type 2 diabetes in a population-based sample. Obesity (Silver Spring) 14: 753-758, 2006. (Pubitemid 46219713)
68. Nagi DK, Tracy R and Pratley R: Relationship of hepatic and peripheral insulin resistance with plasminogen activator inhibitor-1 in Pima Indians. Metabolism 45: 1243-1247, 1996. (Pubitemid 26337670)
69. Park J, Seo JY and Ha H: Plasminogen activator inhibitor-1 antisense oligodeoxynucleotides abrogate mesangial fibronectin accumulation. Korean J Physiol Pharmacol 14: 385-390, 2010.
70. Lee HB and Ha H: Plasminogen activator inhibitor-1 and diabetic nephropathy. Nephrology (Carlton) 10 (Suppl): S11-S13, 2005. (Pubitemid 41743469)
71. Nicholas SB, Aguiniga E, Ren Y, et al.: Plasminogen activator inhibitor-1 deficiency retards diabetic nephropathy. Kidney Int 67: 1297-1307, 2005. (Pubitemid 40463106)
72. Seo JY, Park J, Yu MR, Kim YS, Ha H and Lee HB: Positive feedback loop between plasminogen activator inhibitor-1 and transforming growth factor-beta1 during renal fibrosis in diabetes. Am J Nephrol 30: 481-490, 2009.
73. Lassila M, Fukami K, Jandeleit-Dahm K, et al.: Plasminogen activator inhibitor-1 production is pathogenetic in experimental murine diabetic renal disease. Diabetologia 50: 1315-1326, 2007. (Pubitemid 46701559)
74. Miyata T and van Ypersele de Strihou C: Translation of basic science into clinical medicine: novel targets for diabetic nephropathy. Nephrol Dial Transplant 24: 1373-1377, 2009.
75. Huang Y, Border WA, Lawrence DA and Noble NA: Mechanisms underlying the antifibrotic properties of noninhibitory PAI-1 (PAI-1R) in experimental nephritis. Am J Physiol Renal Physiol 297: F1045-F1054, 2009.
76. Oh KS, Kim EY, Yoon M and Lee CM: Swim training improves leptin receptor deficiency-induced obesity and lipid disorder by activating uncoupling proteins. Exp Mol Med 39: 385-394, 2007. (Pubitemid 47037630)
77. Huang Y, Border WA, Yu L, Zhang J, Lawrence DA and Noble NA: A PAI-1 mutant, PAI-1R, slows progression of diabetic nephropathy. J Am Soc Nephrol 19: 329-338, 2008. (Pubitemid 351240654)
78. Madan R, Gupt B, Saluja S, Kansra UC, Tripathi BK and Guliani BP: Coagulation profile in diabetes and its association with diabetic microvascular complications. J Assoc Physicians India 58: 481-484, 2010.
79. Venugopal B, Sharon R, Abramovitz R, Khasin A and Miskin R: Plasminogen activator inhibitor-1 in cardiovascular cells: rapid induction after injecting mice with kainate or adrenergic agents. Cardiovasc Res 49: 476-483, 2001. (Pubitemid 32119565)
80. Keen H, Clark C and Laakso M: Reducing the burden of diabetes: managing cardiovascular disease. Diabetes Metab Res Rev 15: 186-196, 1999. (Pubitemid 29359036)
81. Sfredel V, Mota M, Traila A, Danoiu S and Matcas H: Disturbances of the coagulating equilibrium of blood in diabetes mellitus. Rom J Intern Med 37: 251-260, 1999. (Pubitemid 33315247)
82. Nagi DK, Knowler WC, Hanson RL, Ali VM and Yudkin JS: Plasminogen activator inhibitor (PAI-1) and non-insulin-dependent diabetes in Pima Indians, south Asians and Europeans. Populations at varying risk of NIDDM and coronary artery disease. Thromb Haemost 75: 921-927, 1996. (Pubitemid 26355348)
83. Juhan-Vague I, Alessi MC and Vague P: Thrombogenic and fibrinolytic factors and cardiovascular risk in non-insulin-dependent diabetes mellitus. Ann Med 28: 371-380, 1996. (Pubitemid 26268257)
84. Lopes C, Dina C, Durand E and Froguel P: PAI-1 polymorphisms modulate phenotypes associated with the metabolic syndrome in obese and diabetic Caucasian population. Diabetologia 46: 1284-1290, 2003. (Pubitemid 37214987)
85. Umpaichitra V, Hussain MM and Castells S: Plasminogen activator inhibitor-1 and tissue-plasminogen activator in minority adolescents with type 2 diabetes and obesity. Pediatr Res 58: 483-487, 2005. (Pubitemid 41254511)
86. Trost S, Pratley R and Sobel B: Impaired fibrinolysis and risk for cardiovascular disease in the metabolic syndrome and type 2 diabetes. Curr Diab Rep 6: 47-54, 2006.
87. Gorlatova NV, Cale JM, Elokdah H, et al.: Mechanism of inactivation of plasminogen activator inhibitor-1 by a small molecule inhibitor. J Biol Chem 282: 9288-9296, 2007. (Pubitemid 47093491)
88. Naessens D, Gils A, Compernolle G and Declerck PJ: Elucidation of a novel epitope of a substrate-inducing monoclonal antibody against the serpin PAI-1. J Thromb Haemost 1: 1028-1033, 2003.
89. Verhamme I, Kvassman JO, Day D, et al.: Accelerated conversion of human plasminogen activator inhibitor-1 to its latent form by antibody binding. J Biol Chem 274: 17511-17517, 1999.
90. Egelund R, Einholm AP, Pedersen KE, et al.: A regulatory hydrophobic area in the flexible joint region of plasminogen activator inhibitor-1, defined with fluorescent activity-neutralizing ligands. Ligand-induced serpin polymerization. J Biol Chem 276: 13077-13086, 2001.
91. Crandall DL, Hennan JK, Elokdah H, et al.: WAY-140312 reduces plasma PAI-1 while maintaining normal platelet aggregation. Biochem Biophys Res Commun 311: 904-908, 2003. (Pubitemid 37393403)
92. Elokdah H, Abou-Gharbia M, Hennan JK, et al.: Tiplaxtinin, a novel, orally efficacious inhibitor of plasminogen activator inhibitor-1: design, synthesis, and preclinical characterization. J Med Chem 47: 3491-3494, 2004. (Pubitemid 38822010)
93. Cale JM, Li SH, Warnock M, et al.: Characterization of a novel class of polyphenolic inhibitors of plasminogen activator inhibitor-1. J Biol Chem 285: 7892-7902, 2010.
94. Crandall DL, Elokdah H, Di L, Hennan JK, Gorlatova NV and Lawrence DA: Characterization and comparative evaluation of a structurally unique PAI-1 inhibitor exhibiting oral in-vivo efficacy. J Thromb Haemost 2: 1422-1428, 2004. (Pubitemid 40186141)
95. Izuhara Y, Takahashi S, Nangaku M, et al.: Inhibition of plasminogen activator inhibitor-1: its mechanism and effectiveness on coagulation and fibrosis. Arterioscler Thromb Vasc Biol 28: 672-677, 2008. (Pubitemid 351651332)
96. Rupin A, Gaertner R, Mennecier P, et al.: S35225 is a direct inhibitor of plasminogen activator inhibitor type-1 activity in the blood. Thromb Res 122: 265-270, 2008.
97. Podor TJ, Peterson CB, Lawrence DA, et al.: Type 1 plasminogen activator inhibitor binds to fibrin via vitronectin. J Biol Chem 275: 19788-19794, 2000. (Pubitemid 30441579)
98. Friederich PW, Levi M, Biemond BJ, et al.: Novel low-molecular- weight inhibitor of PAI-1 (XR5118) promotes endogenous fibrinolysis and reduces postthrombolysis thrombus growth in rabbits. Circulation 96: 916-921, 1997. (Pubitemid 27329628)
99. Gardell SJ, Krueger JA, Antrilli TA, et al.: Neutralization of plasminogen activator inhibitor I (PAI-1) by the synthetic antagonist PAI-749 via a dual mechanism of action. Mol Pharmacol 72: 897-906, 2007. (Pubitemid 47481413)
100. Lin Z, Jiang L, Yuan C, et al.: Structural basis for recognition of urokinase-type plasminogen activator by plasminogen activator inhibitor-1. J Biol Chem 286: 7027-7032, 2011.
101. Xue Y, Bjorquist P, Inghardt T, et al.: Interfering with the inhibitory mechanism of serpins: crystal structure of a complex formed between cleaved plasminogen activator inhibitor type 1 and a reactive-centre loop peptide. Structure 6: 627-636, 1998. (Pubitemid 28258115)
102. Alessi MC, Bastelica D, Morange P, et al.: Plasminogen activator inhibitor 1, transforming growth factor-beta1, and BMI are closely associated in human adipose tissue during morbid obesity. Diabetes 49: 1374-1380, 2000. (Pubitemid 30624239)
103. Brown NJ: Therapeutic potential of plasminogen activator inhibitor-1 inhibitors. Ther Adv Cardiovasc Dis 4: 315-324, 2010.
104. Grant PJ: Diabetes mellitus as a prothrombotic condition. J Intern Med 262: 157-172, 2007.