alpha macroglobulins


Summary: Glycoproteins with a molecular weight of approximately 620,000 to 680,000. Precipitation by electrophoresis is in the alpha region. They include alpha 1-macroglobulins and alpha 2-macroglobulins. These proteins exhibit trypsin-, chymotrypsin-, thrombin-, and plasmin-binding activity and function as hormonal transporters.

Top Publications

  1. Myers R, Benhamou Y, Imbert Bismut F, Thibault V, Bochet M, Charlotte F, et al. Serum biochemical markers accurately predict liver fibrosis in HIV and hepatitis C virus co-infected patients. AIDS. 2003;17:721-5 pubmed
    ..An index including five biochemical markers accurately predicts significant fibrosis in patients with HIV/HCV co-infection, and may substantially reduce the necessity for liver biopsy. ..
  2. Myers R, Tainturier M, Ratziu V, Piton A, Thibault V, Imbert Bismut F, et al. Prediction of liver histological lesions with biochemical markers in patients with chronic hepatitis B. J Hepatol. 2003;39:222-30 pubmed
    ..80) may prevent liver biopsies in 46% of patients while maintaining 92% accuracy. The aminotransferases and an index including five biochemical markers are accurate noninvasive markers of HBV-related activity and fibrosis, respectively. ..
  3. Arandjelovic S, Dragojlovic N, Li X, Myers R, Campana W, Gonias S. A derivative of the plasma protease inhibitor alpha(2)-macroglobulin regulates the response to peripheral nerve injury. J Neurochem. 2007;103:694-705 pubmed
    ..These studies demonstrate that an alpha2M derivative is capable of regulating the response to peripheral nerve injury by a mechanism that requires low-density lipoprotein receptor-related protein-1. ..
  4. Widegren H, Korsgren M, Andersson M, Greiff L. Effects of TNFalpha on the human nasal mucosa in vivo. Respir Med. 2007;101:1982-7 pubmed
    ..Increased nasal mucosal output of TNFalpha has been demonstrated in allergic rhinitis, but the effect of TNFalpha on the human nasal mucosa has not been examined in vivo...
  5. Adler V, Davidowitz E, Tamburi P, Rojas P, Grossman A. Alpha2-macroglobulin is a potential facilitator of prion protein transformation. Amyloid. 2007;14:1-10 pubmed
    ..Purification of proteins from this fraction led to the identification of alpha2-macroglobulin as an active component suggesting that it may facilitate conformational changes in prion protein in spontaneous forms of prion disease. ..
  6. Hart J, Gunn M, Pizzo S. A CD91-positive subset of CD11c+ blood dendritic cells: characterization of the APC that functions to enhance adaptive immune responses against CD91-targeted antigens. J Immunol. 2004;172:70-8 pubmed
    ..Therefore, CD11c(+) lin(-) DC use CD91/LRP to facilitate the uptake and subsequent presentation of an array of Ags complexed within the CD91/LRP ligand, the activated form of alpha2-macroglobulin (alpha2M*). ..
  7. Beheiri A, Langer C, Düring C, Krümpel A, Thedieck S, Nowak Gottl U. Role of elevated alpha2-macroglobulin revisited: results of a case-control study in children with symptomatic thromboembolism. J Thromb Haemost. 2007;5:1179-84 pubmed
    ..9/1.9-18.3; DVT, 7.2/2.1-24.4). The procoagulant properties of elevated alpha2MG levels independently increase the odds of stroke and DVT in white children. ..
  8. Imbert Bismut F, Messous D, Thibault V, Thibaut V, Myers R, Piton A, et al. Intra-laboratory analytical variability of biochemical markers of fibrosis (Fibrotest) and activity (Actitest) and reference ranges in healthy blood donors. Clin Chem Lab Med. 2004;42:323-33 pubmed
    ..075+/-0.004 and 0.068+/-0.004, respectively. The low intra-laboratory and intra-patient variability in Fibrotest and Actitest results confirm Fibrotest and Actitest reliability. ..
  9. Adams L, Bulsara M, Rossi E, DeBoer B, Speers D, George J, et al. Hepascore: an accurate validated predictor of liver fibrosis in chronic hepatitis C infection. Clin Chem. 2005;51:1867-73 pubmed
    ..5 had 74% specificity and 88% sensitivity for advanced fibrosis. A model of 4 serum markers plus age and sex provides clinically useful information regarding different fibrosis stages among hepatitis C patients. ..

More Information


  1. Galliano M, Toulza E, Jonca N, Gonias S, Serre G, Guerrin M. Binding of alpha2ML1 to the low density lipoprotein receptor-related protein 1 (LRP1) reveals a new role for LRP1 in the human epidermis. PLoS ONE. 2008;3:e2729 pubmed publisher
    ..Our findings are consistent with endocytosis by LRP1 of complexes formed between alpha2ML1 and proteases. LRP1 may thus control desquamation by regulating the biodisponibility of extracellular proteases. ..
  2. Saunders A, Tanzi R. Welcome to the complex disease world. Alpha2-macroglobulin and Alzheimer's disease. Exp Neurol. 2003;184:50-3 pubmed
  3. Wong C, Mruk D, Siu M, Cheng C. Blood-testis barrier dynamics are regulated by {alpha}2-macroglobulin via the c-Jun N-terminal protein kinase pathway. Endocrinology. 2005;146:1893-908 pubmed
  4. Arandjelovic S, Hall B, Gonias S. Mutation of lysine 1370 in full-length human alpha2-macroglobulin blocks binding to the low density lipoprotein receptor-related protein-1. Arch Biochem Biophys. 2005;438:29-35 pubmed
    ..7 cells was blocked by receptor-associated protein, indicating an essential role for LRP-1. These studies demonstrate that a single mutation in full-length r(alpha)2M is sufficient to block binding to LRP-1. ..
  5. Tayade C, Esadeg S, Fang Y, Croy B. Functions of alpha 2 macroglobulins in pregnancy. Mol Cell Endocrinol. 2005;245:60-6 pubmed
    ..Here, we review the A2M gene families of mice and humans, the predicted structural relationships between A2M and its pregnancy induced forms and the postulated roles for this gene family in normal pregnancy. ..
  6. Galliano M, Toulza E, Gallinaro H, Jonca N, Ishida Yamamoto A, Serre G, et al. A novel protease inhibitor of the alpha2-macroglobulin family expressed in the human epidermis. J Biol Chem. 2006;281:5780-9 pubmed
    ..Therefore, alpha2ML1 is the first alpha2M family member detected in the epidermis. It may play an important role during desquamation by inhibiting extracellular proteases. ..
  7. Dolmer K, Gettins P. Three complement-like repeats compose the complete alpha2-macroglobulin binding site in the second ligand binding cluster of the low density lipoprotein receptor-related protein. J Biol Chem. 2006;281:34189-96 pubmed
  8. Zhang Y, Ge G, Greenspan D. Inhibition of bone morphogenetic protein 1 by native and altered forms of alpha2-macroglobulin. J Biol Chem. 2006;281:39096-104 pubmed
    ..These findings suggest possible therapeutic interventions involving ectopic expression of modified versions of alpha(2)-macroglobulin in the treatment of fibrotic conditions. ..
  9. Pineda Salgado L, Craig E, Blank R, Kessler D. Expression of Panza, an alpha2-macroglobulin, in a restricted dorsal domain of the primitive gut in Xenopus laevis. Gene Expr Patterns. 2005;6:3-10 pubmed
    ..The expression of Panza in endodermal cells adjacent to the notochord points to a potential role for Panza in signal modulation and/or morphogenesis of the primitive gut. ..
  10. Patel K, Gordon S, Jacobson I, Hezode C, Oh E, Smith K, et al. Evaluation of a panel of non-invasive serum markers to differentiate mild from moderate-to-advanced liver fibrosis in chronic hepatitis C patients. J Hepatol. 2004;41:935-42 pubmed
    ..Prospective studies are required to determine the potential utility of the marker panel in guiding treatment decisions and following disease progression. ..
  11. Anderson R, Cianciolo G, Kennedy M, Pizzo S. Alpha 2-macroglobulin binds CpG oligodeoxynucleotides and enhances their immunostimulatory properties by a receptor-dependent mechanism. J Leukoc Biol. 2008;83:381-92 pubmed
    ..CpG ODN bound to alpha 2M* are also protected from degradation by nucleases. This novel targeting technology may improve CpG ODN-based therapeutics by increasing efficacy at reduced doses, thus reducing side-effects and cost. ..
  12. Luan Y, Kong L, Howell D, Ilalov K, Fajardo M, Bai X, et al. Inhibition of ADAMTS-7 and ADAMTS-12 degradation of cartilage oligomeric matrix protein by alpha-2-macroglobulin. Osteoarthritis Cartilage. 2008;16:1413-20 pubmed publisher
    ..Furthermore, a(2)M is a novel substrate for ADAMTS-7 and ADAMTS-12. More significantly, a(2)M represents the first endogenous inhibitor of ADAMTS-7 and ADAMTS-12. ..
  13. Myers R, Ratziu V, Imbert Bismut F, Charlotte F, Poynard T. Biochemical markers of liver fibrosis: a comparison with historical features in patients with chronic hepatitis C. Am J Gastroenterol. 2002;97:2419-25 pubmed
    ..This index is more accurate than an index of historical features, the addition of which to the existing index was not helpful. ..
  14. Levashina E, Moita L, Blandin S, Vriend G, Lagueux M, Kafatos F. Conserved role of a complement-like protein in phagocytosis revealed by dsRNA knockout in cultured cells of the mosquito, Anopheles gambiae. Cell. 2001;104:709-18 pubmed
    ..This evidence of a complement-like function in a protostome animal adds substantially to the accumulating evidence of a common ancestry of immune defenses in insects and vertebrates. ..
  15. Blacker D, Wilcox M, Laird N, Rodes L, Horvath S, Go R, et al. Alpha-2 macroglobulin is genetically associated with Alzheimer disease. Nat Genet. 1998;19:357-60 pubmed
  16. Ramos A, Duschak V, Gerez de Burgos N, Barboza M, Remedi M, Vides M, et al. Trypanosoma cruzi: cruzipain and membrane-bound cysteine proteinase isoform(s) interacts with human alpha(2)-macroglobulin and pregnancy zone protein. Exp Parasitol. 2002;100:121-30 pubmed
    ..The present study suggests that both human alpha-macroglobulin inhibitors could prevent or minimize harmful action of cruzipain on host's molecules and hypothetically regulate parasite functions controlled by cruzipain. ..
  17. Kristensen T, Moestrup S, Gliemann J, Bendtsen L, Sand O, Sottrup Jensen L. Evidence that the newly cloned low-density-lipoprotein receptor related protein (LRP) is the alpha 2-macroglobulin receptor. FEBS Lett. 1990;276:151-5 pubmed
    ..It is suggested that LRP is the functional receptor for alpha 2-macroglobulin-proteinase complexes (alpha 2MR) and in addition may have as yet unsettled functions in lipoprotein metabolism. ..
  18. van Goor H, Diamond J, Ding G, Kaysen G. Alpha macroglobulins and the low-density-lipoprotein-related protein/alpha-2-macroglobulin receptor in experimental renal fibrosis. Exp Nephrol. 1999;7:35-43 pubmed
    ..The alpha macroglobulins alpha-2-macroglobulin (alpha2M) and alpha-1-inhibitor 3 (alpha1I3) are proteinase inhibitors, including ..
  19. Cvirn G, Gallistl S, Koestenberger M, Kutschera J, Leschnik B, Muntean W. Alpha 2-macroglobulin enhances prothrombin activation and thrombin potential by inhibiting the anticoagulant protein C/protein S system in cord and adult plasma. Thromb Res. 2002;105:433-9 pubmed
    ..Therefore, elevated levels of a2-M might restrict the up-regulation of the APC/PS pathway. ..
  20. Liao H, Cianciolo G, Staats H, Scearce R, Lapple D, Stauffer S, et al. Increased immunogenicity of HIV envelope subunit complexed with alpha2-macroglobulin when combined with monophosphoryl lipid A and GM-CSF. Vaccine. 2002;20:2396-403 pubmed
  21. Nielsen K, Holtet T, Etzerodt M, Moestrup S, Gliemann J, Sottrup Jensen L, et al. Identification of residues in alpha-macroglobulins important for binding to the alpha2-macroglobulin receptor/Low density lipoprotein receptor-related protein. J Biol Chem. 1996;271:12909-12 pubmed
    ..From this result and mutational evidence from other ligands for the alpha2-macroglobulin receptor, a tentative sequence motif for receptor binding is proposed. ..
  22. Strickland D, Ashcom J, Williams S, Burgess W, Migliorini M, Argraves W. Sequence identity between the alpha 2-macroglobulin receptor and low density lipoprotein receptor-related protein suggests that this molecule is a multifunctional receptor. J Biol Chem. 1990;265:17401-4 pubmed
  23. Miyoshi S, Kawata K, Tomochika K, Shinoda S, Yamamoto S. The C-terminal domain promotes the hemorrhagic damage caused by Vibrio vulnificus metalloprotease. Toxicon. 2001;39:1883-6 pubmed
    ..These findings indicate that the C-terminal 10-kDa polypeptide, the substrate-binding domain mediating the effective binding to protein substrates, functions to augment the hemorrhagic reaction of VVP. ..
  24. Westwood M, Aplin J, Collinge I, Gill A, White A, Gibson J. alpha 2-Macroglobulin: a new component in the insulin-like growth factor/insulin-like growth factor binding protein-1 axis. J Biol Chem. 2001;276:41668-74 pubmed
    ..In line with its role in regulating the clearance and activity of other growth factors, we predict that alpha(2)M has a novel and important role in controlling the transport and biological activity of IGFs. ..
  25. Tsiouris J, Mehta P, Patti P, Madrid R, Raguthu S, Barshatzky M, et al. Alpha2 macroglobulin elevation without an acute phase response in depressed adults with Down's syndrome: implications. J Intellect Disabil Res. 2000;44 ( Pt 6):644-53 pubmed
    ..Further studies are needed to confirm that alpha2M elevation is specific to depression and that it might provide a helpful marker for the diagnosis of depression in people with ID. ..
  26. Hashimoto Y, Jiang H, Niikura T, Ito Y, Hagiwara A, Umezawa K, et al. Neuronal apoptosis by apolipoprotein E4 through low-density lipoprotein receptor-related protein and heterotrimeric GTPases. J Neurosci. 2000;20:8401-9 pubmed
  27. Enghild J, Salvesen G, Brew K, Nagase H. Interaction of human rheumatoid synovial collagenase (matrix metalloproteinase 1) and stromelysin (matrix metalloproteinase 3) with human alpha 2-macroglobulin and chicken ovostatin. Binding kinetics and identification of matrix metalloproteinase cle. J Biol Chem. 1989;264:8779-85 pubmed
    ..These results suggest that alpha 2M may play an important role in regulating the activities of matrix metalloproteinases in the extracellular space. ..
  28. Armstrong P, Quigley J. Alpha2-macroglobulin: an evolutionarily conserved arm of the innate immune system. Dev Comp Immunol. 1999;23:375-90 pubmed
  29. Herz J, Goldstein J, Strickland D, Ho Y, Brown M. 39-kDa protein modulates binding of ligands to low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor. J Biol Chem. 1991;266:21232-8 pubmed
    ..A potential in vivo role of the 39-kDa protein is to modulate the uptake of apoE-enriched lipoproteins and activated alpha 2-macroglobulin in hepatic and extrahepatic tissues. ..
  30. Huang W, Dolmer K, Liao X, Gettins P. Localization of basic residues required for receptor binding to the single alpha-helix of the receptor binding domain of human alpha2-macroglobulin. Protein Sci. 1998;7:2602-12 pubmed
    ..Secondary structure predictions of other alpha-macroglobulins show the conservation of this alpha-helix and suggest an important role for this helix and for basic residues within it for receptor binding. ..
  31. Rasmussen M, M ller H, Bj rck L. Protein GRAB of streptococcus pyogenes regulates proteolysis at the bacterial surface by binding alpha2-macroglobulin. J Biol Chem. 1999;274:15336-44 pubmed
    ..This regulation of proteolytic activity at the bacterial surface should affect the host-microbe relation during S. pyogenes infections...
  32. Umans L, Serneels L, Overbergh L, Lorent K, Van Leuven F, Van den Berghe H. Targeted inactivation of the mouse alpha 2-macroglobulin gene. J Biol Chem. 1995;270:19778-85 pubmed
    ..Thus, murinoglobulin appears as the major proteinase inhibitor around partum, obviously solicited to a much greater extend in alpha 2-macroglobulin-deficient mice. ..
  33. Sottrup Jensen L, Sand O, Kristensen L, Fey G. The alpha-macroglobulin bait region. Sequence diversity and localization of cleavage sites for proteinases in five mammalian alpha-macroglobulins. J Biol Chem. 1989;264:15781-9 pubmed
    ..Possible structural features of the widely different bait regions and their role in the mechanism of activation are discussed. ..
  34. Umans L, Serneels L, Overbergh L, Stas L, Van Leuven F. alpha2-macroglobulin- and murinoglobulin-1- deficient mice. A mouse model for acute pancreatitis. Am J Pathol. 1999;155:983-93 pubmed
    ..Mice deficient in MAM and/or MUG thus offer new experimental models for defining in vivo the role of the macroglobulins in pancreatitis and in other normal and pathological processes. ..
  35. Imbert Bismut F, Ratziu V, Pieroni L, Charlotte F, Benhamou Y, Poynard T. Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study. Lancet. 2001;357:1069-75 pubmed
    ..60 to 1.00 (34% [115] of all patients). A combination of basic serum markers could be used to substantially reduce the number of liver biopsies done in patients with chronic HCV infection. ..
  36. Poynard T, Imbert Bismut F, Ratziu V, Chevret S, Jardel C, Moussalli J, et al. Biochemical markers of liver fibrosis in patients infected by hepatitis C virus: longitudinal validation in a randomized trial. J Viral Hepat. 2002;9:128-33 pubmed
    ..32 +/- 0.03 at 72 weeks; P=0.05). No significant differences were observed for hyaluronic acid.Hence, this fibrosis index could be used as a surrogate marker of the antifibrotic effect of treatments in patients with chronic hepatitis C. ..
  37. Kusashio K, Shimizu H, Kimura F, Yoshidome H, Ohtsuka M, Kato A, et al. Effect of excessive acute-phase response on liver regeneration after partial hepatectomy in rats. Hepatogastroenterology. 2009;56:824-8 pubmed
  38. Ieko M, Naito S, Yoshida M, Kanazawa K, Mizukami K, Sato H, et al. Plasma soluble fibrin monomer complex as a marker of coronary thrombotic events in patients with acute myocardial infarction. Tohoku J Exp Med. 2009;219:25-31 pubmed
    ..Measuring plasma FMC may be useful for early diagnosis of MI recurrence and deciding primary treatment. ..
  39. Song H, Jia L, Zuo X, Jia J. Association between haplotype -88G/25G in A2M with Alzheimer's disease. Neurosci Lett. 2010;479:143-5 pubmed publisher
    ..77, 95%CI 1.06-2.96, P=0.027). Our study supports that haplotype -88G/25G might play a protective role in the development of SAD, and the protective effects of -88G and 25G were independent of APOEvarepsilon4 allele. ..
  40. Nakao M, Kato Unoki Y, Nakahara M, Mutsuro J, Somamoto T. Diversified components of the bony fish complement system: more genes for robuster innate defense?. Adv Exp Med Biol. 2006;586:121-38 pubmed
  41. Lakshminarayanan R, Li Y, Janatpour K, Beckett L, Jialal I. Detection by immunofixation of M proteins in hypogammaglobulinemic patients with normal serum protein electrophoresis results. Am J Clin Pathol. 2007;127:746-51 pubmed
    ..We recommend reflex IFE testing in patients with hypogammaglobulinemia with a normal SPE pattern if any of the following are present: elevated alpha2- globulin/alpha1-globulin ratio, low hemoglobin level, and elevated creatinine level. ..
  42. Thiele L, Diederichs J, Reszka R, Merkle H, Walter E. Competitive adsorption of serum proteins at microparticles affects phagocytosis by dendritic cells. Biomaterials. 2003;24:1409-18 pubmed
  43. Khan S, Khan F. Oxidized caprine alpha-2-macroglobulin: damaged but not completely dysfunctional. Biochim Biophys Acta. 2004;1674:139-48 pubmed
    ..It is proposed that inhibition of alpha2M activity may be due to oxidation of essential residues of the inhibitor and/or structural rearrangement of the subunits. ..
  44. Zappia M, Manna I, Serra P, Cittadella R, Andreoli V, La Russa A, et al. Increased risk for Alzheimer disease with the interaction of MPO and A2M polymorphisms. Arch Neurol. 2004;61:341-4 pubmed
    ..The MPO and A2M polymorphisms are associated with sporadic AD in southern Italy. Moreover, a genomic interaction between these polymorphisms increases the risk of the development of AD. ..
  45. Ngo Y, Munteanu M, Messous D, Charlotte F, Imbert Bismut F, Thabut D, et al. A prospective analysis of the prognostic value of biomarkers (FibroTest) in patients with chronic hepatitis C. Clin Chem. 2006;52:1887-96 pubmed
    ..001) in multivariate analyses after taking into account histology, treatment, alcohol consumption, and HIV coinfection. The FibroTest measurement of HCV biomarkers has a 5-year prognostic value similar to that of liver biopsy. ..
  46. Mihailovic M, Dinić S, Bogojevic D, Ivanovic Matic S, Uskoković A, Arambasić J, et al. Nuclear localization and binding affinity of STAT5b for the alpha(2)-macroglobulin gene promoter during rat liver development and the acute-phase response. Acta Biochim Pol. 2007;54:331-40 pubmed
    ..We conclude that developmental-stage differences in the mechanisms that determine STAT5b nuclear localization contribute to its activity in vivo. ..
  47. Tchetverikov I, Kraan M, van El B, Hanemaaijer R, DeGroot J, Huizinga T. Leflunomide and methotrexate reduce levels of activated matrix metalloproteinases in complexes with alpha2 macroglobulin in serum of rheumatoid arthritis patients. Ann Rheum Dis. 2008;67:128-30 pubmed
    ..The results show that systemic levels of activated MMPs are reduced in RA patients upon exposure to leflunomide or methotrexate. ..
  48. d Arondel C, Munteanu M, Moussalli J, Thibault V, Naveau S, Simon A, et al. A prospective assessment of an 'a la carte' regimen of PEG-interferon alpha2b and ribavirin combination in patients with chronic hepatitis C using biochemical markers. J Viral Hepat. 2006;13:182-9 pubmed
    ..It achieves a 73% SVR and a significant decrease in fibrosis and activity as estimated by biochemical markers. ..
  49. Haines J, Schnetz Boutaud N, Schmidt S, Scott W, Agarwal A, Postel E, et al. Functional candidate genes in age-related macular degeneration: significant association with VEGF, VLDLR, and LRP6. Invest Ophthalmol Vis Sci. 2006;47:329-35 pubmed
    ..02) datasets. VLDLR showed evidence of association in both the family based (P = 0.03) and case-control (P = 0.01) datasets. These data suggest that LRP6, VEGF, and VLDLR may play a role in the risk of developing AMD. ..
  50. Demirag B, Sarisozen B, Durak K, Bilgen O, Ozturk C. The effect of alpha-2 macroglobulin on the healing of ruptured anterior cruciate ligament in rabbits. Connect Tissue Res. 2004;45:23-7 pubmed
    ..001). At the end of this study, we concluded that the necessary conditions for the healing and repair of ruptured anterior cruciate ligament could exist if the enzymatic and biological environments were under control. ..
  51. Boukhettala N, Ibrahim A, Aziz M, Vuichoud J, Saudan K, Blum S, et al. A diet containing whey protein, free glutamine, and transforming growth factor-beta ameliorates nutritional outcome and intestinal mucositis during repeated chemotherapeutic challenges in rats. J Nutr. 2010;140:799-805 pubmed publisher
    ..A diet containing whey proteins, glutamine, and TGFbeta improves nutritional outcome by limiting the reduction of fat free mass and reduces intestinal mucositis during repeated chemotherapeutic challenges in rats. ..
  52. Andersson M, Jonsson U, Olsson A. A slow form of alpha-2-macroglobulin in diseased and healthy dogs. J Comp Pathol. 2002;127:37-44 pubmed
    ..This may lead to a delayed clearance of protease and inflammatory mediators from the circulation. Slow A2M was predominantly found in diseased dogs, especially in the Labrador retriever. ..
  53. Pau E, Alonso Muriel I, Gomez R, Novella E, Ruiz A, Garcia Velasco J, et al. Plasma levels of soluble vascular endothelial growth factor receptor-1 may determine the onset of early and late ovarian hyperstimulation syndrome. Hum Reprod. 2006;21:1453-60 pubmed
    ..In E- and L-OHSS, the ability to secrete sVEGFR-1 and bind VEGF seems to be the determinant factor in OHSS. f-VEGF acts locally in the ovary. ..