Platelet dysfunction in vascular pathologies and how can it be treated

Alexandru, Nicoleta; Popov, Doina; Georgescu, Adelina

doi:10.1016/j.thromres.2011.09.026

Cited by 56 publications

(36 citation statements)

References 143 publications

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“…The functional role of platelets in CAD has been investigated by many researchers in great detail in the past as well as in the present (Alexandru et al 2012) (Ombrello et al 2010). Platelets play a well-defined role in both hemostasis and atherothrombosis by releasing important mediators (Nesbitt et al 2006).…”

Section: Discussionmentioning

confidence: 99%

Frequency of single nucleotide platelet receptor gene polymorphism (P2Y12-i744T>C) in coronary artery disease patients among Tamilian population

et al. 2017

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Several factors contribute to the development of coronary artery disease (CAD). Adenosine diphosphate (ADP) activated P2Y12 receptor also plays a key role in platelet activation and aggregation. It has been found that common variation in the P2Y12 gene was associated with increased platelet aggregation resulting in adverse cardiovascular outcomes. Thus, polymorphisms in the ADP receptor P2Y12 may contribute to the development of CAD. This study aims to determine the frequency distribution of platelet receptor polymorphism P2Y12 (i744T>C) in Tamilian population and to predict its possible role in CAD. Three hundred seventyone subjects were recruited comprising of 221 healthy volunteers and 150 patients with CAD belonging to either sex, aged 18-60 years of Tamilian origin. Genomic DNA was extracted using phenol-chloroform method. Genotyping was done by PCR-RFLP (Polymerase chain reaction-restriction fragment length polymorphism). The C allele frequency of P2Y12 polymorphism in controls and cases was 8.4% and 17.7%, respectively. The TT, TC, and CC genotype frequencies in controls and cases were 83.7%, 15.8%, 0.5% and 66.7%, 31.3%, 2%, respectively. The genotype frequencies were in HardyWeinberg equilibrium. There was a significant association (p < 0.05) between the mutant genotypes of P2Y12 (i744T>C) polymorphism and risk of CAD. The odds ratio was found to be 2.6. The variant allele frequency of P2Y12-i744T>C was significantly different from other populations. There was a significant association between the mutant genotypes of P2Y12 (i744T>C) polymorphism and risk of developing CAD. Thus, the present study will emphasize on the relevance of pharmacogenetic testing of P2Y12 (i744T>C) receptor gene polymorphism in CAD patients.

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Section: Discussionmentioning

confidence: 99%

Frequency of single nucleotide platelet receptor gene polymorphism (P2Y12-i744T>C) in coronary artery disease patients among Tamilian population

et al. 2017

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“…We determined the possible role (41,42). In our study, BSA-AGEs were prepared as previously described (1). Cultured HUVECs were then treated with 5 mg/ml BSA-AGEs to initiate cell apoptosis.…”

Section: Platelet Mir-223 Promotes Huvec Apoptosis Induced By Ages VImentioning

confidence: 99%

“…In addition to maintaining hemostasis, platelets are also a key player in various pathologic processes, including inflammatory diseases such as arthritis and atherosclerosis (1). Platelets can be easily activated, leading to various inflammatory responses such as adhesion, secretion, and aggregation.…”

mentioning

confidence: 99%

Platelet-Secreted MicroRNA-223 Promotes Endothelial Cell Apoptosis Induced by Advanced Glycation End Products via Targeting the Insulin-like Growth Factor 1 Receptor

Pan

Liang

Liu

et al. 2014

The Journal of Immunology

209

177

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Platelets play a significant role in atherosclerosis, stroke, and asthma through active interaction with neutrophils, monocytes, and vascular endothelial cells. The mechanism underlying these intercellular interactions, however, is incompletely understood. In this study, we report that platelets can remotely modulate vascular endothelial cell apoptosis through releasing microRNA-223 (miR-223)–containing microvesicles (MVs). First, platelets expressed abundant miRNAs, and miR-223 had the highest level of expression. Platelet miR-223 and other miRNAs can be upregulated by the stimulation with thrombopoietin (TPO) or thrombin. Unlike leukocytes, platelets contained high levels of pre-miRNAs, and upregulation of mature platelet miRNAs by TPO was correlated with decreased pre-miRNAs. Second, under stimulation with TPO, platelets released a large amount of MVs, which also contain higher levels of miR-223. Elevation of miR-223 inside circulating platelet MVs (P-MVs) was also observed in plasma samples from patients with enteritis, hepatitis, nephritis, or atherosclerosis. Third, incubation of P-MVs with HUVECs, which had significantly lower levels of miR-223 than platelets, showed that P-MVs effectively delivered miR-223 into HUVECs. Finally, in HUVECs, exogenous platelet miR-223 decreased the level of insulin-like growth factor 1 receptor and thus promoted HUVEC apoptosis induced by advanced glycation end products. The proapoptotic effect of P-MVs on HUVECs was largely abolished by depleting cellular miR-223 using anti–miR-223 antisense oligonucleotide. In conclusion, our study presents the first evidence, to our knowledge, that platelet-released miR-223 promotes advanced glycation end product–induced vascular endothelial cell apoptosis via targeting insulin-like growth factor 1 receptor.

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“…It is difficult to presume, from a relatively small number of well designed and controlled human trials, how polyphenols improve the cardio-vascular function or the glucose homeostasis (Ostertag et al 2010;Alexandru et al 2012). Clinical studies which investigate the potential role of polyphenols in health and disease are difficult to design, as long-term studies are interfered by the treatment and the evolution of the disease.…”

Section: Reply From D Margina and M Iliementioning

confidence: 99%

“…Still, even if authors state that additional larger, longerduration and extensive trials are required to confirm the exact mechanism of cardiovascular benefits comong from polyphenols and their effects on glucose homeostasis and adipose tissue, incorporating plant foods that are rich in flavanols in the diet of healthy individuals could help to reduce cardio-vascular risk (Ostertag et al 2010;Alexandru et al 2012). …”

Section: Reply From D Margina and M Iliementioning

confidence: 99%