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1. Platelet and Monocyte Activation After Transcatheter Aortic Valve Replacement (POTENT-TAVR): A Mechanistic Randomized Trial of Ticagrelor Versus Clopidogrel

Author

Zidar, David A., Al-Kindi, Sadeer, Longenecker, Chris T., Parikh, Sahil A., Gillombardo, Carl B., Funderburg, Nicholas T., Juchnowski, Steven, Huntington, Lauren, Jenkins, Trevor, Nmai, Christopher, Osnard, Michael, Shishebhor, Mehdi, Filby, Steven, Tatsuoka, Curtis, Lederman, Michael M., Blackstone, Eugene, Attizzani, Guilherme, and Simon, Daniel I.

Published
2023
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3. Coronary Stenting in High Bleeding Risk Patients With Small Coronary Arteries Followed by One-Month Dual Antiplatelet Therapy: Onyx ONE Clear

Author

Moreno, Raúl, Kandzari, David E., Kirtane, Ajay J., Windecker, Stephan, Latib, Azeem, Kedhi, Elvin, Mehran, Roxana, Price, Matthew J., Simon, Daniel I., Worthley, Stephen G., Spriggs, Douglas, Tolleson, Thaddeus, Nazif, Tamim, Golwala, Harsh, Kander, Nathan H., Liew, Houng B., Sardella, Gennaro, Tamburino, Corrado, Lung, Te-Hsin, Mahoney, Cecile, and Stone, Gregg W.

Published
2022
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4. Patients With Diabetes at High Bleeding Risk With 1-Month Dual Antiplatelet Therapy: Onyx ONE Clear Results

Author

Kedhi, Elvin, Windecker, Stephan, Latib, Azeem, Kirtane, Ajay J., Kandzari, David, Mehran, Roxana, Price, Matthew J., Abizaid, Alexandre, Simon, Daniel I., Zaman, Azfar, Fabbiocchini, Franco, Tie, Charlies, van ‘t Hof, Arnoud, de la Torre Hernandez, Jose M., Hammett, Christopher J., McLaurin, Brent, Potluri, Srinivasa, Smith, Timothy, Waksman, Ron, Ragosta, Michael, Parke, Maria, Lung, Te-Hsin, and Stone, Gregg W.

Published
2022
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5. Delivery of thrombolytic therapy using rod-shaped plant viral nanoparticles decreases the risk of hemorrhage

Author

Pitek, Andrzej S, Park, Jooneon, Wang, Yunmei, Gao, Huiyun, Hu, He, Simon, Daniel I, and Steinmetz, Nicole F

Subjects
Cardiovascular, Nanotechnology, Brain Disorders, Biotechnology, Bioengineering, Stroke, Heart Disease, Heart Disease - Coronary Heart Disease, Hematology, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Blood, Good Health and Well Being, Animals, Drug Delivery Systems, Fibrinolytic Agents, Hemorrhage, Mice, Mice, Inbred C57BL, Nanoparticles, Plant Viruses, Thrombolytic Therapy, Tissue Plasminogen Activator, Tobacco, Physical Sciences, Chemical Sciences, Technology, Nanoscience & Nanotechnology
Abstract

Cardiovascular thrombotic disease is an underlying cause of stroke, myocardial infarction and pulmonary embolism - some of the leading causes of death worldwide. Reperfusion therapy with anticoagulant, antiplatelet, and fibrinolytic agents has significantly reduced early mortality and morbidity from acute myocardial infarction and stroke. Nevertheless, bleeding side effects (e.g., intracranial hemorrhage) associated with the anti-thrombotic therapy can offset its benefits and limit its applicability to strictly defined short therapeutic windows. We have previously shown that elongated plant virus based nanoparticles can target cardiovascular thrombi and exhibited their utility for the delivery of streptokinase in an ex vivo model of thrombosis. Herein, we build upon our previous findings and demonstrate plant viral delivery of the current standard-of-care tissue plasminogen activator (tPA). Studies on a pre-clinical mouse model of arterial thrombosis indicate that while the therapeutic efficacy of free tPA and tPA-conjugated TMV are similar, the safety profile of the tPA-TMV formulation is improved, i.e. administration of the latter has less impact on hemostasis as demonstrated by decreased bleeding time. Thus, our data suggest that TMV-based delivery of thrombolytic therapies could be a promising and safer alternative to reperfusion therapy with the tPA.

Published
2018

6. Hospitalization for Heart Failure in the United States, UK, Taiwan, and Japan: An International Comparison of Administrative Health Records on 413,385 Individual Patients

Author

Sundaram, VARUN, NAGAI, TOSHIYUKI, CHIANG, CHERN-EN, REDDY, YOGESH N.V., CHAO, TZE-FAN, ZAKERI, ROSITA, BLOOM, CHLOE, NAKAI, MICHIKAZU, NISHIMURA, KUNIHIRO, HUNG, CHUNG-LIEH, MIYAMOTO, YOSHIHIRO, YASUDA, SATOSHI, BANERJEE, AMITAVA, ANZAI, TOSHIHISA, SIMON, DANIEL I., RAJAGOPALAN, SANJAY, CLELAND, JOHN G.F., SAHADEVAN, JAYAKUMAR, and QUINT, JENNIFER K.

Published
2022
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13. Assessment of Coronary Artery Calcium Using Dual-Energy Subtraction Digital Radiography

Author

Mafi, John N, Fei, Baowei, Roble, Sharon, Dota, Anthony, Katrapati, Prashanth, Bezerra, Hiram G, Wang, Hesheng, Wang, Wei, Ciancibello, Leslie, Costa, Marco, Simon, Daniel I, Orringer, Carl E, and Gilkeson, Robert C

Subjects
Cardiovascular, Biomedical Imaging, Prevention, Clinical Research, Heart Disease - Coronary Heart Disease, Heart Disease, Clinical Trials and Supportive Activities, Atherosclerosis, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, 4.2 Evaluation of markers and technologies, Good Health and Well Being, Angiography, Digital Subtraction, Calcinosis, Case-Control Studies, Coronary Angiography, Coronary Artery Disease, Feasibility Studies, Female, Humans, Male, Middle Aged, Pilot Projects, Reproducibility of Results, Retrospective Studies, Sensitivity and Specificity, Severity of Illness Index, Statistics, Nonparametric, Calcification detection, Cardiac imaging, Chest CT, Chest radiographs, Computed tomography, Coronary arteries, Coronary calcifications, Coronary disease, Digital radiography, Digital subtraction radiography, Dual-energy subtraction, Radiography, Dual-energy scanned projection, ROC-based analysis, Clinical Sciences, Nuclear Medicine & Medical Imaging
Abstract

Cardiovascular disease is the leading cause of global mortality, yet its early detection remains a vexing problem of modern medicine. Although the computed tomography (CT) calcium score predicts cardiovascular risk, relatively high cost ($250-400) and radiation dose (1-3 mSv) limit its universal utility as a screening tool. Dual-energy digital subtraction radiography (DE;

Published
2012

16. One-Month Dual Antiplatelet Therapy Following Percutaneous Coronary Intervention With Zotarolimus-Eluting Stents in High-Bleeding-Risk Patients

Author

Kandzari, David E., Kirtane, Ajay J., Windecker, Stephan, Latib, Azeem, Kedhi, Elvin, Mehran, Roxana, Price, Matthew J., Abizaid, Alexandre, Simon, Daniel I., Worthley, Stephen G., Zaman, Azfar, Choi, James W., Caputo, Ronald, Kanitkar, Mihir, McLaurin, Brent, Potluri, Srinivasa, Smith, Timothy, Spriggs, Douglas, Tolleson, Thaddeus, Nazif, Tamim, Parke, Maria, Lee, Lilian C., Lung, Te-Hsin, and Stone, Gregg W.

Published
2020
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17. First-in-Human Evaluation of a Novel Polymer-Free Drug-Filled Stent: Angiographic, IVUS, OCT, and Clinical Outcomes From the RevElution Study

Author

Worthley, Stephen, Shetty, Sharad, Sinhal, Ajay, Meredith, Ian, Abizaid, Alexandre, Jepson, Nigel, Bhindi, Ravinay, Lim, Soo Teik, Stewart, Peter, Barlis, Peter, Walters, Darren, Muller, David, Cox, Stephen, Bhagwandeen, Rohan, Worthley, Stephen G., Kirtane, Ajay J., Simon, Daniel I., Windecker, Stephan, Brar, Sandeep, Meredith, Ian T., Almonacid, Alexandra Popma, Chamié, Daniel, Maehara, Akiko, and Stone, Gregg W.

Published
2017
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19. Revascularization in ischaemic heart failure with preserved ejection fraction: a nationwide cohort study

Author

Deo, Salil V., Reddy, Yogesh N.V., Zakeri, Rosita, Karnib, Mohamad, Selvaganesan, Padmini, Elgudin, Yakov, Kilic, Ahmet, Rubelowsky, Joseph, Altarabsheh, Salah E., Osman, Mohammed N., Josephson, Richard A., Mohan, Sri Krishna Madan, Cmolik, Brian, Simon, Daniel I., Rajagopalan, Sanjay, Cleland, John G.F., Sahadevan, Jayakumar, and Sundaram, Varun

Subjects
Cohort Studies, Heart Failure, Risk Factors, Myocardial Infarction, Humans, Stroke Volume, Coronary Artery Disease, Prognosis, Cardiology and Cardiovascular Medicine, R1
Abstract

Aims: \ud Despite the common occurrence of coronary artery disease (CAD) and heart failure (HF) with preserved ejection fraction (HFpEF), there is limited evidence to guide revascularization.\ud \ud Methods and Results: \ud We investigated the long-term outcomes of coronary artery bypass grafting (CABG) in patients with HF and significant CAD across the spectrum of ejection fraction, using a large national cohort of patients from the Veteran Affairs (VA) Medical Centers in the US. Patients with HF were stratified into groups, HFpEF, HF with mid-range ejection fraction (HFmrEF), and HF with reduced ejection fraction (HFrEF) and compared to patients with no preoperative HF. We analysed 10 396 patients. Despite an increased hazard in the first year following revascularization, the long-term survival (median follow-up 6.6 years; interquartile range 3.7–10.1) of HFpEF post-CABG was similar to controls (hazard ratio 0.85, 95% confidence interval 0.68-1.06), but survival progressively declined with HFmrEF and HFrEF. Similar trends were seen with recurrent HF hospitalization with lower risk with baseline HFpEF (43.9 ± 6.9/100 patient-years) compared to HFmrEF (65.9 ± 3.8/100 patient-years) and HFrEF (93.4 ± 4.8/100 patient-years). Although HFpEF patients had lower mortality and HF hospitalization post-CABG compared to patients with a lower ejection fraction, they experienced the highest rates of future myocardial infarction.\ud \ud Conclusion: \ud Although HFpEF patients with CAD have greater short-term risk post-CABG, their long-term survival is comparable to controls. However, they are at increased risk for HF hospitalizations and myocardial infarction. These data support the safety of CABG in HFpEF patients and suggest continuum of mortality risk for ischaemic HF when stratified by baseline ejection fraction before revascularization.

Published
2022

22. Comparison of Outcomes of Transfemoral Transcatheter Aortic Valve Implantation Using a Minimally Invasive Versus Conventional Strategy

Author

Attizzani, Guilherme F., Alkhalil, Ahmad, Padaliya, Bimal, Tam, Chor-Cheung, Lopes, Joao Pedro, Fares, Anas, Bezerra, Hiram G., Medallion, Benjamin, Park, Soon, Deo, Salil, Sareyyupoglu, Basar, Parikh, Sahil, Zidar, David, Elgudin, Yakov, Popovich, Kehllee, Davis, Angela, Staunton, Elizabeth, Tomic, Ana, Mazzurco, Stacey, Avery, Edward, Markowitz, Alan, Simon, Daniel I., and Costa, Marco A.

Published
2015
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23. Stent Thrombosis in Drug-Eluting or Bare-Metal Stents in Patients Receiving Dual Antiplatelet Therapy

Author

Kereiakes, Dean J., Yeh, Robert W., Massaro, Joseph M., Driscoll-Shempp, Priscilla, Cutlip, Donald E., Steg, P. Gabriel, Gershlick, Anthony H., Darius, Harald, Meredith, Ian T., Ormiston, John, Tanguay, Jean-François, Windecker, Stephan, Garratt, Kirk N., Kandzari, David E., Lee, David P., Simon, Daniel I., Iancu, Adrian Corneliu, Trebacz, Jaroslaw, and Mauri, Laura

Published
2015
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27. Clinical Outcomes of PCI With a Zotarolimus-Eluting Stent Followed by One-Month DAPT in High-Bleeding-Risk Patients With Small (≤2.5 mm) Coronary Arteries: One-Year Analysis From the Onyx ONE Clear Study

Author

Moreno, Raul, primary, Kandzari, David, additional, Kirtane, Ajay, additional, Windecker, Stephan, additional, Latib, Azeem, additional, Kedhi, Elvin, additional, Mehran, Roxana, additional, Price, Mathew J., additional, Simon, Daniel I., additional, Worthley, Stephen G., additional, Lung, Te-Hsin, additional, Mahoney, Cecile, additional, and Stone, Gregg W., additional

Published
2022
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29. Polymer-Based Versus Polymer-Free Stents in High Bleeding Risk Patients

Author

Windecker, Stephan, primary, Latib, Azeem, additional, Kedhi, Elvin, additional, Kirtane, Ajay J., additional, Kandzari, David E., additional, Mehran, Roxana, additional, Price, Matthew J., additional, Abizaid, Alexandre, additional, Simon, Daniel I., additional, Worthley, Stephen G., additional, Zaman, Azfar, additional, Hudec, Martin, additional, Poliacikova, Petra, additional, Kahar bin Abdul Ghapar, Abdul, additional, Selvaraj, Kamaraj, additional, Petrov, Ivo, additional, Mylotte, Darren, additional, Pinar, Eduardo, additional, Moreno, Raul, additional, Fabbiocchi, Franco, additional, Pasupati, Sanjeevan, additional, Kim, Hyo-Soo, additional, Aminian, Adel, additional, Tie, Charles, additional, Wlodarczak, Adrian, additional, Hur, Seung-Ho, additional, Marx, Steven O., additional, Ali, Ziad A., additional, Parke, Maria, additional, Lung, Te-Hsin, additional, and Stone, Gregg W., additional

Published
2022
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31. Rheumatic Heart Disease Treatment Cascade in Uganda

Author

Longenecker, Chris T., Morris, Stephen R., Aliku, Twalib O., Beaton, Andrea, Costa, Marco A., Kamya, Moses R., Kityo, Cissy, Lwabi, Peter, Mirembe, Grace, Nampijja, Dorah, Rwebembera, Joselyn, Sable, Craig, Salata, Robert A., Scheel, Amy, Simon, Daniel I., Ssinabulya, Isaac, and Okello, Emmy

Published
2017
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32. Hospitalization for heart failure in the USA, UK, Taiwan and Japan: an international comparison of administrative health records on 417,385 individual patients

Author

Sundaram, Varun, Nagai, Toshiyuki, Chiang, Chern-En, Reddy, Yogesh N.V., Chao, Tze-Fan, Zakeri, Rosita, Bloom, Chloe, Nakai, Michikazu, Nishimura, Kunihiro, Hung, Chung-Lieh, Miyamoto, Yoshihiro, Yasuda, Satoshi, Banerjee, Amitava, Anzai, Toshihisa, Simon, Daniel I., Rajagopalan, Sanjay, Cleland, John G.F., Sahadevan, Jayakumar, and Quint, Jennifer K.

Abstract

Background\ud : Registries show international variations in the characteristics and outcome of patients with heart failure (HF) but national samples are rarely large, and case-selection may be biased due to enrolment in academic centres. National administrative datasets provide large samples with a low risk of bias. In this study, we compared the characteristics, healthcare resource utilization (HRU) and outcomes of patients with primary HF hospitalizations (HFH) using electronic health records (EHR) from four high-income countries (USA, UK, Taiwan, Japan) on three continents.\ud \ud Methods and Results\ud : We used EHR to identify unplanned HFH between 2012-2014. We identified 231,512, 10,991, 36,900 and 133,982 patients with a primary HFH from USA, UK, Taiwan and Japan, respectively. HFH per 100,000 population was highest in USA and lowest in Taiwan. Patients in Taiwan and Japan were older but fewer were obese or had chronic kidney disease. LOHS was shortest in USA (median 4 days) and longer in UK, Taiwan and Japan (medians 7, 9 and 17 days, respectively). HRU during hospitalization was highest in Japan and lowest in UK. Crude and direct standardized in-hospital mortality was lowest in USA (direct standardized rates: 1.8 [95%CI:1.7-1.9]%)and progressively higher in Taiwan (direct standardized rates: 3.9 [95%CI:3.8-4.1]%), UK (direct standardized rates: 6.4 [95%CI:6.1-6.7]%) and Japan (direct standardized rates: 6.7 [95%CI:6.6-6.8]%). 30-day all-cause (25.8%) and HF (7.2%) readmissions were highest in USA and lowest in Japan (11.9% and 5.1% respectively).\ud \ud Conclusion\ud : Marked international variations in patient characteristics, HRU and clinical outcome exist; understanding them might inform health care policy and international trial design.

Published
2022

34. A-13 | One Month DAPT in High Bleeding Risk ACS Patients: 2-year Subgroup Analysis from Onyx ONE Clear

Author

Kandzari, David E., primary, Kirtane, Ajay J., additional, Mehran, Roxana, additional, Price, Matthew J., additional, Simon, Daniel I., additional, Kedhi, Elvin, additional, Latib, Azeem, additional, Abizaid, Alexandre, additional, Worthley, Stephen, additional, Zaman, Azfar, additional, Parke, Maria, additional, Lung, Te-Hsin, additional, Windecker, Stephan, additional, and Stone, Gregg W., additional

Published
2022
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35. Activated Platelets Upregulate β2 Integrin Mac-1 (CD11b/CD18) on Dendritic Cells, Which Mediates Heterotypic Cell–Cell Interaction

Author

Nording, Henry, primary, Sauter, Manuela, additional, Lin, Chaolan, additional, Steubing, Rebecca, additional, Geisler, Sven, additional, Sun, Ying, additional, Niethammer, Joel, additional, Emschermann, Fréderic, additional, Wang, Yunmei, additional, Zieger, Barbara, additional, Nieswandt, Bernhard, additional, Kleinschnitz, Christoph, additional, Simon, Daniel I., additional, and Langer, Harald F., additional

Published
2022
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41. CRT-100.52 Clinical Outcomes of PCI With a Zotarolimus-Eluting Stent Followed by One-Month DAPT in High-Bleeding-Risk Patients With Small (≤2.5 mm) Coronary Arteries: One-Year Analysis From the Onyx ONE Clear Study

Author

Moreno, Raul, primary, Kandzari, David, additional, Kirtane, Ajay, additional, Windecker, Stephan, additional, Latib, Azeem, additional, Kedhi, Elvin, additional, Mehran, Roxana, additional, Price, Mathew J., additional, Simon, Daniel I., additional, Worthley, Stephen G., additional, Lung, Te-Hsin, additional, Mahoney, Cecile, additional, and Stone, Gregg W., additional

Published
2022
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42. Polymer-Based Versus Polymer-Free Stents in High Bleeding Risk Patients: Final 2-Year Results From Onyx ONE

Author

Windecker, Stephan, Latib, Azeem, Kedhi, Elvin, Kirtane, Ajay J, Kandzari, David E, Mehran, Roxana, Price, Matthew J, Abizaid, Alexandre, Simon, Daniel I, Worthley, Stephen G, Zaman, Azfar, Hudec, Martin, Poliacikova, Petra, Kahar Bin Abdul Ghapar, Abdul, Selvaraj, Kamaraj, Petrov, Ivo, Mylotte, Darren, Pinar, Eduardo, Moreno, Raul, Fabbiocchi, Franco, Pasupati, Sanjeevan, Kim, Hyo-Soo, Aminian, Adel, Tie, Charles, Wlodarczak, Adrian, Hur, Seung-Ho, Marx, Steven O, Ali, Ziad A, Parke, Maria, Lung, Te-Hsin, and Stone, Gregg W

Subjects
Percutaneous Coronary Intervention, Treatment Outcome, Polymers, Humans, Drug-Eluting Stents, Hemorrhage, Stents, 610 Medicine & health, Prosthesis Design, Platelet Aggregation Inhibitors
Abstract

BACKGROUND Resolute Onyx polymer-based zotarolimus-eluting stents (ZES) were noninferior in safety and effectiveness to BioFreedom polymer-free biolimus A9-coated stents (DCS) in high-bleeding-risk (HBR) patients treated with 1-month dual antiplatelet therapy (DAPT) followed by single antiplatelet therapy (SAPT) at 1 year. OBJECTIVES This study reports the final 2-year results of the randomized Onyx ONE trial. METHODS The Onyx ONE (A Randomized Controlled Trial With Resolute Onyx in One Month Dual Antiplatelet Therapy (DAPT) for High-Bleeding Risk Patients) trial randomly assigned HBR patients to treatment with ZES or DCS. Following 1-month DAPT, event-free patients received SAPT (either aspirin or a P2Y12 inhibitor at physician discretion). The primary safety endpoint, a composite of cardiac death, myocardial infarction, or stent thrombosis at 1 year, was determined at 1 year. Rates of primary and secondary endpoints were calculated after final follow-up at 2 years. RESULTS A total of 1,003 patients were randomly allocated to ZES and 993 patients to DCS. Follow-up was complete in 980 (97.7%) ZES patients and 962 (96.9%) DCS patients at 2 years. The primary safety endpoint occurred in 208 (21.2%) patients in the ZES group and 199 (20.7%) patients in the DCS group (risk difference: 0.5%; 95% CI: -3.1% to 4.2%; P = 0.78) at 2 years without significant differences in individual components of the composite endpoint. The secondary effectiveness endpoint occurred in 217 (22.1%) patients in the ZES group and 202 (21.0%) patients in the DCS group (risk difference: 1.1%; 95% CI: -2.5% to 4.8%; P = 0.54). CONCLUSIONS Among patients at HBR treated with 1-month DAPT followed by SAPT, the Resolute Onyx polymer-based ZES had similar 2-year outcomes for the primary safety and secondary effectiveness endpoint compared with the BioFreedom polymer-free DCS. (A Randomized Controlled Trial With Resolute Onyx in One Month Dual Antiplatelet Therapy [DAPT] for High-Bleeding Risk Patients [Onyx ONE]; NCT03344653).

Published
2021

43. Critical role for Syk in responses to vascular injury

Author

Andre, Patrick, Morooka, Toshifumi, Sim, Derek, Abe, Keith, Lowell, Clifford, Nanda, Nisha, Delaney, Suzanne, Siu, Gail, Yan, Yibing, Hollenbach, Stan, Pandey, Anjali, Gao, Huiyun, Wang, Yunmei, Nakajima, Kohsuke, Parikh, Sahil A., Shi, Can, Phillips, David, Owen, Whyte, Sinha, Uma, and Simon, Daniel I.

Published
2011
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46. Clinical outcomes according to lesion complexity in high bleeding risk patients treated with 1‐month dual antiplatelet therapy following PCI: Analysis from the Onyx ONE clear study

Author

Kandzari, David E., primary, Kirtane, Ajay J., additional, Mehran, Roxana, additional, Price, Matthew J., additional, Simon, Daniel I., additional, Latib, Azeem, additional, Kedhi, Elvin, additional, Abizaid, Alexandre, additional, Worthley, Stephen G., additional, Zaman, Azfar, additional, Hudec, Martin, additional, Stoler, Robert, additional, Choi, James W., additional, Kanitkar, Mihir, additional, Conradie, Andre, additional, Tam, Chor‐Cheung Frankie, additional, Walton, Antony, additional, Gruberg, Luis, additional, Ando, Kenji, additional, Lee, Lilian C., additional, Lung, Te‐Hsin, additional, Windecker, Stephan, additional, and Stone, Gregg W., additional

Published
2021
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47. Platelet-derived S100 family member myeloid-related protein-14 regulates thrombosis

Author

Wang, Yunmei, Fang, Chao, Gao, Huiyun, Bilodeau, Matthew L., Zhang, Zijie, Croce, Kevin, Liu, Shijian, Morooka, Toshifumi, Sakuma, Masashi, Nakajima, Kohsuke, Yoneda, Shuichi, Shi, Can, Zidar, David, Andre, Patrick, Stephens, Gillian, Silverstein, Roy L., Hogg, Nancy, Schmaier, Alvin H., and Simon, Daniel I.

Subjects
Binding proteins -- Properties, Blood clot -- Development and progression, Hemostasis -- Research, Physiological research, Thrombosis -- Development and progression, Health care industry
Abstract

Expression of the gene encoding the S100 calcium-modulated protein family member MRP-14 (also known as S100A9) is elevated in platelets from patients presenting with acute myocardial infarction (MI) compared with those from patients with stable coronary artery disease; however, a causal role for MRP-14 in acute coronary syndromes has not been established. Here, using multiple models of vascular injury, we found that time to arterial thrombotic occlusion was markedly prolonged in [Mrp14.sup.-/-] mice. We observed that MRP-14 and MRP-8/ MRP-14 heterodimers (S100A8/A9) are expressed in and secreted by platelets from WT mice and that thrombus formation was reduced in whole blood from [Mrp14.sup.-/-] mice. Infusion of WT platelets, purified MRP-14, or purified MRP-8/MRP-14 heterodimers into [Mrp14.sup.-/-] mice decreased the time to carotid artery occlusion after injury, indicating that platelet-derived MRP-14 directly regulates thrombosis. In contrast, infusion of purified MRP-14 into mice deficient for both MRP-14 and CD36 failed to reduce carotid occlusion times, indicating that CD36 is required for MRP-14-dependent thrombosis. Our data identify a molecular pathway of thrombosis that involves platelet MRP-14 and CD36 and suggest that targeting MRP-14 has potential for treating atherothrombotic disorders, including MI and stroke., Introduction Acute myocardial infarction (MI) commonly results from the atherosclerotic plaque disruption (1) and thrombosis that cause coronary artery occlusion (2). Angioscopic (3) and pathological (1) observations indicate that platelets [...]

Published
2014
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48. Kruppel-like factor 15 is critical for vascular inflammation

Author

Lu, Yuan, Zhang, Lisheng, Liao, Xudong, Sangwung, Panjamaporn, Prosdocimo, Domenick A., Zhou, Guangjin, Votruba, Alexander R., Brian, Leigh, Han, Yuh Jung, Gao, Huiyun, Wang, Yunmei, Shimizu, Koichi, Weinert-Stein, Kaitlyn, Khrestian, Maria, Simon, Daniel I., Freedman, Neil J., and Jain, Mukesh K.

Subjects
Inflammation -- Research, Smooth muscle -- Physiological aspects, Blood circulation disorders -- Research, Health care industry
Abstract

Activation of cells intrinsic to the vessel wall is central to the initiation and progression of vascular inflammation. As the dominant cellular constituent of the vessel wall, vascular smooth muscle [...]

Published
2013
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