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Platelet Aggregation Response (platelet + aggregation_response)

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Medical Sciences	100%

Selected Abstracts

Platelet aggregation responses are critically regulated in vivo by endogenous nitric oxide but not by endothelial nitric oxide synthase

BRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2009
C Tymvios
Background and purpose:, Although exogenous nitric oxide (NO) clearly modifies platelet function, the role and the source of endogenous NO in vivo remain undefined. In addition, endothelial NO synthase (NOS-3) critically regulates vessel tone but its role in modulating platelet function is unclear. In this paper we have investigated the roles of endogenous NO and NOS-3 in regulating platelet function in vivo and determined the functional contribution made by platelet-derived NO. Experimental approach:, We used a mouse model for directly assessing platelet functional responses in situ in the presence of an intact vascular endothelium with supporting in vitro and molecular studies. Key results:, Acute NOS inhibition by N, -nitro-L-arginine methyl ester hydrochloride (L-NAME) enhanced platelet aggregatory responses to thrombin and platelets were shown to be regulated primarily by NO sources external to the platelet. Elevation of endogenous NOS inhibitors to mimic effects reported in patients with cardiovascular diseases did not enhance platelet responses. Platelet responsiveness following agonist stimulation was not modified in male or female NOS-3,/, mice but responses in NOS-3,/, mice were enhanced by L-NAME. Conclusions and implications:, Platelets are regulated by endogenous NO in vivo, primarily by NO originating from the environment external to the platelet with a negligible or undetectable role of platelet-derived NO. Raised levels of endogenous NOS inhibitors, as reported in a range of diseases were not, in isolation, sufficient to enhance platelet activity and NOS-3 is not essential for normal platelet function in vivo due to the presence of bioactive NO following deletion of NOS-3. [source]

Study of V1a vasopressin receptor gene single nucleotide polymorphisms in platelet vasopressin responsiveness

JOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 3 2006
Kazi N. Hasan
Abstract There is a significant heterogeneity among individuals in terms of platelet aggregation response to arginine vasopressin (AVP). The aim of this study was to evaluate whether four single nucleotide polymorphisms (SNPs) in the promoter region of vasopressin V1a receptor gene (V1aR) could be used as genetic markers for divergent platelet aggregation response to AVP. Seventeen of 33 subjects showed more than 60% of maximum platelet aggregation and were classified as responders. Sixteen were classified as nonresponders because they had less than 30% aggregation. In a preliminary study, V1aR gene sequences were determined in two responders and two nonresponders. We found four SNPs in the promoter region of the V1aR gene: ,6951G/A, ,4112A/T, ,3860T/C, and ,242C/T. In all 33 subjects the genotypes of four SNPs were determined using either polymerase chain reaction (PCR) with allele-specific primers or PCR followed by restriction-fragment length polymorphism (RFLP). There were no differences in the AVP-induced aggregation between the subjects with and without variant alleles of each four SNPs. The genotype frequencies of four SNPs of V1aR were almost identical between AVP responders and nonresponders. These results suggest that the four SNPs in the promoter region of the V1aR gene may not be useful as genetic markers for platelet aggregation heterogeneity. J. Clin. Lab. Anal. 20:87,92, 2006. © 2006 Wiley-Liss, Inc. [source]

Heritability of platelet function in families with premature coronary artery disease

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2007
P. F. BRAY
Summary.,Background:,Variations in platelet function among individuals may be related to differences in platelet-related genes. The major goal of our study was to estimate the contribution of inheritance to the variability in platelet function in unaffected individuals from white and African American families with premature coronary artery disease.Methods:,Platelet reactivity, in the absence of antiplatelet agents, was assessed by in vitro aggregation and the platelet function analyzer closure time. Heritability was estimated using a variance components model.Results:,Both white (n = 687) and African American (n = 321) subjects exhibited moderate to strong heritability (h2) for epinephrine- and adenosine diphosphate-induced aggregation (0.36,0.42 for white and >0.71 for African American subjects), but heritability for collagen-induced platelet aggregation in platelet-rich plasma was prominent only in African American subjects. Platelet lag phase after collagen stimulation was heritable in both groups (0.47,0.50). A limited genotype analysis demonstrated that the C825T polymorphism of GNB3 was associated with the platelet aggregation response to 2 ,M epinephrine, but the effect differed by race.Conclusions:,Considering the few and modest genetic effects reported to affect platelet function, our findings suggest the likely existence of undiscovered important genes that modify platelet reactivity, some of which affect multiple aspects of platelet biology. [source]