VAMP8/endobrevin is Overexpressed in Hyperreactive Human Platelets: Suggested Role for Platelet MicroRNA

Overview

Journal J Thromb Haemost

Publisher Elsevier

Specialty Hematology

Date 2009 Dec 1

PMID 19943878

Citations 80

Authors

A A Kondkar

M S Bray

S M Leal

S Nagalla

D J Liu

Y Jin

J F Dong

Q Ren

S W Whiteheart

C Shaw

P F Bray

Affiliations

Soon will be listed here.

Abstract

Background: Variation in platelet reactivity contributes to disorders of hemostasis and thrombosis, but the molecular mechanisms are not well understood.

Objectives: To discover associations between interindividual platelet variability and the responsible platelet genes, and to begin to define the molecular mechanisms altering platelet gene expression.

Subjects/methods: Two hundred and eighty-eight healthy subjects were phenotyped for platelet responsiveness. Platelet RNA from subjects demonstrating hyperreactivity (n=18) and hyporeactivity (n=11) was used to screen the human transcriptome.

Results: Distinctly different mRNA profiles were observed between subjects with differing platelet reactivity. Increased levels of mRNA for VAMP8/endobrevin, a critical v-SNARE involved in platelet granule secretion, were associated with platelet hyperreactivity (Q=0.0275). Validation studies of microarray results showed 4.8-fold higher mean VAMP8 mRNA levels in hyperreactive than hyporeactive platelets (P=0.0023). VAMP8 protein levels varied 13-fold among platelets from these normal subjects, and were 2.5-fold higher in hyperreactive platelets (P=0.05). Among our cohort of 288 subjects, a VAMP8 single-nucleotide polymorphism (rs1010) was associated with platelet reactivity in an age-dependent manner (P<0.003). MicroRNA-96 was predicted to bind to the 3'-untranslated regionof VAMP8 mRNA and was detected in platelets. Overexpression of microRNA-96 in VAMP8-expressing cell lines caused a dose-dependent decrease in VAMP8 protein and mRNA, suggesting a role in VAMP8 mRNA degradation.

Conclusions: These findings support a role for VAMP8/endobrevin in the heterogeneity of platelet reactivity, and suggest a role for microRNA-96 in the regulation of VAMP8 expression.

Citing Articles

Platelet-enriched microRNAs as novel biomarkers in atherosclerotic and cardiovascular disease patients.

Masoudikabir P, Shirazy M, Taghizadeh F, Gheydari M, Hamidpour M ARYA Atheroscler. 2024; 20(4):47-67.

PMID: 39717424 PMC: 11663285. DOI: 10.48305/arya.2024.41664.2898.

RUNX1 isoforms regulate RUNX1 and target genes differentially in platelets-megakaryocytes: association with clinical cardiovascular events.

Guan L, Voora D, Myers R, Del Carpio-Cano F, Rao A J Thromb Haemost. 2024; 22(12):3581-3598.

PMID: 39181539 PMC: 11608153. DOI: 10.1016/j.jtha.2024.07.032.

RUNX1 Isoforms Regulate RUNX1 and Target-Genes Differentially in Platelets-Megakaryocytes: Association with Clinical Cardiovascular Events.

Guan L, Voora D, Myers R, Del Carpio-Cano F, Rao A bioRxiv. 2024; .

PMID: 38948740 PMC: 11212995. DOI: 10.1101/2024.06.18.599563.

Unveiling Atherosclerotic Plaque Heterogeneity and SPP1/VCAN Macrophage Subtype Prognostic Significance Through Integrative Single-Cell and Bulk-Seq Analysis.

Xu X, Qiu F, Yang M, Liu X, Tao S, Zheng B J Inflamm Res. 2024; 17:2399-2426.

PMID: 38681071 PMC: 11055562. DOI: 10.2147/JIR.S454505.

Inflammatory microRNAs in cardiovascular pathology: another brick in the wall.

Zapata-Martinez L, Aguila S, de Los Reyes-Garcia A, Carrillo-Tornel S, Lozano M, Gonzalez-Conejero R Front Immunol. 2023; 14:1196104.

PMID: 37275892 PMC: 10233054. DOI: 10.3389/fimmu.2023.1196104.

References

Jacobson K, Ishihara A, Inman R . Lateral diffusion of proteins in membranes. Annu Rev Physiol. 1987; 49:163-75. DOI: 10.1146/annurev.ph.49.030187.001115. View

Yee D, Sun C, Bergeron A, Dong J, Bray P . Aggregometry detects platelet hyperreactivity in healthy individuals. Blood. 2005; 106(8):2723-9. PMC: 1634759. DOI: 10.1182/blood-2005-03-1290. View

Gnatenko D, Dunn J, McCorkle S, Weissmann D, Perrotta P, Bahou W . Transcript profiling of human platelets using microarray and serial analysis of gene expression. Blood. 2002; 101(6):2285-93. DOI: 10.1182/blood-2002-09-2797. View

Bray P . Platelet hyperreactivity: predictive and intrinsic properties. Hematol Oncol Clin North Am. 2007; 21(4):633-45, v-vi. PMC: 1986652. DOI: 10.1016/j.hoc.2007.06.002. View

Weyrich A, Schwertz H, Kraiss L, Zimmerman G . Protein synthesis by platelets: historical and new perspectives. J Thromb Haemost. 2008; 7(2):241-6. PMC: 3027201. DOI: 10.1111/j.1538-7836.2008.03211.x. View

Dalmasso C, Broet P, Moreau T . A simple procedure for estimating the false discovery rate. Bioinformatics. 2004; 21(5):660-8. DOI: 10.1093/bioinformatics/bti063. View

Shiffman D, Rowland C, Louie J, Luke M, Bare L, Bolonick J . Gene variants of VAMP8 and HNRPUL1 are associated with early-onset myocardial infarction. Arterioscler Thromb Vasc Biol. 2006; 26(7):1613-8. DOI: 10.1161/01.ATV.0000226543.77214.e4. View

Shi B, Sepp-Lorenzino L, Prisco M, Linsley P, DeAngelis T, Baserga R . Micro RNA 145 targets the insulin receptor substrate-1 and inhibits the growth of colon cancer cells. J Biol Chem. 2007; 282(45):32582-90. DOI: 10.1074/jbc.M702806200. View

Ren Q, Ye S, Whiteheart S . The platelet release reaction: just when you thought platelet secretion was simple. Curr Opin Hematol. 2008; 15(5):537-41. PMC: 2665692. DOI: 10.1097/MOH.0b013e328309ec74. View

10.

Raghavachari N, Xu X, Harris A, Villagra J, Logun C, Barb J . Amplified expression profiling of platelet transcriptome reveals changes in arginine metabolic pathways in patients with sickle cell disease. Circulation. 2007; 115(12):1551-62. PMC: 2225987. DOI: 10.1161/CIRCULATIONAHA.106.658641. View

11.

McRedmond J, Park S, Reilly D, Coppinger J, Maguire P, Shields D . Integration of proteomics and genomics in platelets: a profile of platelet proteins and platelet-specific genes. Mol Cell Proteomics. 2003; 3(2):133-44. DOI: 10.1074/mcp.M300063-MCP200. View

12.

ODonnell C, Larson M, Feng D, Sutherland P, Lindpaintner K, Myers R . Genetic and environmental contributions to platelet aggregation: the Framingham heart study. Circulation. 2001; 103(25):3051-6. DOI: 10.1161/01.cir.103.25.3051. View

13.

Carthew R, Sontheimer E . Origins and Mechanisms of miRNAs and siRNAs. Cell. 2009; 136(4):642-55. PMC: 2675692. DOI: 10.1016/j.cell.2009.01.035. View

14.

Polgar J, Chung S, Reed G . Vesicle-associated membrane protein 3 (VAMP-3) and VAMP-8 are present in human platelets and are required for granule secretion. Blood. 2002; 100(3):1081-3. DOI: 10.1182/blood.v100.3.1081. View

15.

Bray M, Shaw C, Moore M, Garcia R, Zanquetta M, Durgan D . Disruption of the circadian clock within the cardiomyocyte influences myocardial contractile function, metabolism, and gene expression. Am J Physiol Heart Circ Physiol. 2007; 294(2):H1036-47. DOI: 10.1152/ajpheart.01291.2007. View

16.

Jones C, Garner S, Angenent W, Bernard A, Berzuini C, Burns P . Mapping the platelet profile for functional genomic studies and demonstration of the effect size of the GP6 locus. J Thromb Haemost. 2007; 5(8):1756-65. DOI: 10.1111/j.1538-7836.2007.02632.x. View

17.

Ma A, Abrams C . Pleckstrin induces cytoskeletal reorganization via a Rac-dependent pathway. J Biol Chem. 1999; 274(40):28730-5. DOI: 10.1074/jbc.274.40.28730. View

18.

Denis M, Tolley N, Bunting M, Schwertz H, Jiang H, Lindemann S . Escaping the nuclear confines: signal-dependent pre-mRNA splicing in anucleate platelets. Cell. 2005; 122(3):379-91. PMC: 4401993. DOI: 10.1016/j.cell.2005.06.015. View

19.

Ibanez-Ventoso C, Yang M, Guo S, Robins H, Padgett R, Driscoll M . Modulated microRNA expression during adult lifespan in Caenorhabditis elegans. Aging Cell. 2006; 5(3):235-46. DOI: 10.1111/j.1474-9726.2006.00210.x. View

20.

Vicente V, Kostel P, Ruggeri Z . Isolation and functional characterization of the von Willebrand factor-binding domain located between residues His1-Arg293 of the alpha-chain of glycoprotein Ib. J Biol Chem. 1988; 263(34):18473-9. View