Alpha 2-antiplasmin (or α2-antiplasmin or plasmin inhibitor) is a serine protease inhibitor (serpin) responsible for inactivating plasmin. Plasmin is an important enzyme that participates in fibrinolysis and degradation of various other proteins. This protein is encoded by the SERPINF2 gene.[1]
Fibrinolysis (simplified). Blue arrows denote stimulation, and red arrows inhibition.
Very few cases (<20) of A2AP deficiency have been described. As plasmin degrades blood clots, impaired inhibition of plasmin leads to a bleeding tendency, which was severe in the cases reported.
In liver cirrhosis, there is decreased production of alpha 2-antiplasmin, leading to decreased inactivation of plasmin and an increase in fibrinolysis. This is associated with an increase risk of bleeding in liver disease.[2]
Interactions
Alpha 2-antiplasmin has been shown to interact with:
↑Sattar, Husain. Fundamentals of Pathology. Pathoma LLC, 2011, p. 36.
↑ 3.03.1Shieh BH, Travis J (May 1987). "The reactive site of human alpha 2-antiplasmin". The Journal of Biological Chemistry. 262 (13): 6055–9. PMID2437112.
↑Brower MS, Harpel PC (Aug 1982). "Proteolytic cleavage and inactivation of alpha 2-plasmin inhibitor and C1 inactivator by human polymorphonuclear leukocyte elastase". The Journal of Biological Chemistry. 257 (16): 9849–54. PMID6980881.
↑Wiman B, Collen D (Sep 1979). "On the mechanism of the reaction between human alpha 2-antiplasmin and plasmin". The Journal of Biological Chemistry. 254 (18): 9291–7. PMID158022.
Further reading
Martí-Fàbregas J, Borrell M, Cocho D, Martínez-Ramírez S, Martínez-Corral M, Fontcuberta J, Martí-Vilalta JL (Jan 2008). "Change in hemostatic markers after recombinant tissue-type plasminogen activator is not associated with the chance of recanalization". Stroke: A Journal of Cerebral Circulation. 39 (1): 234–6. doi:10.1161/STROKEAHA.107.493767. PMID18048863.
Nielsen VG (Oct 2007). "Hydroxyethyl starch enhances fibrinolysis in human plasma by diminishing alpha2-antiplasmin-plasmin interactions". Blood Coagulation & Fibrinolysis : An International Journal in Haemostasis and Thrombosis. 18 (7): 647–56. doi:10.1097/MBC.0b013e3282a167dc. PMID17890952.
Sazonova IY, Thomas BM, Gladysheva IP, Houng AK, Reed GL (Oct 2007). "Fibrinolysis is amplified by converting alpha-antiplasmin from a plasmin inhibitor to a substrate". Journal of Thrombosis and Haemostasis. 5 (10): 2087–94. doi:10.1111/j.1538-7836.2007.02652.x. PMID17883703.
Mutch NJ, Thomas L, Moore NR, Lisiak KM, Booth NA (Apr 2007). "TAFIa, PAI-1 and alpha-antiplasmin: complementary roles in regulating lysis of thrombi and plasma clots". Journal of Thrombosis and Haemostasis. 5 (4): 812–7. doi:10.1111/j.1538-7836.2007.02430.x. PMID17388801.
Hayashido Y, Hamana T, Ishida Y, Shintani T, Koizumi K, Okamoto T (Feb 2007). "Induction of alpha2-antiplasmin inhibits E-cadherin processing mediated by the plasminogen activator/plasmin system, leading to suppression of progression of oral squamous cell carcinoma via upregulation of cell-cell adhesion". Oncology Reports. 17 (2): 417–23. doi:10.3892/or.17.2.417. PMID17203182.
Lee KN, Jackson KW, Christiansen VJ, Chung KH, McKee PA (May 2004). "A novel plasma proteinase potentiates alpha2-antiplasmin inhibition of fibrin digestion". Blood. 103 (10): 3783–8. doi:10.1182/blood-2003-12-4240. PMID14751930.
Anderson NL, Polanski M, Pieper R, Gatlin T, Tirumalai RS, Conrads TP, Veenstra TD, Adkins JN, Pounds JG, Fagan R, Lobley A (Apr 2004). "The human plasma proteome: a nonredundant list developed by combination of four separate sources". Molecular & Cellular Proteomics. 3 (4): 311–26. doi:10.1074/mcp.M300127-MCP200. PMID14718574.
Kapadia C, Yousef GM, Mellati AA, Magklara A, Wasney GA, Diamandis EP (Jan 2004). "Complex formation between human kallikrein 13 and serum protease inhibitors". Clinica Chimica Acta; International Journal of Clinical Chemistry. 339 (1–2): 157–67. doi:10.1016/j.cccn.2003.10.009. PMID14687906.
Matsuno H, Okada K, Ueshima S, Matsuo O, Kozawa O (Aug 2003). "Alpha2-antiplasmin plays a significant role in acute pulmonary embolism". Journal of Thrombosis and Haemostasis. 1 (8): 1734–9. doi:10.1046/j.1538-7836.2003.00252.x. PMID12911586.
Magklara A, Mellati AA, Wasney GA, Little SP, Sotiropoulou G, Becker GW, Diamandis EP (Aug 2003). "Characterization of the enzymatic activity of human kallikrein 6: Autoactivation, substrate specificity, and regulation by inhibitors". Biochemical and Biophysical Research Communications. 307 (4): 948–55. doi:10.1016/S0006-291X(03)01271-3. PMID12878203.
Frank PS, Douglas JT, Locher M, Llinás M, Schaller J (Feb 2003). "Structural/functional characterization of the alpha 2-plasmin inhibitor C-terminal peptide". Biochemistry. 42 (4): 1078–85. doi:10.1021/bi026917n. PMID12549929.
Turner RB, Liu L, Sazonova IY, Reed GL (Sep 2002). "Structural elements that govern the substrate specificity of the clot-dissolving enzyme plasmin". The Journal of Biological Chemistry. 277 (36): 33068–74. doi:10.1074/jbc.M203782200. PMID12080056.
Askew YS, Pak SC, Luke CJ, Askew DJ, Cataltepe S, Mills DR, Kato H, Lehoczky J, Dewar K, Birren B, Silverman GA (Dec 2001). "SERPINB12 is a novel member of the human ov-serpin family that is widely expressed and inhibits trypsin-like serine proteinases". The Journal of Biological Chemistry. 276 (52): 49320–30. doi:10.1074/jbc.M108879200. PMID11604408.
Uszynski M, Klyszejko A, Zekanowska E (Dec 2000). "Plasminogen, alpha(2)-antiplasmin and complexes of plasmin-alpha(2)-antiplasmin (PAP) in amniotic fluid and blood plasma of parturient women". European Journal of Obstetrics, Gynecology, and Reproductive Biology. 93 (2): 167–71. doi:10.1016/S0301-2115(00)00283-9. PMID11074138.
