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938 results on '"Maron, Bradley A."'

9. Diagnosis and Treatment of Right Heart Failure in Pulmonary Vascular Diseases: A National Heart, Lung, and Blood Institute Workshop.

Author

Leopold, Jane A, Kawut, Steven M, Aldred, Micheala A, Archer, Stephen L, Benza, Ray L, Bristow, Michael R, Brittain, Evan L, Chesler, Naomi, DeMan, Frances S, Erzurum, Serpil C, Gladwin, Mark T, Hassoun, Paul M, Hemnes, Anna R, Lahm, Tim, Lima, Joao AC, Loscalzo, Joseph, Maron, Bradley A, Rosa, Laura Mercer, Newman, John H, Redline, Susan, Rich, Stuart, Rischard, Franz, Sugeng, Lissa, Tang, WH Wilson, Tedford, Ryan J, Tsai, Emily J, Ventetuolo, Corey E, Zhou, YouYang, Aggarwal, Neil R, and Xiao, Lei

Subjects
Humans, Hypertension, Pulmonary, Ventricular Dysfunction, Right, Pulmonary Circulation, Ventricular Function, Right, United States, Heart Failure, National Heart, Lung, and Blood Institute (U.S.), Hematology, Rare Diseases, Heart Disease, Lung, Cardiovascular, Respiratory, Good Health and Well Being, cardiovascular disease, hemodynamics, morbidity, prognosis, vascular diseases, Biochemistry and Cell Biology, Cardiorespiratory Medicine and Haematology, Medical Physiology, Cardiovascular System & Hematology
Abstract

Right ventricular dysfunction is a hallmark of advanced pulmonary vascular, lung parenchymal, and left heart disease, yet the underlying mechanisms that govern (mal)adaptation remain incompletely characterized. Owing to the knowledge gaps in our understanding of the right ventricle (RV) in health and disease, the National Heart, Lung, and Blood Institute (NHLBI) commissioned a working group to identify current challenges in the field. These included a need to define and standardize normal RV structure and function in populations; access to RV tissue for research purposes and the development of complex experimental platforms that recapitulate the in vivo environment; and the advancement of imaging and invasive methodologies to study the RV within basic, translational, and clinical research programs. Specific recommendations were provided, including a call to incorporate precision medicine and innovations in prognosis, diagnosis, and novel RV therapeutics for patients with pulmonary vascular disease.

Published
2021

12. Recent Advances in Systems and Network Medicine: Meeting Report from the First International Conference in Systems and Network Medicine

Author

Kurnat-Thoma, Emma, Baranova, Ancha, Baird, Pat, Brodsky, Elia, Butte, Atul J, Cheema, Amrita K, Cheng, Feixiong, Dutta, Shuchismita, Grant, Christina, Giordano, James, Maitland-van der Zee, Anke H, Fridsma, Douglas B, Jarrin, Robert, Kann, Maricel G, Keeney, Jonathon, Loscalzo, Joseph, Madhavan, Guru, Maron, Bradley A, McBride, Dennis K, McKean, Maeve, Mun, Seong K, Palmer, James C, Patel, Bakul, Parakh, Kapil, Pariser, Anne R, Pristipino, Christian, Radstake, Timothy RDJ, Rajasimha, Harsha K, Rouse, William B, Rozman, Damjana, Saleh, Alif, Schmidt, Harald HHW, Schultz, Nikolaus, Sethi, Tavpritesh, Silverman, Edwin K, Skopac, Jessica, Svab, Igor, Trujillo, Sylvia, Valentine, James E, Verma, Dinesh, West, Bruce J, and Vasudevan, Sona

Subjects
Biomedical and Clinical Sciences, Philosophy and Religious Studies, History and Philosophy Of Specific Fields, Generic health relevance, Good Health and Well Being, artificial intelligence, big data, ethical legal social implications, international conference, network medicine, regulatory and health policy, systems
Abstract

The First International Conference in Systems and Network Medicine gathered together 200 global thought leaders, scientists, clinicians, academicians, industry and government experts, medical and graduate students, postdoctoral scholars and policymakers. Held at Georgetown University Conference Center in Washington D.C. on September 11-13, 2019, the event featured a day of pre-conference lectures and hands-on bioinformatic computational workshops followed by two days of deep and diverse scientific talks, panel discussions with eminent thought leaders, and scientific poster presentations. Topics ranged from: Systems and Network Medicine in Clinical Practice; the role of -omics technologies in Health Care; the role of Education and Ethics in Clinical Practice, Systems Thinking, and Rare Diseases; and the role of Artificial Intelligence in Medicine. The conference served as a unique nexus for interdisciplinary discovery and dialogue and fostered formation of new insights and possibilities for health care systems advances.

Published
2020

20. Clinical Characteristics and Transplant-Free Survival Across the Spectrum of Pulmonary Vascular Disease

Author

Hemnes, Anna R., Leopold, Jane A., Radeva, Milena K., Beck, Gerald J., Abidov, Aiden, Aldred, Micheala A., Barnard, John, Rosenzweig, Erika B., Borlaug, Barry A., Chung, Wendy K., Comhair, Suzy A.A., Desai, Ankit A., Dubrock, Hilary M., Erzurum, Serpil C., Finet, J. Emanuel, Frantz, Robert P., Garcia, Joe G.N., Geraci, Mark W., Gray, Michael P., Grunig, Gabriele, Hassoun, Paul M., Highland, Kristin B., Hill, Nicholas S., Hu, Bo, Kwon, Deborah H., Jacob, Miriam S., Jellis, Christine L., Larive, A. Brett, Lempel, Jason K., Maron, Bradley A., Mathai, Stephen C., McCarthy, Kevin, Mehra, Reena, Nawabit, Rawan, Newman, John H., Olman, Mitchell A., Park, Margaret M., Ramos, Jose A., Renapurkar, Rahul D., Rischard, Franz P., Sherer, Susan G., Tang, W.H. Wilson, Thomas, James D., Vanderpool, Rebecca R., Waxman, Aaron B., Wilcox, Jennifer D., Yuan, Jason X.-J., and Horn, Evelyn M.

Published
2022
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22. Clinical Response to Pulmonary Arterial Hypertension Treatment Does Not Depend on Pulmonary Arterial Wedge Pressure: A Meta-Analysis Using Individual Participant Data from Randomized Clinical Trials.

Author

Kovacs, Gabor, Moutchia, Jude, Zeder, Katarina, Maron, Bradley A., Al-Naamani, Nadine, Ventetuolo, Corey, Olschewski, Horst, and Kawut, Steven M.

Subjects
CLINICAL trials, PULMONARY arterial hypertension, CORONARY artery disease, PULMONARY hypertension, RANDOMIZED controlled trials
Abstract

This letter, published in the American Journal of Respiratory & Critical Care Medicine, presents the findings of a meta-analysis of individual participant data from randomized controlled trials (RCTs) on pulmonary arterial hypertension (PAH). The analysis aimed to determine if there is an interaction between baseline pulmonary arterial wedge pressure (PAWP) and treatment effects in terms of change in 6-minute-walk distance (6MWD) and time to clinical worsening (TTCW). The results showed no significant interaction between baseline PAWP and treatment effects, suggesting that the beneficial effects of PAH drugs are not dependent on the baseline PAWP value. However, it is important to note that the analysis only included patients enrolled in RCTs and may not be generalizable to all patients with PAH. Clinical decisions should be made based on a comprehensive evaluation of the patient's condition. [Extracted from the article]

Published
2024
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24. NEDD9 targets COL3A1 to promote endothelial fibrosis and pulmonary arterial hypertension

Author

Samokhin, Andriy O, Stephens, Thomas, Wertheim, Bradley M, Wang, Rui-Sheng, Vargas, Sara O, Yung, Lai-Ming, Cao, Minwei, Brown, Marcel, Arons, Elena, Dieffenbach, Paul B, Fewell, Jason G, Matar, Majed, Bowman, Frederick P, Haley, Kathleen J, Alba, George A, Marino, Stefano M, Kumar, Rahul, Rosas, Ivan O, Waxman, Aaron B, Oldham, William M, Khanna, Dinesh, Graham, Brian B, Seo, Sachiko, Gladyshev, Vadim N, Yu, Paul B, Fredenburgh, Laura E, Loscalzo, Joseph, Leopold, Jane A, and Maron, Bradley A

Subjects
Rare Diseases, Lung, 2.1 Biological and endogenous factors, Aetiology, Cardiovascular, Adaptor Proteins, Signal Transducing, Animals, Collagen Type III, Endothelial Cells, Female, Fibrosis, Humans, Hypertension, Pulmonary, Male, Phosphoproteins, Protein Binding, Pulmonary Artery, Rats, Rats, Sprague-Dawley, Smad3 Protein, Systems Biology, Biological Sciences, Medical and Health Sciences
Abstract

Germline mutations involving small mothers against decapentaplegic-transforming growth factor-β (SMAD-TGF-β) signaling are an important but rare cause of pulmonary arterial hypertension (PAH), which is a disease characterized, in part, by vascular fibrosis and hyperaldosteronism (ALDO). We developed and analyzed a fibrosis protein-protein network (fibrosome) in silico, which predicted that the SMAD3 target neural precursor cell expressed developmentally down-regulated 9 (NEDD9) is a critical ALDO-regulated node underpinning pathogenic vascular fibrosis. Bioinformatics and microscale thermophoresis demonstrated that oxidation of Cys18 in the SMAD3 docking region of NEDD9 impairs SMAD3-NEDD9 protein-protein interactions in vitro. This effect was reproduced by ALDO-induced oxidant stress in cultured human pulmonary artery endothelial cells (HPAECs), resulting in impaired NEDD9 proteolytic degradation, increased NEDD9 complex formation with Nk2 homeobox 5 (NKX2-5), and increased NKX2-5 binding to COL3A1 Up-regulation of NEDD9-dependent collagen III expression corresponded to changes in cell stiffness measured by atomic force microscopy. HPAEC-derived exosomal signaling targeted NEDD9 to increase collagen I/III expression in human pulmonary artery smooth muscle cells, identifying a second endothelial mechanism regulating vascular fibrosis. ALDO-NEDD9 signaling was not affected by treatment with a TGF-β ligand trap and, thus, was not contingent on TGF-β signaling. Colocalization of NEDD9 with collagen III in HPAECs was observed in fibrotic pulmonary arterioles from PAH patients. Furthermore, NEDD9 ablation or inhibition prevented fibrotic vascular remodeling and pulmonary hypertension in animal models of PAH in vivo. These data identify a critical TGF-β-independent posttranslational modification that impairs SMAD3-NEDD9 binding in HPAECs to modulate vascular fibrosis and promote PAH.

Published
2018

25. Lactate transport inhibition therapeutically reprograms fibroblast metabolism in experimental pulmonary fibrosis

Author

Ziehr, David R., primary, Li, Fei, additional, Parnell, K. Mark, additional, Krah, Nathan M., additional, Leahy, Kevin J., additional, Guillermier, Christelle, additional, Varon, Jack, additional, Baron, Rebecca M., additional, Maron, Bradley A., additional, Philp, Nancy J., additional, Hariri, Lida P., additional, Kim, Edy Yong, additional, Steinhauser, Matthew L., additional, Knipe, Rachel S., additional, Rutter, Jared, additional, and Oldham, William, additional

Published
2024
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32. The Management of Mild Pulmonary Hypertension in Clinical Practice.

Author

Zeder, Katarina, Brittain, Evan, Kovacs, Gabor, and Maron, Bradley A.

Subjects
PULMONARY hypertension, VASCULAR resistance, PULMONARY artery, CARDIAC catheterization, MEDICAL personnel
Abstract

The definition of pulmonary hypertension (PH) has been revised recently, with the mean pulmonary artery pressure (mPAP) threshold (assessed by right heart catheterization) reduced from ⩾25 mm Hg to >20 mm Hg. This change reflects the mPAP upper limit of normal and a lower limit that is independently associated with adverse outcomes. To improve the specificity of diagnosing pathogenic increases in mPAP, however, a diagnosis of precapillary PH now also includes pulmonary vascular resistance >2.0 Wood units (WU) (lowered from >3.0 WU). These changes are positioned to capture approximately 55% more patients with PH. Because all clinical trials showing a benefit of pulmonary vasodilator therapy in precapillary PH used the classical hemodynamic definition, the approach to the diagnosis and management of patients with mild PH (i.e., mPAP 21–24 mm Hg and pulmonary vascular resistance 2–3 WU) requires particular consideration. Here, we use a question/answer format to discuss key areas in the management of mild PH, including practical information tailored to clinicians without training in PH. [ABSTRACT FROM AUTHOR]

Published
2024
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36. Impact of the New Pulmonary Hypertension Definition on Heart Transplant Outcomes: Expanding the Hemodynamic Risk Profile

Author

Crawford, Todd C., Leary, Peter J., Fraser, Charles D., III, Suarez-Pierre, Alejandro, Magruder, J. Trent, Baumgartner, William A., Zehr, Kenton J., Whitman, Glenn J., Masri, S. Carolina, Sheikh, Farooq, De Marco, Teresa, Maron, Bradley A., Sharma, Kavita, Gilotra, Nisha A., Russell, Stuart D., Houston, Brian A., Ramu, Bhavadharini, and Tedford, Ryan J.

Published
2020
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40. Automated CT-Based Quantification of Pulmonary Veins Shows Greater Central Venous Dilation in Group 2 Pulmonary Hypertension Compared With Group 1 Pulmonary Arterial Hypertension and Control Subjects

Author

Synn, Andrew J., primary, Harder, Eileen M., additional, Nardelli, Pietro, additional, Ross, James C., additional, Maron, Bradley A., additional, Leopold, Jane A., additional, Waxman, Aaron B., additional, San José Estépar, Raúl, additional, Washko, George R., additional, and Rahaghi, Farbod N., additional

Published
2023
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41. Pulmonary hypertension in heart failure: the good, the bad, and the ugly.

Author

Rosenkranz, Stephan, Hoeper, Marius M, and Maron, Bradley A

Subjects
PULMONARY artery diseases, HEART valve diseases, CARDIO-renal syndrome, RIGHT ventricular dysfunction, CARDIAC patients, HEART failure
Abstract

The article discusses the impact of pulmonary hypertension (PH) on patients with heart failure (HF). PH is frequently seen in HF patients and is associated with increased mortality. The article highlights the updated definitions of PH and pre-capillary PH provided by the European Society of Cardiology (ESC) and European Respiratory Society (ERS) Guidelines. The study by Fauvel et al. demonstrates that the refined definitions of PH and pre-capillary PH are valid and that patients with values above the new thresholds are at increased risk of adverse outcomes. The article also mentions the need for further research on the prognostic implications and therapeutic options for PH in HF patients. [Extracted from the article]

Published
2024
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44. The application of big data to cardiovascular disease: paths to precision medicine

Author

Leopold, Jane A., Maron, Bradley A., and Loscalzo, Joseph

Subjects
Precision medicine, Clopidogrel, Big data, Cardiac patients -- Drug therapy, Cardiovascular diseases -- Genetic aspects -- Drug therapy, Clinical trials, Diseases, Health care industry
Abstract

Advanced phenotyping of cardiovascular diseases has evolved with the application of high-resolution omics screening to populations enrolled in large-scale observational and clinical trials. This strategy has revealed that considerable heterogeneity exists at the genotype, endophenotype, and clinical phenotype levels in cardiovascular diseases, a feature of the most common diseases that has not been elucidated by conventional reductionism. In this discussion, we address genomic context and (endo)phenotypic heterogeneity, and examine commonly encountered cardiovascular diseases to illustrate the genotypic underpinnings of (endo)phenotypic diversity. We highlight the existing challenges in cardiovascular disease genotyping and phenotyping that can be addressed by the integration of big data and interpreted using novel analytical methodologies (network analysis). Precision cardiovascular medicine will only be broadly applied to cardiovascular patients once this comprehensive data set is subjected to unique, integrative analytical strategies that accommodate molecular and clinical heterogeneity rather than ignore or reduce it., Introduction Parallel advances and increased ease of access to high-throughput next-generation genomic, metabolomic, transcriptomic, and proteomic arrays coupled with widespread adaptation of the electronic health record heralded the era of [...]

Published
2020
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