Molecular and Functional Differences Induced in Thrombospondin-1 by the Single Nucleotide Polymorphism Associated with the Risk of Premature, Familial Myocardial Infarction

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2004 Mar 10

PMID 15007078

Citations 15

Authors

Natalya V Narizhneva

Vicky J Byers-Ward

Martin J Quinn

Frank J Zidar

Edward F Plow

Eric J Topol

Tatiana V Byzova

Affiliations

Soon will be listed here.

Abstract

A serine (Ser-700) amino acid rather than an asparagine (Asn-700) at residue 700 of thrombospondin-1 has been linked to an increased risk for development of premature, familial heart attacks. We now have identified both functional and structural differences between the Ser-700 and Asn-700 thrombospondin-1 variants. The Ser-700 variant increased the rate and extent of platelet aggregation and showed increased surface expression on platelets compared with the Asn-700 variant. These differences could be ascribed to an enhanced interaction of the Ser-700 variant with fibrinogen on the platelet surface and are consistent with a prothrombotic phenotype in Ser-700 individuals. The Ser-700 variant thrombospondin-1 was conformationally more labile than the Asn-700 variant as demonstrated by increased susceptibility to proteolytic digestion and enhanced susceptibility to unfolding by denaturants. These data suggest a potential molecular and cellular basis for a genetic risk factor associated with early onset myocardial infarction.

Citing Articles

Thrombospondins: Conserved mediators and modulators of metazoan extracellular matrix.

Adams J Int J Exp Pathol. 2024; 105(5):136-169.

PMID: 39267379 PMC: 11574667. DOI: 10.1111/iep.12517.

Thrombospondin-1, BIM and CFH polymorphisms and response to anti-VEGF treatment in neovascular age- related macular degeneration patients.

Sorenson C, Gurel Z, Song Y, Peterson K, Blodi B, Sheibani N PLoS One. 2024; 19(2):e0297135.

PMID: 38408093 PMC: 10896504. DOI: 10.1371/journal.pone.0297135.

Pathogenesis of glaucoma: Extracellular matrix dysfunction in the trabecular meshwork-A review.

Keller K, Peters D Clin Exp Ophthalmol. 2022; 50(2):163-182.

PMID: 35037377 PMC: 9199435. DOI: 10.1111/ceo.14027.

Thrombospondin-1 in maladaptive aging responses: a concept whose time has come.

Isenberg J, Roberts D Am J Physiol Cell Physiol. 2020; 319(1):C45-C63.

PMID: 32374675 PMC: 7468894. DOI: 10.1152/ajpcell.00089.2020.

Neutrophil-Mediated Proteolysis of Thrombospondin-1 Promotes Platelet Adhesion and String Formation.

Seif K, Alidzanovic L, Tischler B, Ibrahim N, Zagrapan B, Rauscher S Thromb Haemost. 2018; 118(12):2074-2085.

PMID: 30419595 PMC: 6298231. DOI: 10.1055/s-0038-1675229.

References

Boekholdt S, Trip M, Peters R, Engelen M, Boer J, Feskens E . Thrombospondin-2 polymorphism is associated with a reduced risk of premature myocardial infarction. Arterioscler Thromb Vasc Biol. 2002; 22(12):e24-7. DOI: 10.1161/01.atv.0000046235.22451.66. View

Yamada Y, Izawa H, Ichihara S, Takatsu F, Ishihara H, Hirayama H . Prediction of the risk of myocardial infarction from polymorphisms in candidate genes. N Engl J Med. 2002; 347(24):1916-23. DOI: 10.1056/NEJMoa021445. View

Huo Y, Schober A, Forlow S, Smith D, Hyman M, Jung S . Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein E. Nat Med. 2002; 9(1):61-7. DOI: 10.1038/nm810. View

Hang L, Hsia T, Chen W, Chen H, Tsai F . TAP1 gene AccI polymorphism is associated with atopic bronchial asthma. J Clin Lab Anal. 2003; 17(2):57-60. PMC: 6807779. DOI: 10.1002/jcla.10068. View

Hannah B, Misenheimer T, Annis D, Mosher D . A polymorphism in thrombospondin-1 associated with familial premature coronary heart disease causes a local change in conformation of the Ca2+-binding repeats. J Biol Chem. 2003; 278(11):8929-34. DOI: 10.1074/jbc.m211185200. View

Stryer L . Fluorescence spectroscopy of proteins. Science. 1968; 162(3853):526-33. DOI: 10.1126/science.162.3853.526. View

Adler A, Greenfield N, Fasman G . Circular dichroism and optical rotatory dispersion of proteins and polypeptides. Methods Enzymol. 1973; 27:675-735. DOI: 10.1016/s0076-6879(73)27030-1. View

Hagen I . Effects of thrombin on washed, human platelets: changes in the subcellular fractions. Biochim Biophys Acta. 1975; 392(2):242-54. DOI: 10.1016/0304-4165(75)90006-9. View

Lawler J, Chao F, Fang P . Observation of a high molecular weight platelet protein released by thrombin. Thromb Haemost. 1977; 37(2):355-7. View

10.

Lawler J, Slayter H, Coligan J . Isolation and characterization of a high molecular weight glycoprotein from human blood platelets. J Biol Chem. 1978; 253(23):8609-16. View

11.

Marguerie G, Plow E, Edgington T . Human platelets possess an inducible and saturable receptor specific for fibrinogen. J Biol Chem. 1979; 254(12):5357-63. View

12.

Marguerie G, Edgington T, Plow E . Interaction of fibrinogen with its platelet receptor as part of a multistep reaction in ADP-induced platelet aggregation. J Biol Chem. 1980; 255(1):154-61. View

13.

Plow E, Marguerie G . Inhibition of fibrinogen binding to human platelets by the tetrapeptide glycyl-L-prolyl-L-arginyl-L-proline. Proc Natl Acad Sci U S A. 1982; 79(12):3711-5. PMC: 346496. DOI: 10.1073/pnas.79.12.3711. View

14.

Lahav J, Lawler J, Gimbrone M . Thrombospondin interactions with fibronectin and fibrinogen. Mutual inhibition in binding. Eur J Biochem. 1984; 145(1):151-6. DOI: 10.1111/j.1432-1033.1984.tb08534.x. View

15.

Lawler J, Derick L, Connolly J, Chen J, Chao F . The structure of human platelet thrombospondin. J Biol Chem. 1985; 260(6):3762-72. View

16.

Dixit V, Haverstick D, ORourke K, Hennessy S, Grant G, Santoro S . A monoclonal antibody against human thrombospondin inhibits platelet aggregation. Proc Natl Acad Sci U S A. 1985; 82(10):3472-6. PMC: 397798. DOI: 10.1073/pnas.82.10.3472. View

17.

Stenberg P, McEver R, Shuman M, Jacques Y, BAINTON D . A platelet alpha-granule membrane protein (GMP-140) is expressed on the plasma membrane after activation. J Cell Biol. 1985; 101(3):880-6. PMC: 2113718. DOI: 10.1083/jcb.101.3.880. View

18.

Wolff R, Plow E, Ginsberg M . Interaction of thrombospondin with resting and stimulated human platelets. J Biol Chem. 1986; 261(15):6840-6. View

19.

Aiken M, Ginsberg M, Plow E . Divalent cation-dependent and independent surface expression of thrombospondin on thrombin-stimulated human platelets. Blood. 1987; 69(1):58-64. View

20.

Aiken M, Ginsberg M, Plow E . Mechanisms for expression of thrombospondin on the platelet cell surface. Semin Thromb Hemost. 1987; 13(3):307-16. DOI: 10.1055/s-2007-1003506. View