GPVI levels in platelets: relationship to platelet function at high shear

Best, Denise

doi:10.1182/blood-2003-01-0231

Cited by 120 publications

(114 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There are two common alleles of GPVI ("a" and "b"), which differ by five amino acids and occur at population frequencies of 0.85 and 0.13, respectively (26). Individuals homozygous for the b allele have a lower GPVI density on their platelet surface and reduced thrombogenicity in response to collagen (26,27). It is thus possible that the above-mentioned family with a mutation in P3H2 carries the low-frequency b allele of GPVI, which allowed them to escape the maternal platelet aggregation in response to non-3-hydroxylated type IV collagen.…”

Section: Discussionmentioning

confidence: 99%

Biological role of prolyl 3-hydroxylation in type IV collagen

Pokidysheva

Boudko

Vranka

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Collagens constitute nearly 30% of all proteins in our body. Type IV collagen is a major and crucial component of basement membranes. Collagen chains undergo several posttranslational modifications that are indispensable for proper collagen function. One of these modifications, prolyl 3-hydroxylation, is accomplished by a family of prolyl 3-hydroxylases (P3H1, P3H2, and P3H3). The present study shows that P3H2-null mice are embryonic-lethal by embryonic day 8.5. The mechanism of the unexpectedly early lethality involves the interaction of non-3-hydroxylated embryonic type IV collagen with the maternal platelet-specific glycoprotein VI (GPVI). This interaction results in maternal platelet aggregation, thrombosis of the maternal blood, and death of the embryo. The phenotype is completely rescued by producing double KOs of P3H2 and GPVI. Double nulls are viable and fertile. Under normal conditions, subendothelial collagens bear the GPVI-binding sites that initiate platelet aggregation upon blood exposure during injuries. In type IV collagen, these sites are normally 3-hydroxylated. Thus, prolyl 3-hydroxylation of type IV collagen has an important function preventing maternal platelet aggregation in response to the early developing embryo. A unique link between blood coagulation and the ECM is established. The newly described mechanism may elucidate some unexplained fetal losses in humans, where thrombosis is often observed at the maternal/fetal interface. Moreover, epigenetic silencing of P3H2 in breast cancers implies that the interaction between GPVI and non-3-hydroxylated type IV collagen might also play a role in the progression of malignant tumors and metastasis.C ollagens constitute nearly 30% of all proteins in our body (1).Among the 29 collagen types, type IV collagen is a major and crucial component of basement membranes (2). Different collagen types assemble into different structures. Examples of these structures are fibrils (collagen types I, II, and III) and networks (collagen types IV and VI) (1). Proper posttranslational modifications of collagen chains are critical for ultimate quaternary structure formation and function. Posttranslational modifications of collagen include prolyl 4-hydroxylation, lysyl hydroxylation and glycosylation, and prolyl 3-hydroxylation (3). The prolyl 3-hydroxylase family (P3H1, P3H2, and P3H3) is responsible for the process of prolyl 3-hydroxylation. These enzymes modify specific prolines in GlyProHyp [Hyp is 4(R)-hydroxyproline] sequences into 3(S)-hydroxyproline (3Hyp) (4). Although prolyl 4-hydroxylation occurs at almost every Yaa position proline in the Gly-Xaa-Yaa repeated sequence of collagen, prolyl 3-hydroxylation happens only at a few specific Xaa position prolines.P3H1 is the main enzyme modifying type I collagen. Mutations in P3H1 have been found to cause severe osteogenesis imperfecta (OI) in both humans and mice (5, 6). The causative molecular mechanism of the OI phenotype remains speculative. Limited information is available about the substrate specificity of ...

show abstract

Section: Discussionmentioning

confidence: 99%

Biological role of prolyl 3-hydroxylation in type IV collagen

Pokidysheva

Boudko

Vranka

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Concerning platelet membrane glycoproteins, it has been reported that genetic polymorphisms of GPIa, 10 GPIba, 11 GPIIIa 12,13 and GPVI 14 influence the efficacy of aspirin or platelet responsiveness. Furthermore, Halushka et al 15 reported the association of platelet aggregation with genetic mutation of COX-1, Papafili et al 16 the association with genetic mutation of COX-2, Higuchi et al 17 the association with genetic mutation of TXA 2 receptors (TP), Stafforini et al 18 the association with genetic mutation of platelet activating factor acetylhydrolase (PAFAH) and Undas et al 19 the association with genetic mutation of coagulation factor XIII (FXIII).…”

Section: Introductionmentioning

confidence: 99%

Exploratory aspirin resistance trial in healthy Japanese volunteers (J-ART) using platelet aggregation as a measure of thrombogenicity

et al. 2007

View full text Add to dashboard Cite

“…HPA-2 has been found to be in linkage disequilibrium with another GP Iba polymorphism, namely, the variable number of tandem repeats (VNTR) [22,23]. The VNTR polymorphism results from a 13-amino acid sequence repeat in the macroglycopeptide region of GP Iba [24,25]. There are four variants of the VNTR polymorphism known as A, B, C, and D in order of decreasing molecular mass.…”

Section: Discussionmentioning

confidence: 99%

Platelet functional implications of glycoprotein Ibα polymorphisms in African Americans

Williams¹,

Ng’alla²,

Vaidya³

2006

American J Hematol

View full text Add to dashboard Cite

The platelet glycoprotein Iba is crucial in the binding of platelets to Von Willebrand Factor within areas of high stress. A single nucleotide polymorphism of GP Iba gives rise to the Ko a (HPA-2b) and the -5C Kozak polymorphism. The presence of these polymorphisms has been associated with an increased risk for atherothrombotic disease. The Ko a polymorphism has been shown to have a higher prevalence in African Americans compared to American Caucasians. However, very little is known regarding any functional consequences of these platelet polymorphisms in African Americans. We assessed the prevalence of the Ko and -5C Kozak polymorphisms in a population of both African American and American Caucasian patients with and without CAD and determined whether there were platelet functional consequences in both groups. We studied 99 patients of which 22 were African American and 77 were American Caucasian. Aggregations were performed and shear induced platelet plug formation was tested using a platelet function analyzer. The HPA-2b allele was significantly higher in African Americans when compared to Caucasians (P ¼ 0.001). Genotype frequencies of the -5C Kozak polymorphism were not significantly different between the two groups. We found no differences in platelet aggregation in African Americans who were either heterozygous or homozygous for the HPA-2b allele or the -5C Kozak allele when compared to American Caucasians of the same category. We found no significant differences in PFA-100 testing. We conclude from our study that these polymorphisms do not lead to altered platelet function in African Americans. Am. J. Hematol. 82:15-22, 2007. V V C 2006 Wiley-Liss, Inc.

show abstract

GPVI levels in platelets: relationship to platelet function at high shear

Cited by 120 publications

References 55 publications

Biological role of prolyl 3-hydroxylation in type IV collagen

Biological role of prolyl 3-hydroxylation in type IV collagen

Exploratory aspirin resistance trial in healthy Japanese volunteers (J-ART) using platelet aggregation as a measure of thrombogenicity

Platelet functional implications of glycoprotein Ibα polymorphisms in African Americans

Contact Info

Product

Resources

About