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Angewandte Chemie (International Ed. in... Sep 2021Cells transmit piconewton forces to receptors to mediate processes such as migration and immune recognition. A major challenge in quantifying such forces is the sparsity...
Cells transmit piconewton forces to receptors to mediate processes such as migration and immune recognition. A major challenge in quantifying such forces is the sparsity of cell mechanical events. Accordingly, molecular tension is typically quantified with high resolution fluorescence microscopy, which hinders widespread adoption and application. Here, we report a mechanically triggered hybridization chain reaction (mechano-HCR) that allows chemical amplification of mechanical events. The amplification is triggered when a cell receptor mechanically denatures a duplex revealing a cryptic initiator to activate the HCR reaction in situ. Importantly, mechano-HCR enables direct readout of pN forces using a plate reader. We leverage this capability and measured mechano-IC for aspirin, Y-27632, and eptifibatide. Given that cell mechanical phenotypes are of clinical importance, mechano-HCR may offer a convenient route for drug discovery, personalized medicine, and disease diagnosis.
Topics: Aspirin; Eptifibatide; Humans; Nucleic Acid Hybridization
PubMed: 34242462
DOI: 10.1002/anie.202107660 -
Current Hypertension Reports Nov 2016Endothelial dysfunction is intimately related to the development of various cardiovascular diseases, including hypertension, and is often used as a target for... (Review)
Review
PURPOSE OF REVIEW
Endothelial dysfunction is intimately related to the development of various cardiovascular diseases, including hypertension, and is often used as a target for pharmacological treatment. The scope of this review is to assess effects of aspirin on endothelial function and their clinical implication in arterial hypertension.
RECENT FINDINGS
Emerging data indicate the role of platelets in the development of vascular inflammation due to the release of proinflammatory mediators, for example, triggered largely by thromboxane. Vascular inflammation further promotes oxidative stress, diminished synthesis of vasodilators, proaggregatory and procoagulant state. These changes translate into vasoconstriction, impaired circulation and thrombotic complications. Aspirin inhibits thromboxane synthesis, abolishes platelets activation and acetylates enzymes switching them to the synthesis of anti-inflammatory substances. Aspirin pleiotropic effects have not been fully elucidated yet. In secondary prevention studies, the decrease in cardiovascular events with aspirin outweighs bleeding risks, but this is not the case in primary prevention settings. Ongoing trials will provide more evidence on whether to expand the use of aspirin or stay within current recommendations.
Topics: Animals; Aspirin; Clinical Trials as Topic; Endothelium, Vascular; Humans; Hypertension; Thrombosis; Vasoconstriction
PubMed: 27787837
DOI: 10.1007/s11906-016-0688-8 -
JPMA. the Journal of the Pakistan... Apr 2023To determine the role of low-dose aspirin in preventing preeclampsia for previously hypertensive pregnant women. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the role of low-dose aspirin in preventing preeclampsia for previously hypertensive pregnant women.
METHODS
The meta-analysis was conducted from February to May 2021 and comprised search on PubMed and Cochrane Library databases for randomised controlled trials consisting of previously hypertensive women aged 18-55 years, aspirin dosage range 60-100mg, and a comparison between aspirin and placebo groups. Duration of intervention till the end of gestation, the dosage of aspirin given, risk ratios or odds ratio with the confidence intervals, and preeclampsia were the main variables recorded. Data was analysed using RevMan 5.4.
RESULTS
Of the 144 articles found, 4(%) were included, having 2238 participants. Pooled estimates revealed that aspirin, compared to placebo, did not significantly reduce the manifestation of preeclampsia (p=0.06). Besides, heterogeneity between the different trials was moderate at 59%.
CONCLUSIONS
Aspirin was not found to substantially diminish the risk of incidence of preeclampsia, but it did show some beneficial effects. .
Topics: Female; Pregnancy; Humans; Aspirin; Pre-Eclampsia; Platelet Aggregation Inhibitors; Pregnant Women; Hypertension
PubMed: 37051996
DOI: 10.47391/JPMA.5544 -
Family Medicine and Community Health Apr 2021To review the pathophysiology of COVID-19 disease, potential aspirin targets on this pathogenesis and the potential role of aspirin in patients with COVID-19. (Review)
Review
OBJECTIVES
To review the pathophysiology of COVID-19 disease, potential aspirin targets on this pathogenesis and the potential role of aspirin in patients with COVID-19.
DESIGN
Narrative review.
SETTING
The online databases PubMed, OVID Medline and Cochrane Library were searched using relevant headlines from 1 January 2016 to 1 January 2021. International guidelines from relevant societies, journals and forums were also assessed for relevance.
PARTICIPANTS
Not applicable.
RESULTS
A review of the selected literature revealed that clinical deterioration in COVID-19 is attributed to the interplay between endothelial dysfunction, coagulopathy and dysregulated inflammation. Aspirin has anti-inflammatory effects, antiplatelet aggregation, anticoagulant properties as well as pleiotropic effects on endothelial function. During the COVID-19 pandemic, low-dose aspirin is used effectively in secondary prevention of atherosclerotic cardiovascular disease, prevention of venous thromboembolism after total hip or knee replacement, prevention of pre-eclampsia and postdischarge treatment for multisystem inflammatory syndrome in children. Prehospital low-dose aspirin therapy may reduce the risk of intensive care unit admission and mechanical ventilation in hospitalised patients with COVID-19, whereas aspirin association with mortality is still debatable.
CONCLUSION
The authors recommend a low-dose aspirin regimen for primary prevention of arterial thromboembolism in patients aged 40-70 years who are at high atherosclerotic cardiovascular disease risk, or an intermediate risk with a risk-enhancer and have a low risk of bleeding. Aspirin's protective roles in COVID-19 associated with acute lung injury, vascular thrombosis without previous cardiovascular disease and mortality need further randomised controlled trials to establish causal conclusions.
Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; COVID-19; Humans; Inflammation; Middle Aged; Practice Guidelines as Topic; Thromboembolism
PubMed: 33879541
DOI: 10.1136/fmch-2020-000741 -
Ultrasound in Obstetrics & Gynecology :... Jun 2023The mechanism by which aspirin prevents pre-eclampsia is poorly understood, and its effects on biomarkers throughout pregnancy are unknown. We aimed to investigate the... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
The mechanism by which aspirin prevents pre-eclampsia is poorly understood, and its effects on biomarkers throughout pregnancy are unknown. We aimed to investigate the effects of aspirin on mean arterial pressure (MAP) and mean uterine artery pulsatility index (UtA-PI) using repeated measures from women at increased risk of preterm pre-eclampsia.
METHODS
This was a longitudinal secondary analysis of the Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Pre-eclampsia Prevention (ASPRE) trial using repeated measures of MAP and UtA-PI. In the trial, 1620 women at increased risk of preterm pre-eclampsia were identified using the Fetal Medicine Foundation algorithm at 11 + 0 to 13 + 6 weeks, of whom 798 were randomly assigned to receive 150 mg/day aspirin and 822 were assigned to receive placebo daily from 11-14 weeks to 36 weeks of gestation or delivery, whichever came first. MAP and UtA-PI were measured at baseline and follow-up visits at 19-24, 32-34 and 36 weeks of gestation. Generalized additive mixed models with treatment by gestational age interaction terms were used to investigate the effects of aspirin on MAP and UtA-PI trajectories over time.
RESULTS
Among 798 participants in the aspirin group and 822 in the placebo group, there were 5951 MAP and 5942 UtA-PI measurements. Trajectories of raw and multiples of the median (MoM) values of MAP did not differ significantly between the two groups (MAP MoM analysis: P-value for treatment by gestational age interaction, 0.340). In contrast, trajectories of raw and MoM values of UtA-PI showed a significantly steeper decline in the aspirin group than in the placebo group, with the difference mainly driven by a more pronounced reduction before 20 weeks of gestation (UtA-PI MoM analysis: P-value for treatment by gestational age interaction, 0.006).
CONCLUSIONS
In women at increased risk of preterm pre-eclampsia, 150 mg/day aspirin initiated in the first trimester does not affect MAP but is associated with a significant decrease in mean UtA-PI, particularly before 20 weeks of gestation. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Aspirin; Pre-Eclampsia; Arterial Pressure; Uterine Artery; Placenta Growth Factor; Pregnancy Trimester, First; Biomarkers; Pulsatile Flow
PubMed: 37058400
DOI: 10.1002/uog.26222 -
BMC Medical Genomics Jun 2024Mediators, genomic and epigenomic characteristics involving in metabolism of arachidonic acid by cyclooxygenase (COX) and lipoxygenase (ALOX) and hepatic activation of...
BACKGROUND
Mediators, genomic and epigenomic characteristics involving in metabolism of arachidonic acid by cyclooxygenase (COX) and lipoxygenase (ALOX) and hepatic activation of clopidogrel have been individually suggested as factors associated with resistance against aspirin and clopidogrel. The present multi-center prospective cohort study evaluated whether the mediators, genomic and epigenomic characteristics participating in arachidonic acid metabolism and clopidogrel activation could be factors that improve the prediction of the aspirin and clopidogrel resistance in addition to cardiovascular risks.
METHODS
We enrolled 988 patients with transient ischemic attack and ischemic stroke who were evaluated for a recurrence of ischemic stroke to confirm clinical resistance, and measured aspirin (ARU) and P2Y12 reaction units (PRU) using VerifyNow to assess laboratory resistance 12 weeks after aspirin and clopidogrel administration. We investigated whether mediators, genotypes, and promoter methylation of genes involved in COX and ALOX metabolisms and clopidogrel activation could synergistically improve the prediction of ischemic stroke recurrence and the ARU and PRU levels by integrating to the established cardiovascular risk factors.
RESULTS
The logistic model to predict the recurrence used thromboxane A synthase 1 (TXAS1, rs41708) A/A genotype and ALOX12 promoter methylation as independent variables, and, improved sensitivity of recurrence prediction from 3.4% before to 13.8% after adding the mediators, genomic and epigenomic variables to the cardiovascular risks. The linear model we used to predict the ARU level included leukotriene B4, COX2 (rs20417) C/G and thromboxane A2 receptor (rs1131882) A/A genotypes with the addition of COX1 and ALOX15 promoter methylations as variables. The linear PRU prediction model included G/A and prostaglandin I receptor (rs4987262) G/A genotypes, COX2 and TXAS1 promoter methylation, as well as cytochrome P450 2C19*2 (rs4244285) A/A, G/A, and *3 (rs4986893) A/A genotypes as variables. The linear models for predicting ARU (r = 0.291, R = 0.033, p < 0.01) and PRU (r = 0.503, R = 0.210, p < 0.001) levels had improved prediction performance after adding the genomic and epigenomic variables to the cardiovascular risks.
CONCLUSIONS
This study demonstrates that different mediators, genomic and epigenomic characteristics of arachidonic acid metabolism and clopidogrel activation synergistically improved the prediction of the aspirin and clopidogrel resistance together with the cardiovascular risk factors.
TRIAL REGISTRATION
URL: https://www.
CLINICALTRIALS
gov ; Unique identifier: NCT03823274.
Topics: Humans; Clopidogrel; Male; Female; Aspirin; Drug Resistance; Middle Aged; Aged; Epigenomics; Genomics; Prospective Studies; Platelet Aggregation Inhibitors; DNA Methylation
PubMed: 38902747
DOI: 10.1186/s12920-024-01936-1 -
Canadian Journal of Physiology and... Mar 2019Inflammation has been linked to several complications in pregnancy, including pregnancy loss. Due to its anti-inflammatory properties, aspirin, a widely available and... (Review)
Review
Inflammation has been linked to several complications in pregnancy, including pregnancy loss. Due to its anti-inflammatory properties, aspirin, a widely available and inexpensive therapy, has potential to help mitigate the negative effects of inflammation along the reproductive pathway. Therefore, the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial was designed to elucidate whether preconception-initiated daily low-dose aspirin would increase the live birth rate in women with 1-2 prior pregnancy losses and no infertility diagnosis and attempting unassisted conception. Here, we present an overview of the collected findings. Low-dose aspirin was associated with an increased live birth rate among women with a single loss at <20 weeks gestation within the past year. When stratified by tertile of C-reactive protein (CRP), a biomarker of inflammation, treatment with aspirin restored a decrement in the live birth rate in women in the highest CRP tertile (relative risk 1.35, 95% confidence interval 1.08-1.67), increasing to similar rates as women of the lower and mid-CRP tertiles. The same effect modification by inflammation status was observed when examining the effect of low-dose aspirin on offspring sex ratio. These results suggest that inflammation plays an important role in reproduction, and that chronic, low-grade inflammation may be amenable to aspirin treatment.
Topics: Animals; Aspirin; Female; Humans; Inflammation; Pregnancy; Pregnancy Outcome; Reproduction
PubMed: 30562044
DOI: 10.1139/cjpp-2018-0368 -
Clinical Medicine & Research Dec 2014Aspirin therapy is well-accepted as an agent for the secondary prevention of cardiovascular events and current guidelines also define a role for aspirin in primary... (Review)
Review
Aspirin therapy is well-accepted as an agent for the secondary prevention of cardiovascular events and current guidelines also define a role for aspirin in primary prevention. In this review, we describe the seminal trials of aspirin use in the context of current guidelines, discuss factors that may influence the effectiveness of aspirin therapy for cardiovascular disease prevention, and briefly examine patterns of use. The body of evidence supports a role for aspirin in both secondary and primary prevention of cardiovascular events in selected population groups, but practice patterns may be suboptimal. As a simple and inexpensive prophylactic measure for cardiovascular disease, aspirin use should be carefully considered in all at-risk adult patients, and further measures, including patient education, are necessary to ensure its proper use.
Topics: Aspirin; Cardiovascular Diseases; Humans; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Primary Prevention; Secondary Prevention
PubMed: 24573704
DOI: 10.3121/cmr.2013.1197 -
Cancer Epidemiology, Biomarkers &... Mar 2021Evidence for aspirin's chemopreventative properties on colorectal cancer (CRC) is substantial, but its mechanism of action is not well-understood. We combined a...
BACKGROUND
Evidence for aspirin's chemopreventative properties on colorectal cancer (CRC) is substantial, but its mechanism of action is not well-understood. We combined a proteomic approach with Mendelian randomization (MR) to identify possible new aspirin targets that decrease CRC risk.
METHODS
Human colorectal adenoma cells (RG/C2) were treated with aspirin (24 hours) and a stable isotope labeling with amino acids in cell culture (SILAC) based proteomics approach identified altered protein expression. Protein quantitative trait loci (pQTLs) from INTERVAL ( = 3,301) and expression QTLs (eQTLs) from the eQTLGen Consortium ( = 31,684) were used as genetic proxies for protein and mRNA expression levels. Two-sample MR of mRNA/protein expression on CRC risk was performed using eQTL/pQTL data combined with CRC genetic summary data from the Colon Cancer Family Registry (CCFR), Colorectal Transdisciplinary (CORECT), Genetics and Epidemiology of Colorectal Cancer (GECCO) consortia and UK Biobank (55,168 cases and 65,160 controls).
RESULTS
Altered expression was detected for 125/5886 proteins. Of these, aspirin decreased MCM6, RRM2, and ARFIP2 expression, and MR analysis showed that a standard deviation increase in mRNA/protein expression was associated with increased CRC risk (OR: 1.08, 95% CI, 1.03-1.13; OR: 3.33, 95% CI, 2.46-4.50; and OR: 1.15, 95% CI, 1.02-1.29, respectively).
CONCLUSIONS
MCM6 and RRM2 are involved in DNA repair whereby reduced expression may lead to increased DNA aberrations and ultimately cancer cell death, whereas ARFIP2 is involved in actin cytoskeletal regulation, indicating a possible role in aspirin's reduction of metastasis.
IMPACT
Our approach has shown how laboratory experiments and population-based approaches can combine to identify aspirin-targeted proteins possibly affecting CRC risk.
Topics: Aspirin; Colorectal Neoplasms; Humans; Mendelian Randomization Analysis; Proteomics; Risk Factors
PubMed: 33318029
DOI: 10.1158/1055-9965.EPI-20-1176 -
Association of metformin, aspirin, and cancer incidence with mortality risk in adults with diabetes.JNCI Cancer Spectrum Mar 2023Metformin and aspirin are commonly co-prescribed to people with diabetes. Metformin may prevent cancer, but in older people (over 70 years), aspirin has been found to... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Metformin and aspirin are commonly co-prescribed to people with diabetes. Metformin may prevent cancer, but in older people (over 70 years), aspirin has been found to increase cancer mortality. This study examined whether metformin reduces cancer mortality and incidence in older people with diabetes; it used randomization to 100 mg aspirin or placebo in the ASPirin in Reducing Events in the Elderly (ASPREE) trial to quantify aspirin's impact on metformin users.
METHODS
Analysis included community-dwelling ASPREE participants (aged ≥70 years, or ≥65 years for members of US minority populations) with diabetes. Diabetes was defined as a fasting blood glucose level greater than 125 mg/dL, self-report of diabetes, or antidiabetic medication use. Cox proportional hazards regression models were used to analyze the association of metformin and a metformin-aspirin interaction with cancer incidence and mortality, with adjustment for confounders.
RESULTS
Of 2045 participants with diabetes at enrollment, 965 were concurrently using metformin. Metformin was associated with a reduced cancer incidence risk (adjusted hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.51 to 0.90), but no conclusive benefit for cancer mortality (adjusted HR = 0.72, 95% CI = 0.43 to 1.19). Metformin users randomized to aspirin had greater risk of cancer mortality compared with placebo (HR = 2.53, 95% CI = 1.18 to 5.43), but no effect was seen for cancer incidence (HR = 1.11, 95% CI = 0.75 to 1.64). The possible effect modification of aspirin on cancer mortality, however, was not statistically significant (interaction P = .11).
CONCLUSIONS
In community-dwelling older adults with diabetes, metformin use was associated with reduced cancer incidence. Increased cancer mortality risk in metformin users randomized to aspirin warrants further investigation.
ASPREE TRIAL REGISTRATION
ClinicalTrials.gov ID NCT01038583.
Topics: Aged; Humans; Metformin; Aspirin; Diabetes Mellitus, Type 2; Incidence; Neoplasms
PubMed: 36857596
DOI: 10.1093/jncics/pkad017