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One or more keywords matched the following properties of Smyth, Susan

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overview Inflammation and Thrombosis Program Drawing on a long-standing interest in platelet biology, our group has established animal models for studying the role of platelet membrane proteins in thrombosis and the response to arterial injury, and has delineated specific signaling systems responsible for mediating platelet-leukocyte interactions and for inflammation in the context of arterial injury and cardiac hypertrophy. We are interested in understanding the functional interplay between thrombosis and inflammation. Our work has resulted in observations about beneficial effects of antiplatelet drugs in infectious and inflammatory states of pneumonia and sepsis. This work has also spawned clinical trials of the effects of antithrombotic therapy on inflammation and the identification of biomarkers of ischemic heart disease. Current funded work continues to identify novel signaling pathways in platelets, which likely will be the target for future translational studies. Lysolipid Signaling Program Our group also has a longstanding research interest in the role of bioactive lysophospholipid, such as lysophosphatidic acid (LPA), as mediators of cardiovascular disease. The lysophospholipase D autotaxin (ATX) catalyzes the hydrolysis of circulating or cell-associated lysophosphatidylcholine (LPC) to generate LPA, which has potent, receptor-mediated effects on blood and vascular cells. LPA is a proteotypic member of a family of bioactive lipid phosphoric acids that function as receptor-active mediators with roles in cell growth, differentiation, apoptosis and development. Our contributions to the literature includes characterizing pathways for production and metabolism of LPA in the circulation; providing the first evidence of a pathologic role for LPA receptors in the response to arterial injury; identifying key structural and functional elements of ATX and mechanisms for regulation of ATX function by localization along cell surfaces; demonstrating roles for specific LPA receptors in experimental atherosclerosis. Current work is focused on identifying mechanistic links between dietary intake of lipids and cardiovascular disease risk. Current investigations are exploring the possibility that choline-containing lipids and adipose-derived ATX serve as links between diet and cardiovascular disease risk. LPA can hydrolyzed and inactivated by lipid phosphate phosphatase (LPP) enzymes present on cell membranes. A genome-wide association studies (GWAS) identified the PLPP3/PPAP2B gene encoding LPP3 as a novel loci associated with coronary artery disease susceptibility. We have established that LPP3 expression in mice is critical to attenuate inflammation, reduce smooth muscle cell proliferation, and maintain endothelial barrier function following vascular injury in an LPA-dependent manner. We have functionally validated that changes in LPP3 expression accelerates experimental atherosclerosis. Current studies are focused on understanding how heritable human variation in PLPP3 predisposes to the development of atherosclerosis and calcific aortic valve disease, which should translate identification of novel pathways for disease prevention.

One or more keywords matched the following items that are connected to Smyth, Susan

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Concept Platelet Aggregation Inhibitors
Academic Article The P2Y(12) antagonists, 2MeSAMP and cangrelor, inhibit platelet activation through P2Y(12)/G(i)-dependent mechanism.
Academic Article Cangrelor in addition to standard therapy reduces cardiac damage and inflammatory markers in patients with ST-segment elevation myocardial infarction.
Academic Article CYP2C19 Genotyping to Guide Antiplatelet Therapy After Percutaneous Coronary Interventions: One Size Rarely Fits All.
Academic Article Translational Implications of Platelets as Vascular First Responders.
Academic Article Obesity and Antiplatelets-Does One Size Fit All?
Academic Article Phosphodiesterase type 4 blockade prevents platelet-mediated neutrophil recruitment at the site of vascular injury.
Academic Article Antiplatelet therapy in prevention of cardio- and venous thromboembolic events.
Academic Article Integrin aIIbß3: from discovery to efficacious therapeutic target.
Academic Article Clopidogrel treatment and the incidence and severity of community acquired pneumonia in a cohort study and meta-analysis of antiplatelet therapy in pneumonia and critical illness.
Academic Article Preventing platelet thrombosis with a PAR1 pepducin.
Academic Article Platelet biology and response to antiplatelet therapy in women: implications for the development and use of antiplatelet pharmacotherapies for cardiovascular disease.
Academic Article Anti-platelet therapy.
Academic Article The case against routine aspirin use for primary prevention in low-risk adults.
Academic Article Genetic regulation of platelet receptor expression and function: application in clinical practice and drug development.
Academic Article Platelets unplugged: an ATVB special series focused on platelet biology.
Academic Article Bridging the gap between clinical trials of antiplatelet therapies and applications among elderly patients.
Academic Article Considerable variability in platelet activity among patients with coronary artery disease in response to an increased maintenance dose of clopidogrel.
Academic Article Thrombosis and antithrombotic therapy in women.
Academic Article Platelet function analysis: at the edge of meaning.
Academic Article G-protein-coupled receptors as signaling targets for antiplatelet therapy.
Academic Article Platelet activation and its patient-specific consequences.
Academic Article Aspirin resistance in patients with stable coronary artery disease with and without a history of myocardial infarction.
Academic Article A case report of simultaneous thrombosis of two coronary artery stents in association with clopidogrel resistance.
Academic Article Effects of abciximab on the acute pathology of blood vessels after arterial stenting in nonhuman primates.
Academic Article The evolution of platelet-directed pharmacotherapy.
Academic Article Aspirin dose for the prevention of cardiovascular disease: a systematic review.

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