A5091566580- Antiplatelet Therapy and Cardiovascular Diseases
- Platelet Disorders and Treatments
- Inflammatory mediators and NSAID effects
- Venous Thromboembolism Diagnosis and Management
- Eicosanoids and Hypertension Pharmacology
- Nitric Oxide and Endothelin Effects
- Blood properties and coagulation
- SARS-CoV-2 and COVID-19 Research
- Sulfur Compounds in Biology
- Extracellular vesicles in disease
- Immunodeficiency and Autoimmune Disorders
- Pharmacology and Obesity Treatment
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Atrial Fibrillation Management and Outcomes
- Synthesis of β-Lactam Compounds
- Hormonal Regulation and Hypertension
- Cardiac Fibrosis and Remodeling
- Adenosine and Purinergic Signaling
- Cancer-related molecular mechanisms research
- Genetic Associations and Epidemiology
- High Altitude and Hypoxia
- Cystic Fibrosis Research Advances
- Renin-Angiotensin System Studies
- Blood groups and transfusion
- Estrogen and related hormone effects
Naval Research Laboratory Information Technology Division
2021-2024
National Heart Lung and Blood Institute
2020-2024
Framingham Heart Study
2020-2024
Queen Mary University of London
2014-2023
University of South Florida
2023
University of Massachusetts Lowell
2023
Framingham State University
2021-2022
Lung Institute
2018-2022
University of Toronto
2019
University Health Network
2019
Rationale: Platelets shed microRNAs (miRNAs). Plasma miRNAs change on platelet inhibition. It is unclear whether plasma miRNA levels correlate with function. Objective: To link small RNAs to reactivity. Methods and Results: Next-generation sequencing of in revealed 2 peaks at 22 23 32 33 nucleotides corresponding YRNAs, respectively. Among predominantly, fragments RNY4 RNY5 were detected. YRNAs measured 125 patients a history acute coronary syndrome who had undergone detailed assessment...
Significance Nonsteroidal antiinflammatory drugs (NSAIDs) work by inhibiting cyclooxygenase-2 (COX-2) induced at sites of inflammation. They are among the most widely used worldwide, but their cardiovascular side effects a major concern for patients, regulators, and industry. NSAID mediated inhibition constitutively expressed COX-2 present in discrete regions, including kidney. However, pathways driving constitutive remain poorly understood. The presented here defines these importantly shows...
Host genetic variants influence the susceptibility and severity of several infectious diseases, discovery associations with coronavirus disease 2019 (COVID-19) phenotypes could help to develop new therapeutic strategies decrease its burden. Between May 2020 June 2021, we used COVID-19 data released periodically by UK Biobank performed 65 genome-wide association studies in up 18 releases (n = 18,481 cases 2021), hospitalization 3,260), severe outcomes 1,244), deaths 1,104), stratified sex...
Aspirin together with thienopyridine P2Y12 inhibitors, commonly clopidogrel, is a cornerstone of antiplatelet therapy. However, many patients receiving this therapy display high on-treatment platelet reactivity, which major therapeutic hurdle to the prevention recurrent thrombotic events. The emergence uninhibited platelets after thrombopoiesis has been proposed as contributing factor reactivity. Here, we investigate influences turnover on aggregation in face different dual-antiplatelet...
Objective: Platelets are central to acute myocardial infarction (MI). How the platelet proteome is altered during MI unknown. We sought describe changes in and identify corresponding functional consequences. Approach Results: from patients experiencing ST-segment–elevation (STEMI) before 3 days after treatment (n=30) matched with severe stable coronary artery disease bypass grafting (n=25) underwent quantitative proteomic analysis. Elevations proteins S100A8 S100A9 were detected at time of...
Platelets circulate in the blood of healthy individuals for approximately 7-10 days regulated by finely balanced processes production and destruction. As platelets are anucleate we reasoned that their protein composition would change as they age this be linked to alterations structure function.To isolate different ages from test hypothesis changes content cause platelet function.Platelets were separated according thiazole orange fluorescence intensity a surrogate indicator mRNA so marker...
Platelet reactivity testing is important for the diagnosis of bleeding disorders, and increasingly to optimise anti-platelet therapy. Traditional light transmission aggregometry considered gold standard, whilst 96-well plate aggregometry, founded on similar principles, provides a higher throughput screening method. Despite widespread use both, methodologies outputs vary widely between laboratories. We report methodological approach towards providing standardised optical detection platelet...
Circulating platelets are constantly exposed to nitric oxide (NO) released from the vascular endothelium. This NO acts reduce platelet reactivity, and in so doing blunts aggregation thrombus formation. For successful hemostasis, activation must occur at sites of injury despite constant presence NO. As aggregate, they release secondary mediators that drive further aggregation. Particularly significant among these is ADP, which, acting through P2Y 12 receptors, strongly amplifies Platelet...
Cyclooxygenase 2 (COX)-2 is induced by bacterial and viral infections has complex, poorly understood roles in anti-pathogen immunity. Here, we use a knock-in luciferase reporter model to image Cox2 expression across range of tissues mice following treatment with the either prototypical pathogen-associated molecular pattern (PAMP), LPS, which activates Toll-like receptor (TLR)4, or poly(I:C), PAMP, TLR3. LPS all examined. In contrast, poly(I:C) elicited milder response, limited subset...
Trauma-induced coagulopathy (TIC) is a complex, multifactorial failure of hemostasis that occurs in 25% severely injured patients and results fourfold higher mortality. However, the role platelets this state remains poorly understood. We set out to identify molecular changes may underpin platelet dysfunction after major injury determine how they relate outcome. performed range hemostatic platelet-specific studies blood samples obtained from critically within 2 hours collected prospective...
Pre-menopausal females have a lower incidence of cardiovascular disease compared with age-matched males, implying differences in the mechanisms and pathways regulating vasoactivity. In small arteries, myogenic tone (constriction response to raised intraluminal pressure) is major determinant vascular resistance. Endothelium-derived dilators, particularly NO, tonically moderate and, because endothelium an important target for female sex hormones, we investigated whether NO-mediated moderation...
Fibrosis is a major contributor to organ disease for which no specific therapy available. MicroRNA-21 (miR-21) has been implicated in the fibrogenetic response, and inhibitors of miR-21 are currently undergoing clinical trials. Here, we explore how inhibition may attenuate fibrosis using proteomics approach. Transfection mimic or inhibitor murine cardiac fibroblasts revealed limited effects on extracellular matrix (ECM) protein secretion. Similarly, miR-21–null mouse hearts showed an...
Essentials•Platelet function testing in large populations is rare.•We performed 5 types of platelet tests on 3429 participants the Framingham Heart Study.•Different are unique, and so one cannot be substituted for another.•Sex, age, aspirin use significantly affect results, care must taken interpreting reference ranges.AbstractBackgroundAssessment key diagnosing bleeding disorders evaluating antiplatelet drug efficacy. However, there a prevailing "one-size-fits-all" approach interpretation...
In vivo platelet function is a product of intrinsic reactivity, modifiable by dual antiplatelet therapy (DAPT), and the extrinsic inhibitory endothelial mediators, nitric oxide (NO) prostacyclin (PGI2 ), that are powerfully potentiated P2Y12 receptor blockade. This implies for individual patients mediator production an important determinant DAPT effectiveness. Here, we have investigated this idea using platelets taken from healthy volunteers treated with anti-platelet drugs.
The balance between vascular prostacyclin, which is antithrombotic, and platelet thromboxane A