scholarly journals A Platelet Function Modulator of Thrombin Activation Is Causally Linked to Cardiovascular Disease and Affects PAR4 Receptor Signaling

2020 ◽  
Vol 107 (2) ◽  
pp. 211-221 ◽  
Author(s):  
Benjamin A.T. Rodriguez ◽  
Arunoday Bhan ◽  
Andrew Beswick ◽  
Peter C. Elwood ◽  
Teemu J. Niiranen ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Platelet Function ◽  
Receptor Signaling ◽  
Thrombin Activation

scholarly journals MicroRNA as Biomarkers for Platelet Function and Maturity in Patients with Cardiovascular Disease

2021 ◽  
Author(s):  
Oliver Buchhave Pedersen ◽  
Erik Lerkevang Grove ◽  
Steen Dalby Kristensen ◽  
Peter H. Nissen ◽  
Anne-Mette Hvas
Keyword(s):  
Cardiovascular Disease ◽  
Platelet Function ◽  
Assessment Tool ◽  
Platelet Reactivity ◽  
Thrombus Formation ◽  
Quality Assessment Tool ◽  
Treatment And Prevention ◽  
Increased Risk ◽  
Meta Analyses ◽  
Potential Use

AbstractPatients with cardiovascular disease (CVD) are at increased risk of suffering myocardial infarction. Platelets are key players in thrombus formation and, therefore, antiplatelet therapy is crucial in the treatment and prevention of CVD. MicroRNAs (miRs) may hold the potential as biomarkers for platelet function and maturity. This systematic review was conducted using the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). To identify studies investigating the association between miRs and platelet function and maturity in patients with CVD, PubMed and Embase were searched on October 13 and December 13, 2020 without time boundaries. Risk of bias was evaluated using a standardized quality assessment tool. Of the 16 included studies, 6 studies were rated “good” and 10 studies were rated “fair.” In total, 45 miRs correlated significantly with platelet function or maturity (rho ranging from –0.68 to 0.38, all p < 0.05) or differed significantly between patients with high platelet reactivity and patients with low platelet reactivity (p-values ranging from 0.0001 to 0.05). Only four miRs were investigated in more than two studies, namely miR-223, miR-126, miR-21 and miR-150. Only one study reported on the association between miRs and platelet maturity. In conclusion, a total of 45 miRs were associated with platelet function or maturity in patients with CVD, with miR-223 and miR-126 being the most frequently investigated. However, the majority of the miRs were only investigated in one study. More data are needed on the potential use of miRs as biomarkers for platelet function and maturity in CVD patients.

Abstract 516: Chromosome 18p Deletion Inhibits Platelet Aggregation

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Andrew D Meyer ◽  
Anjana Raghunath ◽  
Patricia Heard ◽  
Jannine Cody
Keyword(s):  
Cardiovascular Disease ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Disease Modeling ◽  
Significant Risk ◽  
The United States ◽  
Gene Copy ◽  
Impedance Aggregometry ◽  
Significant Difference ◽  
Normal Controls

Inappropriate platelet function is a significant risk factor for cardiovascular disease, the leading cause of death in the United States. Although abnormal platelet function has a strong genetic component, very few human genes have been linked to platelet function. Mice with a homozygous deletion of EMILIN2 (Elastin Microfibril Interface Located Protein2) gene, located on Chromosome 18p, have a significant decrease in platelet function and clot formation. However, deletion or inactivation of only one copy of a gene is most relevant to human disease modeling. Our hypothesis is that blood samples from people with single 18p deletions that include EMILIN2 will have decreased platelet function compared to healthy individuals. We conducted a case-control study of nine adult individuals with chromosome 18p deletions matched with healthy men and women (n=20). Routine coagulation measurements were performed on a STAGO STA-R instrument. Platelet aggregation was measured with whole blood impedance aggregometry and Thromboelastography with PlateletMapping using the manufacturers’ protocols. There was no significant difference in platelet count, prothrombin time, partial thromboplastin time, d-dimer, or fibrinogen between individuals with a single 18p gene copy number and normal controls. However, platelet aggregation was impaired in individuals with 18p deletions compared to normal controls in response to collagen and arachidonic acid (ASPI), respectively ( p <0.0001, Figure 1). Moreover, Thromboelastography with PlateletMapping was decreased in individuals with 18p deletions compared to normal controls for ADP and ASPI, ( p <0.001). Individuals with one copy of 18p have decrease platelet function compared to normal controls. These results identify a novel human genetic loci linked to a specific phenotype of platelet function. Future will studies will determine if this gene can be used for diagnostic or therapeutics for cardiovascular disease.

scholarly journals Alteration of platelet function in dogs mediated by interleukin-6

Blood ◽  
1994 ◽  
Vol 83 (2) ◽  
pp. 398-403
Author(s):  
J Peng ◽  
P Friese ◽  
JN George ◽  
GL Dale ◽  
SA Burstein
Keyword(s):  
Monoclonal Antibody ◽  
Platelet Activation ◽  
Platelet Function ◽  
Interleukin 6 ◽  
Platelet Activating Factor ◽  
Platelet Surface ◽  
Thrombin Activation ◽  
Dog Blood ◽  
And Control ◽  
Twofold Decrease

To determine if interleukin-6 (IL-6) administration influences platelet function, platelet activation was analyzed sequentially in IL-6-treated (80 micrograms/kg/d) and control dogs. Platelet activation was determined in whole blood by flow cytometry by quantitating the binding of a monoclonal antibody to platelet surface P-selectin after stimulation with graded doses of thrombin. Administration of IL-6 resulted in a twofold decrease in the thrombin concentration required for induction of half-maximal P-selectin expression (ED50) compared with control animals. The ED50 returned to normal after cessation of IL- 6 administration. As measured by P-selectin expression, enhanced responsiveness to the strong agonist platelet activating factor (PAF) was also observed in the IL-6-treated dogs. IL-6 had no effect on the susceptibility of platelets to thrombin activation when incubated with anticoagulated dog blood. The data show that, in addition to augmenting the platelet count in normal dogs, IL-6 enhances the sensitivity of platelets to activation in response to thrombin and PAF.

Platelets, Obesity, and the Metabolic Syndrome

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. SCI-34-SCI-34
Author(s):  
Jane Freedman
Keyword(s):  
Gene Expression ◽  
Cardiovascular Disease ◽  
Platelet Function ◽  
Conflicts Of Interest ◽  
Innate Immune ◽  
Metabolic Dysfunction ◽  
Reverse Transcription Pcr ◽  
The Metabolic Syndrome ◽  
Excess Adiposity ◽  
All Cause Mortality

Abstract Abstract SCI-34 Cardiovascular disease continues to be the major cause of morbidity and mortality in North America and a growing problem in many other parts of the world. The risk of premature atherosclerosis and cardiovascular events rises with increasing obesity and excess adiposity has been linked to increased all-cause mortality. Current estimates show that one in four ischemic heart disease events are attributable to excess weight. Inflammation of adipose tissue orchestrated by monocyte/macrophage infiltration and overproduction of proinflammatory and proatherogenic cytokines may mediate metabolic dysfunction and vascular disease in human obesity. Importantly, obesity has been associated with increased cardiovascular disease as well as enhanced platelet function and thrombosis. We recently measured expression of 48 genes by high-throughput quantitative reverse transcription PCR (qRT-PCR) in over 2250 participants of the Framingham Offspring and Omni minority cohorts (FHS) using RNA from isolated platelets and found that specific inflammatory transcripts including ICAM1, IL1R, IFNG, IL6, COX2, TNF, TLR2, and TLR4 were significantly and positively associated with higher body mass index (BMI) by regression analysis. With the additional measurement of 196 genes, the data has remained extraordinarily consistent. Other cardiovascular risk factors rarely associate with platelet gene expression and BMI remains specifically associated with inflammatory transcripts related to the NFkB-innate immune and inflammatory pathways. These surprising data led to the question: Why would the anucleate platelet have gene expression changes specifically in the setting of increased BMI and can this powerful clinical association be explored using both pre-clinical and clinical studies to find new targets for disease and define new mechanisms for platelet function beyond thrombosis? Disclosures: No relevant conflicts of interest to declare.

scholarly journals Effects of electronic cigarette on platelet and vascular function after one month of use

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
I Ikonomidis ◽  
K Katogiannis ◽  
G Kostelli ◽  
K Kourea ◽  
E Kyriakou ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Smoking Cessation ◽  
Arterial Stiffness ◽  
Cigarette Smoking ◽  
Platelet Function ◽  
Tobacco Smoking ◽  
Vascular Function ◽  
Augmentation Index ◽  
Electronic Cigarette ◽  
Nicotine Concentration

Abstract Background and aims Smoking is a major factor that contributes to the development of cardiovascular disease. Smoking cessation delays progress of coronary artery disease. Electronic cigarette is proposed as a bridge to smoking cessation. We examined its effects on platelet function after 1 month of use compared to tobacco smoking. Patients and methods 40 current smokers (mean age 48 years±5) without cardiovascular disease were randomized to smoke either a conventional cigarette (conv-cig) or an electronic cigarette (e-cig) (electronic cigarette fluid with nicotine concentration of 12 mg/dL) for one month. All subjects smoked an electronic cigarette with nicotine concentration 12 mg/dL for one month. Measurements were performed at baseline and after one month of smoking the conventional or electronic cigarette. We measured a) perfused boundary region (PBR) of the sublingual arterial micro vessels (range 5–25 micrometers), a marker inversely related with glycocalyx thickness, b) pulse wave velocity (PWV), central systolic blood pressure (cSBP) and augmentation index (AIx), c) platelet function by two different methods, namely the novel Platelet Function Analyzer PFA-100 and the traditional Light Transmission Aggregometry (LTA) d) the exhaled CO level (parts per million-ppm) as a smoking status marker; and e) the plasma malondialdehyde (MDA) levels, as an oxidative stress burden index. Results After 1 month of electronic smoking, we did not observe any significant change in platelet function and arterial stiffness (p&gt;0.05 for all markers) with the exception of a reduction of MDA (1.22±0.1 vs 1.09±0.1 μmol/L, p=0.03) and exhaled CO; 14.9±0.7 vs 5.9±0.7 ppm, p&lt;0.001. Conversely, after continuation of conventional cigarette smoking for a month, platelet function was further impaired as assessed by PFA [125,5±31,1 vs 152,35±51,4 U, p=0.047) and by LTA (epinephrine as stimulator) [59,8%±16,1 vs 35,6%±19.1, p&lt;0.001] and markers of arterial stiffness were deteriorated, as assessed by PWV (9,5±2,8 vs 10,3±2,9, p=0,028) and by Aixc (8,36±35,9 vs 30,4±21,6, p=0,004). Conclusions Electronic Cigarette smoking has a neutral effect on platelet function and arterial stiffness markers compared to conventional tobacco smoking which further deteriorates platelet and vascular function during one moth of use. Funding Acknowledgement Type of funding source: None

Platelet Function and Antiplatelet Therapy in Cardiovascular Disease: Implications of Genetic Polymorphisms

2011 ◽  
Vol 9 (4) ◽  
pp. 479-489 ◽  
Author(s):  
Jayashree Shanker ◽  
Armen Yuri Gasparyan ◽  
George D. Kitas ◽  
Vijay V. Kakkar
Keyword(s):  
Cardiovascular Disease ◽  
Antiplatelet Therapy ◽  
Genetic Polymorphisms ◽  
Platelet Function

Abstract 3477: Platelet Hyper-responsiveness in Aspirin-Treated Patients with Clinical Cardiovascular Disease Compared to Matched High Risk Controls

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Nauder Faraday ◽  
Lisa R Yanek ◽  
Taryn F Moy ◽  
Dhananjay Vaidya ◽  
J. E Herrera-Galeano ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
High Risk ◽  
Platelet Function ◽  
Ex Vivo ◽  
Platelet Reactivity ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Increased Risk

Background: Platelet hyper-responsiveness to activating stimuli during aspirin (ASA) therapy may discriminate between high risk subjects who have developed acute thrombotic cardiovascular disease (CVD) events (coronary disease and stroke) and those who are at increased risk but are disease free. We hypothesized that subjects with documented CVD would have greater platelet reactivity on ASA therapy compared to matched high risk non-CVD subjects. Methods: Subjects (N=228; 61 +/− 8 yrs, 69% male, 60% white) were selected from families with known CVD; 114 had prevalent CVD and were matched on age, sex, and race to 114 apparently healthy controls with risk factors but without clinical CVD. CVD risk factors were measured and therapy adherence was determined by questionnaires. Platelet reactivity on 81 mg ASA/day was determined by whole blood (WB) aggregometry, platelet function analyzer (PFA) closure time, thromboxane B2 (TxB2) release ex vivo , and urinary excretion of 11-dehyrothromboxane B2 (Tx-M) in vivo . Results. CVD cases had greater platelet reactivity by all measures, both unadjusted, and adjusted for age, sex, race and adherence (Table ). Multivariable adjustment for cardiac risk factors and statin therapy eliminated case-control differences for Tx-M, but not for the ex vivo measures of platelet activation. ASA therapy duration in CVD subjects (8.8 +/− 6.2 yrs) was not related to platelet function. Conclusions: Greater residual platelet reactivity exists during ASA therapy in CVD subjects compared to matched high risk controls, even controlling for CVD risk factors and adherence to therapy. The data suggest that platelet hyper-responsiveness during ASA chemoprophylaxis may differentiate patients with CVD from those who are at risk for CVD, but have not developed it. Platelet hyper-responsiveness may be an intrinsic property of CVD, related to as yet unidentified environmental or genetic factors.

Sign in / Sign up

Export Citation Format

Share Document