Skip to main content
SpringerLink
Log in

Influence of integrins on thrombus formation: a road leading to the unravelling of DVT

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Integrins are a group of transmembrane glycoprotein receptors that are responsible for platelet activation through bidirectional signalling. These receptors have left their footprints in various cellular events and have intrigued many groups of scientists that have led to some significant discoveries. A lot of the recent understanding of haemostasis has been possible due to the integrins filling the gaps in between several cellular mechanism. Apart from this, other important functions carried out by integrins are growth and maturation of cardiomyocytes, mechano-transduction, and interaction with actin cytoskeleton. The signalling cascade for integrin activation involves certain intracellular interacting proteins, which initiates the step-by-step activation procedure through ‘inside-out’ signalling. The signalling cascade gets activated through ‘outside-in’ signalling with the involvement of agonists such as ADP, Fibronectin, Vitronectin, and so on. This is a crucial step for the downstream processes of platelet spreading, followed by aggregation, clot progression and finally thrombus formation. Researchers throughout the world have shown direct relation of integrins with CVD and cardiac remodelling. The present review aims to summarize the information available so far on the involvement of integrins in thrombosis and its relationship to DVT. This information could be a bedrock of hidden answers to several questions on pathogenesis of deep vein thrombosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

ADP:

Adenosine diphosphate

ATP:

Adenosine triphosphate

bFGF:

basic fibroblast growth factor

CRP:

Collagen-related peptide

CVD:

Cardiovascular disease

EC:

Endothelial cell

ECM:

Extracellular matrix

EGF:

Epidermal growth factor

ESPRIT:

Enhanced suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy

FDA:

Food and Drug Administration

FERM:

protein 4.1, ezrin, radixin, moesin

FERMT:

Fermitin family member

FN:

Fibronectin

GI:

Gastrointestinal

GPCR:

G-Protein coupled receptor

GPVI:

Glycoprotein VI

IgG:

Immunoglobulin

ILK:

Integrin linked kinase

LV:

Left ventricle

MIG2:

Multicopy inhibitor of GAL gene 2

NPXY:

Asn-Pro-x-Tyr

OPN:

Osteopontin

oxLDL:

Oxidized low-density lipoprotein

PHSRN:

Pro-His-Ser-Arg-Asn

PLCβ:

Phospholipase C beta

PTB:

Phosphotyrosine binding domain

RGD:

Arginine-glycine-Aspartic acid

ST:

Sinus Tachycardia

THD:

Terminal head domain

tPA:

tissue Plasminogen Activator

TxA2:

Thromboxane A2

URP:

Urotensin-II-related peptide

VASP:

Vasodilator-stimulator phosphoprotein

VCAM-1:

Vascular cell adhesion molecule-1

VN:

Vitronectin

WT:

Wild type

References

  1. Ruoslahti E (1991) Integrins. J Clin Invest 87(1):1–5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Piotrowicz RS, Orchekowski RP, Nugent DJ, Yamada KY, Kunicki TJ (1988) Glycoprotein Ic-IIa functions as an activation-independent fibronectin receptor on human platelets. J Cell Biol 106(4):1359–1364

    Article  CAS  PubMed  Google Scholar 

  3. Tamkun JW, DeSimone DW, Fonda D, Patel RS, Buck C, Horwitz AF, Hynes RO (1986) Structure of integrin, a glycoprotein involved in the transmembrane linkage between fibronectin and actin. Cell 46(2):271–282

    Article  CAS  PubMed  Google Scholar 

  4. Holbro T, Hynes NE (2004) ErbB receptors: directing key signaling networks throughout life. Annu Rev Pharmacol Toxicol 44:195–217

    Article  CAS  PubMed  Google Scholar 

  5. Larson RS, Springer TA (1990) Structure and function of leukocyte integrins. Immunol Rev 114:181–217

    Article  CAS  PubMed  Google Scholar 

  6. Lu C, Oxvig C, Springer TA (1998) The structure of the β-propeller domain and C-terminal region of the integrin αM subunit dependence on β subunit association and prediction of domains. J Biol Chem 273(24):15138–15147

    Article  CAS  PubMed  Google Scholar 

  7. Campbell ID, Humphries MJ (2011) Integrin structure, activation, and interactions. Cold Spring Harb Perspect Biol 3(3):a004994

    Article  PubMed  PubMed Central  Google Scholar 

  8. Gullberg D, Gehlsen KR, Turner DC, Ahlen K, Zijenah LS, Barnes MJ, Rubin K (1992) Analysis of alpha 1 beta 1, alpha 2 beta 1 and alpha 3 beta 1 integrins in cell – collagen interactions: identification of conformation dependent alpha 1 beta 1 binding sites in collagen type I. EMBO J 11(11):3865–3873

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Gullberg D, Turner DC, Borg TK, Terracio L, Rubin K (1990) Different β1-integrin collagen receptors on rat hepatocytes and cardiac fibroblasts. Exp Cell Res 190(2):254–264

    Article  CAS  PubMed  Google Scholar 

  10. Schiro JA, Chan BM, Roswit WT, Kassner PD, Pentland AP, Hemler ME et al (1991) Integrin α2β1 (VLA-2) mediates reorganization and contraction of collagen matrices by human cells. Cell 67(2):403–410

    Article  CAS  PubMed  Google Scholar 

  11. Tiger CF, Fougerousse F, Grundström G, Velling T, Gullberg D (2001) α11β1 integrin is a receptor for interstitial collagens involved in cell migration and collagen reorganization on mesenchymal nonmuscle cells. Dev Biol 237(1):116–129

    Article  CAS  PubMed  Google Scholar 

  12. Ginsberg MH, Partridge A, Shattil SJ (2005) Integrin regulation. Curr Opin Cell Biol 5:509–516

    Article  Google Scholar 

  13. Hynes RO (2002) Integrins: bidirectional, allosteric signaling machines. Cell 110(6):673–687

    Article  CAS  PubMed  Google Scholar 

  14. Calderwood DA, Yan B, de Pereda JM, Alvarez BG, Fujioka Y, Liddington RC, Ginsberg MH (2002) The phosphotyrosine binding-like domain of talin activates integrins. J BiolChem 277(24):21749–21758

    CAS  Google Scholar 

  15. Bouaouina M, Lad Y, Calderwood DA (2008) The N-terminal domains of talin cooperate with the phosphotyrosine binding-like domain to activate β1 and β3 integrins. J Biol Chem 283(10):6118–6125

    Article  CAS  PubMed  Google Scholar 

  16. Nieswandt B, Varga-Szabo D, Elvers M (2009) Integrins in platelet activation. J Thromb Haemost Suppl 1:206–209

    Article  Google Scholar 

  17. Calderwood DA (2004) Integrin activation. J Cell Sci 117:657–666

    Article  CAS  PubMed  Google Scholar 

  18. Nieswandt B, Moser M, Pleines I, Varga-Szabo D, Monkley S, Critchley D, Fässler R (2007) Loss of talin1 in platelets abrogates integrin activation, platelet aggregation, and thrombus formation in vitro and in vivo. J Exp Med 204(13):3113–3118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Petrich BG, Fogelstrand P, Partridge AW, Yousefi N, Ablooglu AJ, Shattil SJ, Ginsberg MH (2007) The antithrombotic potential of selective blockade of talin-dependent integrin α IIb β 3 (platelet GPIIb–IIIa) activation. J Clin Invest 117(8):2250–2259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hodivala-Dilke KM, McHugh KP, Tsakiris DA, Rayburn H, Crowley D, Ullman-Culleré M et al (1999) β3-integrin–deficient mice are a model for Glanzmann thrombasthenia showing placental defects and reduced survival. J Clin Invest 103(2):229–238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Larjava H, Plow EF, Wu C (2008) Kindlins: essential regulators of integrin signalling and cell–matrix adhesion. EMBO Rep 9(12):1203–1208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Shattil SJ, Kim C, Ginsberg MH (2010) The final steps of integrin activation: the end game. Nat Rev Mol Cell Biol 11(4):288–300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Legate KR, Wickström SA, Fässler R (2009) Genetic and cell biological analysis of integrin outside-in signaling. Genes Dev 23:397–418

    Article  CAS  PubMed  Google Scholar 

  24. Mackinnon AC, Qadota H, Norman KR, Moerman DG, Williams BD (2002) C. elegans PAT-4/ILK functions as an adaptor protein within integrin adhesion complexes. Curr Biol 12(10):787–797

    Article  CAS  PubMed  Google Scholar 

  25. Tao L, Zhang Y, Xi X, Kieffer N (2010) Recent advances in the understanding of the molecular mechanisms regulating platelet integrin αIIbβ3 activation. Protein Cell 1(7):627–637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Montanez E, Ussar S, Schifferer M, Bösl M, Zent R, Moser M, Fässler R (2008) Kindlin-2 controls bidirectional signaling of integrins. Genes Dev 22:1325–1330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kloeker S, Major MB, Calderwood DA, Ginsberg MH, Jones DA, Beckerle MC (2004) The Kindler syndrome protein is regulated by transforming growth factor-β and involved in integrin-mediated adhesion. J Biol Chem 279(8):6824–6833

    Article  CAS  PubMed  Google Scholar 

  28. Tu Y, Wu S, Shi X, Chen K, Wu C (2003) Migfilin and Mig-2 link focal adhesions to filamin and the actin cytoskeleton and function in cell shape modulation. Cell 113(1):37–47

    Article  CAS  PubMed  Google Scholar 

  29. Moser M, Nieswandt B, Ussar S, Pozgajova M, Fässler R (2008) Kindlin-3 is essential for integrin activation and platelet aggregation. Nat Med 3:325–330

    Article  Google Scholar 

  30. Moser M, Legate KR, Zent R, Fässler R (2009) The tail of integrins, talin, and kindlins. Science 324(5929):895–899

    Article  CAS  PubMed  Google Scholar 

  31. Li Z, Zhang G, Feil R, Han J, Du X (2006) Sequential activation of p38 and ERK pathways by cGMP-dependent protein kinase leading to activation of the platelet integrin αIIbβ3. Blood 107(3):965–972

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Robbins SM, Suttorp VV, Weeks G, Spiegelman GB (1990) A ras-related gene from the lower eukaryote Dictyostelium that is highly conserved relative to the human rap genes. Nucleic Acids Res 18(17):5265–5269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Hariharan IK, Carthew RW, Rubin GM (1991) The Drosophila roughened mutation: activation of a rap homolog disrupts eye development and interferes with cell determination. Cell 67(4):717–722

    Article  CAS  PubMed  Google Scholar 

  34. Robbins SM, Khosla M, Thiery R, Weeks G, Spiegelman GB (1991) Ras-related genes in Dictyosteliumdiscoideum. Dev Genet 12(1-2):147–153

    Article  CAS  PubMed  Google Scholar 

  35. Díez J, Querejeta R, López B, González A, Larman M, Martínez Ubago JL (2002) Losartan-dependent regression of myocardial fibrosis is associated with reduction of left ventricular chamber stiffness in hypertensive patients. Circulation 105(21):2512–2517

    Article  PubMed  Google Scholar 

  36. Brilla CG, Maisch B, Weber KT (1992) Myocardial collagen matrix remodelling in arterial hypertension. Eur Heart J 13(suppl_D):24–32

    Article  CAS  PubMed  Google Scholar 

  37. Camelliti P, Borg TK, Kohl P (2005) Structural and functional characterisation of cardiac fibroblasts. Cardiovasc Res 65(1):40–51

    Article  CAS  PubMed  Google Scholar 

  38. Chrzanowska-Wodnicka M, Smyth SS, Schoenwaelder SM, Fischer TH, White GC (2005) Rap1b is required for normal platelet function and hemostasis in mice. J Clin Invest 115(3):680–687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Ieda M, Tsuchihashi T, Ivey KN, Ross RS, Hong TT, Shaw RM, Srivastava D (2009) Cardiac fibroblasts regulate myocardial proliferation through β1 integrin signaling. Dev Cell 16(2):233–244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Lopez-Sanchez C, Climent V, Schoenwolf GC, Alvarez IS, Garcia-Martinez V (2002) Induction of cardiogenesis by Hensen’s node and fibroblast growth factors. Cell Tissue Res 309:237–249

    Article  CAS  PubMed  Google Scholar 

  41. Kamkin A, Kiseleva I, Lozinsky I, Scholz H (2005) Electrical interaction of mechanosensitive fibroblasts and myocytes in the heart. Basic Res Cardiol 100:337–345

    Article  CAS  PubMed  Google Scholar 

  42. Aneja A, Tang WW, Bansilal S, Garcia MJ, Farkouh ME (2008) Diabetic cardiomyopathy: insights into pathogenesis, diagnostic challenges, and therapeutic options. Am J Med 121(9):748–757

    Article  PubMed  Google Scholar 

  43. Hinz B (2015) The extracellular matrix and transforming growth factor-β1: tale of a strained relationship. Matrix Biol 47:54–65

    Article  CAS  PubMed  Google Scholar 

  44. Nicoletti A, Michel JB (1999) Cardiac fibrosis and inflammation: interaction with hemodynamic and hormonal factors. Cardiovasc Res 41(3):532–543

    Article  CAS  PubMed  Google Scholar 

  45. Barczyk MM, Lu N, Popova SN, Bolstad AI, Gullberg D (2013) α11β1 integrin-mediated MMP-13-dependent collagen lattice contraction by fibroblasts: evidence for integrin-coordinated collagen proteolysis. J Cell Physiol 228(5):1108–1119

    Article  CAS  PubMed  Google Scholar 

  46. Carracedo S, Lu N, Popova SN, Jonsson R, Eckes B, Gullberg D (2010) The fibroblast integrin α11β1 is induced in a mechanosensitive manner involving activin A and regulates myofibroblast differentiation. J Biol Chem 285(14):10434–10445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Civitarese RA, Talior-Volodarsky I, Desjardins JF, Kabir G, Switzer J, Mitchell M et al (2016) The α11 integrin mediates fibroblast–extracellular matrix–cardiomyocyte interactions in health and disease. Am J Physiol Heart Circ Physiol 311(1):H96–H106

    Article  PubMed  Google Scholar 

  48. Kai H, Muraishi A, Sugiu Y, Nishi H, Seki Y, Kuwahara F et al (1998) Expression of proto-oncogenes and gene mutation of sarcomeric proteins in patients with hypertrophic cardiomyopathy. Circ Res 83(6):594–601

    Article  CAS  PubMed  Google Scholar 

  49. Samarel AM (2005) Costameres, focal adhesions, and cardiomyocyte mechanotransduction. Am J Physiol Heart Circ Physiol 289(6):H2291–H2301

    Article  CAS  PubMed  Google Scholar 

  50. Maitra N, Flink IL, Bahl JJ, Morkin E (2000) Expression of α and β integrins during terminal differentiation of cardiomyocytes. Cardiovasc Res 47(4):715–725

    Article  CAS  PubMed  Google Scholar 

  51. Bouzeghrane F, Mercure C, Reudelhuber TL, Thibault G (2004) α8β1 integrin is upregulated in myofibroblasts of fibrotic and scarring myocardium. J Mol Cell Cardiol 3:343–353

    Article  Google Scholar 

  52. Arora PD, Narani N, McCulloch CA (1999) The compliance of collagen gels regulates transforming growth factor-β induction of α-smooth muscle actin in fibroblasts. Am J Pathol 154(3):871–882

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Topol E, Califf R, Weisman H, Ellis S, Tcheng J, Worley S et al (1994) Randomised trial of coronary intervention with antibody against platelet IIb/IIIa integrin for reduction of clinical restenosis: results at six months. Lancet 343(8902):881–886

    Article  CAS  PubMed  Google Scholar 

  54. Coller BS (1997) Platelet GPIIb/IIIa antagonists: the first anti-integrin receptor therapeutics. J Clin Invest 99(7):1467–1471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Thannickal VJ, Lee DY, White ES, Cui Z, Larios JM, Chacon R et al (2003) Myofibroblast differentiation by transforming growth factor-β1 is dependent on cell adhesion and integrin signaling via focal adhesion kinase. J Biol Chem 278(14):12384–12389

    Article  CAS  PubMed  Google Scholar 

  56. Kleiman NS, Raizner AE, Jordan R, Wang AL, Norton D, Mace KF et al (1995) Differential inhibition of platelet aggregation induced by adenosine diphosphate or a thrombin receptor-activating peptide in patients treated with bolus chimeric 7E3 Fab: implications for inhibition of the internal pool of GPIIb/IIIa receptors. J Am Coll Cardiol 26(7):1665–1671

    Article  CAS  PubMed  Google Scholar 

  57. Kereiakes DJ (2003) Inflammation as a therapeutic target: a unique role for abciximab. Am Heart J 146(4):S1–S4

    Article  CAS  PubMed  Google Scholar 

  58. Blindt R, Bosserhoff AK, Krott N, Vogt F, Hanrath P, Demircan L, vom Dahl J (2002) Decrease of vascular smooth muscle cell locomotion by abciximab, but not tirofiban: a possible role of different affinity to alpha v beta 3 integrins. Coron Artery Dis 13(7):357–364

    Article  PubMed  Google Scholar 

  59. O’Shea JC, Hafley GE, Greenberg S, Hasselblad V, Lorenz TJ, Kitt MM et al (2001) Platelet glycoprotein IIb/IIIa integrin blockade with eptifibatide in coronary stent intervention: the ESPRIT trial: a randomized controlled trial. JAMA 285(19):2468–2473

    Article  PubMed  Google Scholar 

  60. Leclerc JR (2002) Platelet glycoprotein IIb/IIIa antagonists: lessons learned from clinical trials and future directions. Crit Care Med 30(5 Suppl):S332–S340

    Article  CAS  PubMed  Google Scholar 

  61. Jennings LK (2005) Current strategies with eptifibatide and other antiplatelet agents in percutaneous coronary intervention and acute coronary syndromes. Expert Opin Drug Metab Toxicol 1(4):727–737

    Article  CAS  PubMed  Google Scholar 

  62. Brener SJ, Barr LA, Burchenal JEB, Katz S, George BS, Jones AA et al (1998) Randomized, placebo-controlled trial of platelet glycoprotein IIb/IIIa blockade with primary angioplasty for acute myocardial infarction. Circulation 98(8):734–741

    Article  CAS  PubMed  Google Scholar 

  63. Grines CL, Cox DA, Stone GW, Garcia E, Mattos LA, Giambartolomei A et al (1999) Coronary angioplasty with or without stent implantation for acute myocardial infarction. N Engl J Med 341:1949–1956

    Article  CAS  PubMed  Google Scholar 

  64. Smith SC Jr (2006) American College of Cardiology/American Heart Association Task Force on Practice Guidelines; American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions Writing Committee to update the 2001 guidelines for percutaneous coronary intervention. ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention-summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI). Circulation 113(1):156–175

    PubMed  Google Scholar 

  65. Yoganathan TN, Costello P, Chen X, Jabali M, Yan J, Leung D et al (2000) Integrin-linked kinase (ILK): a “hot” therapeutic target. Biochem Pharmacol 60(8):1115–1119

    Article  CAS  PubMed  Google Scholar 

  66. Zhang X, Hu K, Li CY (2001) Protection against oxidized low-density lipoprotein–induced vascular endothelial cell death by integrin-linked kinase. Circulation 104(23):2762–2766

    Article  CAS  PubMed  Google Scholar 

  67. Fang CC, Chou TH, Huang JW, Lee CC, Chen SC (2018) The small molecule inhibitor QLT-0267 decreases the production of fibrin-induced inflammatory cytokines and prevents post-surgical peritoneal adhesions. Sci Rep 8:9481

    Article  PubMed  PubMed Central  Google Scholar 

  68. Zhang ZC, Li SJ, Yang YZ, Chen RZ, Ge JB, Chen HZ (2004) Microarray analysis of extracellular matrix genes expression in myocardium of mouse with Coxsackie virus B3 myocarditis. Chin Med J 117(8):1228–1231

    CAS  PubMed  Google Scholar 

  69. Uehata M, Ishizaki T, Satoh H, Ono T, Kawahara T, Morishita T, Tamakawa H, Yamagami K, Inui J, Maekawa M, Narumiya S (1997) Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature 389(6654):990–994

    Article  CAS  PubMed  Google Scholar 

  70. Hattori T, Shimokawa H, Higashi M, Hiroki J, Mukai Y, Tsutsui H et al (2004) Long-term inhibition of Rho-kinase suppresses left ventricular remodeling after myocardial infarction in mice. Circulation 109(18):2234–2239

    Article  CAS  PubMed  Google Scholar 

  71. Qvigstad E, Sjaastad I, Brattelid T, Nunn C, Swift F, Birkeland JAK et al (2005) Dual serotonergic regulation of ventricular contractile force through 5-HT2A and 5-HT4 receptors induced in the acute failing heart. Circ Res 97:268–276

    Article  CAS  PubMed  Google Scholar 

  72. Ishizaki T, Uehata M, Tamechika I, Keel J, Nonomura K, Maekawa M, Narumiya S (2000) Pharmacological properties of Y-27632, a specific inhibitor of rho-associated kinases. Mol Pharmacol 57(5):976–983

    CAS  PubMed  Google Scholar 

  73. Inokuchi K, Ito A, Fukumoto Y, Matoba T, Shiose A, Nishida T et al (2004) Usefulness of fasudil, a Rho-kinase inhibitor, to treat intractable severe coronary spasm after coronary artery bypass surgery. J Cardiovasc Pharmacol 44(3):275–277

    Article  CAS  PubMed  Google Scholar 

  74. Guijarro C, Blanco-Colio LM, Ortego M, Alonso C, Ortiz A, Plaza JJ et al (1998) 3-Hydroxy-3-methylglutaryl coenzyme a reductase and isoprenylation inhibitors induce apoptosis of vascular smooth muscle cells in culture. Circ Res 83(5):490–500

    Article  CAS  PubMed  Google Scholar 

  75. Kern A, Eble J, Golbik R, Kühn K (1993) Interaction of type IV collagen with the isolated integrins α1β1 and α2β1.Eur. J Biochem 215(1):151–159

    CAS  Google Scholar 

  76. Kamata T, Takada Y (1994) Direct binding of collagen to the I domain of integrin alpha 2 beta 1 (VLA-2, CD49b/CD29) in a divalent cation-independent manner. J Biol Chem 269(42):26006–26010

    Article  CAS  PubMed  Google Scholar 

  77. Nykvist P, Tu H, Ivaska J, Käpylä J, Pihlajaniemi T, Heino J (2000) Distinct recognition of collagen subtypes by α1β1 and α2β1 integrins α1β1 mediates cell adhesion to type Xiii collagen. J Biol Chem 275(11):8255–8261

    Article  CAS  PubMed  Google Scholar 

  78. Pfaff M, Göhring W, Brown JC, Timpl R (1994) Binding of purified collagen receptors (α1β1, α2β1) and RGD-dependent integrins to laminins and laminin fragments. Eur J Biochem 225(3):975–984

    Article  CAS  PubMed  Google Scholar 

  79. Decline F, Rousselle P (2001) Keratinocyte migration requires alpha2beta1 integrin-mediated interaction with the laminin 5 gamma2 chain. J Cell Sci 114(Pt 4):811–823

    Article  CAS  PubMed  Google Scholar 

  80. Zotz RB, Winkelmann BR, Müller C, Boehm BO, März W, Scharf RE (2005) Association of polymorphisms of platelet membrane integrins αIIbβ3 (HPA-1b/PlA2) and α2β1 (α2807TT) with premature myocardial infarction. J Thromb Haemost 3(7):1522–1529

    Article  CAS  PubMed  Google Scholar 

  81. Funahashi Y, Sugi NH, Semba T, Yamamoto Y, Hamaoka S, Tsukahara-Tamai N et al (2002) Sulfonamide derivative, E7820, is a unique angiogenesis inhibitor suppressing an expression of integrin α2 subunit on endothelium. Cancer Res 62(21):6116–6123

    CAS  PubMed  Google Scholar 

  82. Semba T, Funahashi Y, Ono N, Yamamoto Y, Sugi NH, Asada M et al (2004) An angiogenesis inhibitor E7820 shows broad-spectrum tumor growth inhibition in a xenograft model: possible value of integrin α2 on platelets as a biological marker. Clin Cancer Res 10(4):1430–1438

    Article  CAS  PubMed  Google Scholar 

  83. Springer TA (1994) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76(2):301–314

    Article  CAS  PubMed  Google Scholar 

  84. Noseworthy JH, Kirkpatrick P (2005) Natalizumab. Nat Rev Drug Discov 4(2):101–102

    Article  CAS  PubMed  Google Scholar 

  85. Léger OJ, Yednock TA, Tanner L, Horner HC, Hines DK, Keen S et al (1997) Humanization of a mouse antibody against human alpha-4 integrin: a potential therapeutic for the treatment of multiple sclerosis. Hum Antibodies 8(1):3–16

    Article  PubMed  Google Scholar 

  86. Stoeltzing O, Liu W, Reinmuth N, Fan F, Parry GC, Parikh AA et al (2003) Inhibition of integrin α5β1 function with a small peptide (ATN-161) plus continuous 5-FU infusion reduces colorectal liver metastases and improves survival in mice. Int J Cancer 104(4):496–503

    Article  CAS  PubMed  Google Scholar 

  87. Cheresh DA (1987) Human endothelial cells synthesize and express an Arg-Gly-Asp-directed adhesion receptor involved in attachment to fibrinogen and von Willebrand factor. Proc Natl Acad Sci U S A 84(18):6471–6475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Stromblad S, Becker JC, Yebra M, Brooks PC, Cheresh DA (1996) Suppression of p53 activity and p21WAF1'C'P1 expression by vascular cell integrin a& during angiogenesis. J Clin Invest 98(2):426–433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Brooks PC, Montgomery AM, Rosenfeld M, Reisfeld RA, Hu T, Klier G, Cheresh DA (1994) Integrin αvβ3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell 79(7):1157–1164

    Article  CAS  PubMed  Google Scholar 

  90. Pc B, Clark RA, Cheresh DA (1994) Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science. 264(5158):569–571

    Article  Google Scholar 

  91. Brooks PC, Strömblad S, Klemke R, Visscher D, Sarkar FH, Cheresh DA (1995) Antiintegrin alpha v beta 3 blocks human breast cancer growth and angiogenesis in human skin. J Clin Invest 96(4):1815–1822

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Marcinkiewicz C, Rosenthal LA, Mosser DM, Kunicki TJ, Niewiarowski S (1996) Immunological characterization of eristostatin and echistatin binding sites on αIIb β3 and αVβ3 integrins. Biochem J 317(Pt 3):817–825

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Guidance on the use of glycoprotein IIb/IIIa inhibitors in the treatment of acute coronary syndromes. National Institute for Clinical Excellence, 2000. https://www.nice.org.uk/guidance/ta47/resources/guidance-on-the-use-of-glycoprotein-iibiiia-inhibitors-in-the-treatment-of-acute-coronary-syndromes-pdf-2294582158789

  94. Marso SP, Lincoff AM, Ellis SG, Bhatt DL, Tanguay JF, Kleiman NS et al (1999) Optimizing the percutaneous interventional outcomes for patients with diabetes mellitus: results of the EPISTENT (Evaluation of platelet IIb/IIIa inhibitor for stenting trial) diabetic substudy. Circulation. 100:2477–2484

    Article  CAS  PubMed  Google Scholar 

  95. Kastrati A, Mehilli J, Dirschinger J, Schricke U, Neverve J, Pache J et al (2002) Myocardial salvage after coronary stenting plus abciximab versus fibrinolysis plus abciximab in patients with acute myocardial infarction: a randomised trial. Lancet. 359(9310):920–925

    Article  CAS  PubMed  Google Scholar 

  96. Admiral Investigators (2005) Three-year duration of benefit from abciximab in patients receiving stents for acute myocardial infarction in the randomized double-blind ADMIRAL study. Eur Heart J 26(23):2520–2523

    Article  Google Scholar 

  97. Lynch DK, Ellis CA, Edwards PA, Hiles ID (1999) Integrin-linked kinase regulates phosphorylation of serine 473 of protein kinase B by an indirect mechanism. Oncogene. 18(56):8024–8032

    Article  CAS  PubMed  Google Scholar 

  98. Nemerow GR, Stewart PL (1999) Role of αv integrins in adenovirus cell entry and gene delivery. Microbiol Mol Biol Rev 63(3):725–734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Vootukuri S et al (2019) Preclinical studies of RUC-4, a novel platelet αIIbβ3 antagonist, in non-human primates and with human platelets. J Clin Transl Sci 3(2-3):65–74

    Article  PubMed  PubMed Central  Google Scholar 

  100. Bentur OS, Coller BS (2019) In vitro effects of the novel platelet αIIbβ3 receptor antagonist RUC-4 on the verifynow assays: potential for point-of-care monitoring of RUC-4 therapy. Blood 134(Supplement_1):166

    Article  Google Scholar 

  101. Simons P et al (2018) Small-volume flow cytometry-based multiplex analysis of the activity of small GTPases. Rho GTPases. Methods Mol Biol 1821:177–195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Defence Institute of Physiology and Allied Sciences (DIPAS), Defence Research and Development Organization (DRDO), Lucknow Road, Timarpur, Delhi, 110054, India

    Nilanjana Ghosh, Iti Garg, Swati Srivastava & Bhuvnesh Kumar

Authors
  1. Nilanjana Ghosh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Iti Garg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Swati Srivastava
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bhuvnesh Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Ms NG involved in literature survey and writing. Dr IG participated in conceptualization, wiring, and editing. Dr SS involved inpreparation of figures and proof reading. Dr BK did editing and proof reading.

Corresponding author

Correspondence to Iti Garg.

Ethics declarations

Conflict of interest

The authors have declared that no competing interests exist.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ghosh, N., Garg, I., Srivastava, S. et al. Influence of integrins on thrombus formation: a road leading to the unravelling of DVT. Mol Cell Biochem 476, 1489–1504 (2021). https://doi.org/10.1007/s11010-020-03961-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-020-03961-x

Keywords

Search

Navigation