tbuckley/cabot-search huggingface dataset:
CLINICAL, LABORATORY, AND CORONARY ATHEROSCLEROTIC PREDICTORS OF NON-RESPONSE TO STATIN THERAPY: INSIGHTS FROM THE PROSPECTIVE, MULTICENTER, INTERNATIONAL PARADIGM SERIAL CCTA REGISTRY
Authors: Alexander van Rosendael, Inge van den Hoogen, Sang-Eun Lee, Daniele Andreini, Matthew Budoff, Filippo Cademartiri, Kavitha Chinnaiyan, Jung Hyun Choi, Eun Ju Chun, Ilan Gottlieb, Martin Hadamitzky, Yong-Jin Kim, Byoung Kwon Lee, Jonathon Leipsic, Hugo Marques, Gianluca Pontone, Sangshoon Shin, Jagat Narula, Daniel Berman, Leslee J. Shaw, Fay Lin, James Min, Hyuk-Jae Chang
Journal: Journal of the American College of Cardiology (2019)
CARDIAC REHABILITATION USE AMONG ELIGIBLE MEDICARE FEE-FOR-SERVICE BENEFICIARIES, 2016-2017
Authors: Matthew Ritchey, Sha Maresh, Steven Keteyian, Clinton Brawner, Alexis Beatty, Mary Whooley, Jessica McNeely, Thomas Shaffer, Sandra Jackson, Tiffany Chang, Haley Stolp, Janet Wright
Journal: Journal of the American College of Cardiology (2019)
PROGNOSTIC IMPACT OF GERIATRIC NUTRITIONAL RISK INDEX IN ELDERLY PATIENTS WITH HEART FAILURE
Authors: Takahiro Okano, Hirohiko Motoki, Masatoshi Minamisawa, Kazuhiro Kimura, Soichiro Ebisawa, Ayako Okada, Morio Shoda, Koichiro Kuwahara
Journal: Journal of the American College of Cardiology (2019)
MitraClip and Tertiary Mitral Regurgitation—Mitral Regurgitation Gets Curiouser and Curiouser
Authors: Blase A. Carabello
Journal: JAMA Cardiology (2019)

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Abstract 18115: Ranking Businesses and Municipal Locations by Spatiotemporal Cardiac Arrest Risk to Guide Public Defibrillator Placement
Authors: Christopher L Sun, Steven C Brooks, Laurie J Morrison, Timothy C Chan
Journal: Circulation (2016)

Background: Efforts to guide AED placement for out-of-hospital cardiac arrest (OHCA) treatment have focused on identifying broadly defined location types without considering hours of operation. Bro...
A New Simplified Prognostic Index Integrating the Type of Extra-Nodal Involvement and Age for Ann Arbor Stage IV Hodgkin Lymphoma Patients Diagnosed at TEP-Scanner Era: A Retrospective Analysis from Lymphoma Study Association (LYSA) Centers
Authors: Camille Golfier, Delphine Maucort-Boulch, Emmanuelle Nicolas-Virelizier, Cedric Rossi, Pierre Sesques, Nicolas Vantard, Bertrand Favier, Emmanuel Bachy, Florence Broussais-Guillaumot, Emmanuelle Ferrant, Dana Ghergus, Lionel Karlin, Anne Lazareth, Violaine Safar, Clementine Sarkozy, Souad Assaad, Laure Lebras, Philippe Rey, Jean-Noel Bastie, Alexandra Traverse-Glehen, Laurent Martin, Jeremie Tordo, Alina Berriolo-Riedinger, Gilles Salles, Rene-Olivier Casasnovas, Herve Ghesquieres
Journal: Blood (2018)
NATIONAL LANDSCAPE OF HOSPITALIZATIONS IN PATIENTS WITH LEFT VENTRICULAR ASSIST DEVICE: INSIGHTS FROM THE NATIONAL READMISSION DATABASE 2010-2015
Authors: Alejandro Lemor, Gabriel Hernandez, Waleed Al-Darzi, Youssef Nasr, Pedro Villablanca, Vanessa Blumer, Cristina Tita, Celeste T. Williams, Yelena Selektor, Jennifer Cowger
Journal: Journal of the American College of Cardiology (2019)
Abstract 311: <i>In vitro</i> Regulation of G-protein Coupled Receptor Kinase 5 (GRK5) Induced Cardiac Hypertrophy by a Novel Interaction With the Phosphatase PHLPP2
Authors: Szu-Tsen Yeh, Cristina Zambrano, Walter Koch, Nicole Purcell
Journal: Circulation Research (2018)

PHLPP is a Ser/Thr phosphatase that has been shown to directly dephosphorylate several members of the AGC family of kinases, which are important regulators of cell growth, proliferation, and survival. We have previously demonstrated that removal of PHLPP1 increases Akt activity in neonatal rat ventricular myocytes (NRVMs) (Miyamoto et al 2010) as well as the heart (Moc et al 2015) leading to protection from pathological hypertrophy and damage, however the effects of PHLPP2 removal on cardiomyocyte hypertrophic growth are unknown. In NRVMs, we found that removal of PHLPP2 induced hypertrophic growth basally without altering Akt activity and immunoprecipitation experiments revealed a novel interaction with an AGC kinase, G-protein coupled receptor kinase 5 (GRK5). GRK5 acts as an HDAC kinase downstream of phenylephrine (PE) to regulate hypertrophy in NRVMs. Thus, our objective was to determine whether PHLPP2 regulates PE-induced cardiomyocyte hypertrophy through its interaction with GRK5. We found that knockdown of PHLPP2, not PHLPP1, potentiated PE-induced hypertrophy (siPH2+PE (109 ± 3.5μm) vs. siCon+PE (88 ± 1.9μm)), and increased mRNA expression of fetal genes (i.e. ANF and BNP). Conversely, overexpression of PHLPP2 attenuated PE-induced hypertrophic growth (PH2+PE (66.6 ±7.7μm) vs. GFP+PE (95.5 ± 2.7μm)) as well as fetal gene re-expression. This inhibition of hypertrophic growth was dependent on phosphatase activity since a PHLPP2 mutant lacking the phosphatase domain (αPP2C) reversed the effect of PHLPP2 overexpression. To determine whether removal of PHLPP2 alters GRK5 translocation, cells were fractionated, and we found that PHLPP2 removal significantly increased basal and PE-induced nuclear accumulation of GRK5 that was blocked by overexpression of PHLPP2. Finally, knockdown studies with siGRK5 revealed that GRK5 was indeed required for the hypertrophic response elicited by PHLPP2 removal. Overall, our data revealed for the first time that PHLPP2 plays a role in regulating PE-induced cardiac hypertrophy via a GRK5 dependent pathway. Understanding the biological function and signaling pathways altered by PHLPP2 in cardiomyocytes may help delineate therapeutic targets for cardiac hypertrophy.
IMPACT OF CHRONIC KIDNEY DISEASE ON CLINICAL AND HEALTH STATUS OUTCOMES AFTER CHRONIC TOTAL OCCLUSION PERCUTANEOUS CORONARY INTERVENTION
Authors: Ali O. Malik, Poghni Peri-Okonny, James Grantham, William Lombardi, Dimitrios Karmpaliotis, Jeffrey Moses, William Nicholson, John A. Spertus, Adam Salisbury
Journal: Journal of the American College of Cardiology (2019)
On Demand Recruitment of Macrophages Is Required for Erythroid Niche Formation during Stress Erythropoiesis in the Bone Marrow
Authors: Verena Petzer, Piotr Tymoszuk, Felix Böhm, Markus Seifert, Sieghart Sopper, Christa Pfeifhofer-Obermair, Natascha Brigo, Dominik Wolf, Günter Weiss, Igor Theurl
Journal: Blood (2018)
SEXUAL DIMORPHISM IN CARDIOMETABOLIC STATUS AND CARDIAC MITOCHONDRIAL FUNCTION IN OBESE-INSULIN RESISTANT RATS FOLLOWING SEX HORMONE DEPRIVATION
Authors: Krekwit Shinlapawittayatorn, Wanpitak Pongkan, Sivaporn Sivasinprasasn, Siriporn Chattipakorn, Nipon Chattipakorn
Journal: Journal of the American College of Cardiology (2019)
IMPAIRED RISE IN CARDIAC OUTPUT ON DOBUTAMINE STRESS ECHOCARDIOGRAPHY PREDICTS DEVELOPMENT OF HEPATORENAL SYNDROME
Authors: Anoop Ninan Koshy, Benjamin Cailes, Jithin Sajeev, Jay Ramchand, Paul Calafiore, Hamid Salehi, Paul J. Gow, Piyush Srivastava, Hui-Chen Han, Jefferson Ko, Han Lim, Andrew Teh, Adam Testro, H.M. Omar Farouque
Journal: Journal of the American College of Cardiology (2019)
Evolutionarily significant A-to-I RNA editing events originated through G-to-A mutations in primates
Authors: Ni A. An, Wanqiu Ding, Xin-Zhuang Yang, Jiguang Peng, Bin Z. He, Qing Sunny Shen, Fujian Lu, Aibin He, Yong E. Zhang, Bertrand Chin-Ming Tan, Jia-Yu Chen, Chuan-Yun Li
Journal: Genome biology (2019)

Recent studies have revealed thousands of A-to-I RNA editing events in primates, but the origination and general functions of these events are not well addressed. Here, we perform a comparative editome study in human and rhesus macaque and uncover a substantial proportion of macaque A-to-I editing sites that are genomically polymorphic in some animals or encoded as non-editable nucleotides in human. The occurrence of these recent gain and loss of RNA editing through DNA point mutation is significantly more prevalent than that expected for the nearby regions. Ancestral state analyses further demonstrate that an increase in recent gain of editing events contribute to the over-representation, with G-to-A mutation site as a favorable location for the origination of robust A-to-I editing events. Population genetics analyses of the focal editing sites further reveal that a portion of these young editing events are evolutionarily significant, indicating general functional relevance for at least a fraction of these sites. Overall, we report a list of A-to-I editing events that recently originated through G-to-A mutations in primates, representing a valuable resource to investigate the features and evolutionary significance of A-to-I editing events at the population and species levels. The unique subset of primate editome also illuminates the general functions of RNA editing by connecting it to particular gene regulatory processes, based on the characterized outcome of a gene regulatory level in different individuals or primate species with or without these editing events.
THE RELATIONSHIP BETWEEN LIPOPROTEIN(A) AND PROGRESSION OF AORTIC STENOSIS IN A LARGE DYSLIPIDEMIC POPULATION
Authors: Nishant Shah, Leslie Cho, Mohamed Khayata, Haris Riaz, Risheek Kaul, Antonette Karrthik, Steven Nissen, Haitham Ahmed
Journal: Journal of the American College of Cardiology (2019)
Concurrent FLT3 Inhibitor and PP2A Activating Drug Treatment Induces Synergistic Cytotoxicity in Acute Myeloid Leukemia Cells with FLT3 Internal Tandem Duplication through Proteasomal Degradation of Pim-1 and c-Myc
Authors: Mario Scarpa, Shivani Kapoor, Danilo Perrotti, Maria R. Baer
Journal: Blood (2018)
PCSK9 INHIBITOR AND ATORVASTATIN IMPROVE CARDIAC AND MITOCHONDRIAL FUNCTION IN OBESE-INSULIN RESISTANT RATS
Authors: Patchareeya Amput, Siripong Palee, Busarin Arunsak, Wasana Pratchayasakul, Thidarat Jaiwongkam, Siriporn Chattipakorn, Nipon Chattipakorn
Journal: Journal of the American College of Cardiology (2019)
Immunogenicity and safety of measles-rubella vaccine co-administered with attenuated Japanese encephalitis SA 14–14–2 vaccine in infants aged 8 months in China: a non-inferiority randomised controlled trial
Authors: Yan Li, Susan Y Chu, Chenyan Yue, Kathleen Wannemuehler, Shuyun Xie, Fubin Zhang, Yamin Wang, Yuxi Zhang, Rui Ma, Yumin Li, Zhiping Zuo, Lance Rodewald, Qiyou Xiao, Zijian Feng, Huaqing Wang, Zhijie An
Journal: The Lancet Infectious Diseases (2019)
DO IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR HEART FAILURE DIAGNOSTICS PREDICT FAILURE OF MONOMORPHIC VENTRICULAR TACHYCARDIA TO ANTI-TACHYCARDIA PACING AND NEED FOR SHOCK?
Authors: Mohammed Salim Al-Damluji, Meghan Snuckel, Ahmed Zaghloul, Corina Iorgoveanu, Aditi Singhvi, Jeffrey Kluger
Journal: Journal of the American College of Cardiology (2019)
Enhanced Fatty Acid Scavenging and Glycerophospholipid Metabolism Accompany Melanocyte Neoplasia Progression in Zebrafish
Authors: Fiona Henderson, Hannah R. Johnston, Andrew P. Badrock, Emrys A. Jones, Duncan Forster, Raghavendar T. Nagaraju, Christos Evangelou, Jivko Kamarashev, Michael Green, Michael Fairclough, Irene Barinaga-Rementeria Ramirez, Shuning He, B. Ewa Snaar-Jagalska, Katherine Hollywood, Warwick B. Dunn, Herman P. Spaink, Michael P. Smith, Paul Lorigan, Emmanuelle Claude, Kaye J. Williams, Adam W. McMahon, Adam Hurlstone
Journal: Cancer Research (2019)

Abstract Alterations in lipid metabolism in cancer cells impact cell structure, signaling, and energy metabolism, making lipid metabolism a potential diagnostic marker and therapeutic target. In this study, we combined PET, desorption electrospray ionization-mass spectrometry (DESI-MS), nonimaging MS, and transcriptomic analyses to interrogate changes in lipid metabolism in a transgenic zebrafish model of oncogenic RAS-driven melanocyte neoplasia progression. Exogenous fatty acid uptake was detected in melanoma tumor nodules by PET using the palmitic acid surrogate tracer 14(R,S)-18F-fluoro-6-thia-heptadecanoic acid ([18F]-FTHA), consistent with upregulation of genes associated with fatty acid uptake found through microarray analysis. DESI-MS imaging revealed that FTHA uptake in tumors was heterogeneous. Transcriptome and lipidome analyses further highlighted dysregulation of glycerophospholipid pathways in melanoma tumor nodules, including increased abundance of phosphatidyl ethanolamine and phosphatidyl choline species, corroborated by DESI-MS, which again revealed heterogeneous phospholipid composition in tumors. Overexpression of the gene encoding lipoprotein lipase (LPL), which was upregulated in zebrafish melanocyte tumor nodules and expressed in the majority of human melanomas, accelerated progression of oncogenic RAS-driven melanocyte neoplasia in zebrafish. Depletion or antagonism of LPL suppressed human melanoma cell growth; this required simultaneous fatty acid synthase (FASN) inhibition when FASN expression was also elevated. Collectively, our findings implicate fatty acid acquisition as a possible therapeutic target in melanoma, and the methods we developed for monitoring fatty acid uptake have potential for diagnosis, patient stratification, and monitoring pharmacologic response. Significance: These findings demonstrate the translational potential of monitoring fatty acid uptake and identify lipoprotein lipase as a potential therapeutic target in melanoma.
PATIENTS WITH DIABETES AND PERIPHERAL ARTERIAL DISEASE: RESULTS FROM THE EXSCEL TRIAL
Authors: Anish Badjatiya, Peter Merrill, John Buse, Shaun Goodman, Brian Katona, Nayyar Iqbal, Peter Ohman, Neha Pagidipati, Naveed Sattar, Rury Holman, Adrian Hernandez, Robert J. Mentz, Manesh Patel, Schuyler Jones
Journal: Journal of the American College of Cardiology (2019)
Immune cells as targets for cardioprotection: new players and novel therapeutic opportunities
Authors: Ioanna Andreadou, Hector A Cabrera-Fuentes, Yvan Devaux, Nikolaos G Frangogiannis, Stefan Frantz, Tomasz Guzik, Elisa A Liehn, Clarissa P C Gomes, Rainer Schulz, Derek J Hausenloy
Journal: Cardiovascular Research (2019)

New therapies are required to reduce myocardial infarct (MI) size and prevent the onset of heart failure in patients presenting with acute myocardial infarction (AMI), one of the leading causes of death and disability globally. In this regard, the immune cell response to AMI, which comprises an initial pro-inflammatory reaction followed by an anti-inflammatory phase, contributes to final MI size and post-AMI remodelling [changes in left ventricular (LV) size and function]. The transition between these two phases is critical in this regard, with a persistent and severe pro-inflammatory reaction leading to adverse LV remodelling and increased propensity for developing heart failure. In this review article, we provide an overview of the immune cells involved in orchestrating the complex and dynamic inflammatory response to AMI-these include neutrophils, monocytes/macrophages, and emerging players such as dendritic cells, lymphocytes, pericardial lymphoid cells, endothelial cells, and cardiac fibroblasts. We discuss potential reasons for past failures of anti-inflammatory cardioprotective therapies, and highlight new treatment targets for modulating the immune cell response to AMI, as a potential therapeutic strategy to improve clinical outcomes in AMI patients. This article is part of a Cardiovascular Research Spotlight Issue entitled 'Cardioprotection Beyond the Cardiomyocyte', and emerged as part of the discussions of the European Union (EU)-CARDIOPROTECTION Cooperation in Science and Technology (COST) Action, CA16225.
OBESITY DOES NOT PREDICT LONG TERM OUTCOMES IN MINIMALLY INVASIVE MITRAL VALVE SURGERY FOR DEGENERATIVE MITRAL VALVE DISEASE
Authors: Neal Foley, Renaldo Williams, Rushikesh Vyas, Leslie Busbee, Shi Huang, Keki Balsara, Clayton Allen Kaiser, Michael Petracek, Ashish Shah, Tarek Absi
Journal: Journal of the American College of Cardiology (2019)
Abstract P4-11-02: Subjective and objective assessment of efficacy of frozen gloves and socks to prevent nab-paclitaxel-induced peripheral neuropathy in patients with breast cancer
Authors: T Yamashita, M Hattori, T Nakada, T Hayashi, K Kamei, T Tatsuya, Y Nagao, T Mase, M Wada, T Mizuno, K Shimozuma, H Iwata, T Yamaguchi
Journal: Cancer Research (2019)

Abstract Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent side-effect of taxanes which play a central role in the treatment of breast cancer. CIPN can negatively influence long-term quality of life, warranting the development of effective prevention strategies. This study investigates the efficacy of frozen gloves and socks (FGS) in reducing the incidence and severity of nab-paclitaxel-induced peripheral neuropathy. Endpoints were evaluated using both clinician and patient reports. Methods: This is a multicenter phase II single arm trial study of the effects of FGS for advanced or metastatic breast cancer patients receiving nab-paclitaxel (260 mg/m2) every 3 weeks. Patients wore FGS on their diseased side hand and foot for 60 min during infusion. The other side acted as the untreated control. CIPN was assessed using Patient Neurotoxicity Questionnaire (PNQ), PRO-CTCAE and CTCAE at baseline and every cycle of nab-paclitaxel. The primary endpoint was the incidence of CIPN assessed by PNQ (grade C or higher) after receipt of up to 4 cycles of nab-paclitaxel. Results: Between September 2012 and January 2015, 50 patients from 16 sites were enrolled in this study. Of 50 patients, 27 (54%) received at least 4 cycles of nab-paclitaxel. There was a trend for the incidence of CIPN assessed by PNQ and PRO-CTCAE to be lower in the intervention side than in the control side, although this difference was not statistically significant. The incidence of CIPN assessed by CTCAE was significantly lower in the treated hand (Table). Conclusions: Among breast cancer patients who received nab-paclitaxel, FGS produced favorable effects as detected by reduced clinician-reported CTCAE grades for CIPN, although the study did not detect differences in self-reported symptoms of CIPN using PRO-CTCAE or PNQ. Clinical trial information: UMIN000007907. Difference according to the evaluation method of CIPN Hands (%) Feet (%) InterventionControlp*InterventionControlp*Patient-Reporting CIPNPNQ (grade C or higher)12190.3416160.63Patient-Reporting CIPNPRO-CTCAE Severity ≥ Moderate13180.0815160.56 Interference ≥ Somewhat7100.328100.32Clinician-Grading CIPNCTCAE (≥ Grade II)15190.0314131.0 *McNemar's test Citation Format: Yamashita T, Hattori M, Nakada T, Hayashi T, Kamei K, Tatsuya T, Nagao Y, Mase T, Wada M, Mizuno T, Shimozuma K, Iwata H, Yamaguchi T. Subjective and objective assessment of efficacy of frozen gloves and socks to prevent nab-paclitaxel-induced peripheral neuropathy in patients with breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-11-02.
Abstract 515: Bariatric Surgery Reverses Vascular Pathology in Mice With Morbid Obesity and Type 2 Diabetes
Authors: Yoonjung Park, Yong Wang1, Hanrui Zhang, Kevin D Dellsperger, Barry J Potter, Ji-min Cao, Cuihua Zhang
Journal: Circulation Research (2018)

Objective: The mechanism of improved insulin sensitivity and vascular function following bariatric surgery remains unclear. We assessed the role of bariatric surgery in coronary arteriolar function in murine type 2 diabetic mice. Approach and Results: The animals were randomly allocated into normal control (Lean) sham, Lean surgery, db/db sham, and db/db surgery (at 5, 10, 20 and 30 days post-operatively). Impaired vasodilation to acetylcholine (ACh) in db/db mice was partially restored by bariatric surgery. Ghrelin administration restored endothelium-dependent dilation in db/db mice, but surgery-induced restoration was disappeared by ghrelin antagonist. Additionally, the incubation of coronary arterioles with IL-6 prevented the restoration of ACh-induced vasodilation. Bariatric surgery attenuated plasma concentration and protein expression of IL-6 in db/db. Bariatric surgery increased protein expression of eNOS and SOD2 in db/db mice. Conclusions: Decreased IL-6 expression after bariatric surgery induce up-regulation of eNOS and SOD2, and down-regulation of iNOS and O 2 .− , leading to restoration of endothelial function in coronary arterioles in type 2 diabetes.
Дебют хвороби Крона проявами гострого апендициту
Authors: Ya.I. Lomei, V.I. Ludyn, Yu.Ya. Lomei, P.M. Romanchuk
Journal: GASTROENTEROLOGY (2020)

Проводиться аналіз сучасних поглядів на хворобу Крона (ХК). Наводиться випадок із практики раптового дебюту ХК проявами гострого апендициту у пацієнта молодого віку. Події відбувалися так: кумулюючий негативний вплив факторів ризику — гостра форма ХК із первинним ураженням черв’якоподібного відростка — клінічні прояви гострого апендициту — апендектомія — одужання, можливо, оманливе.
Human Bone Marrow Derived Mesenchymal Stromal Cells Enhance the Number and Function of Umbilical Cord Blood Peripheral Tregs during IL-2 Driven Ex Vivo Expansion
Authors: Jeong-Su Do, Alex Y. Huang, Daniel Zwick, Fei Zhong, David Askew, Wouter van't Hof, Marcie Finney, Mary Laughlin
Journal: Blood (2018)
Abstract 573: Mechanical Stress Alters Cell Signaling and Extracellular Matrix Genes in Fetal Cardiac Valves
Authors: Rebekah Macfie, Alex Bridges, Herbert M Espinoza, Isa Lindgren, Samantha Louey, George Giraud, Kent Thornburg, Frederick Tibayan
Journal: Circulation Research (2018)

Objective: Prenatal hypertension leads to mitral annular dilation and is linked to changes in valvular extracellular matrix (ECM) and cell cycle genes including TGFβ-1, BMPs and FGF. We hypothesized that these changes are exacerbated by additional mechanical stress. Methods: Fetal sheep received 8 days of plasma infusion to induce hypertension (HTN, n=5) or lactated ringers solution (CTRL, n=4) starting at 126±2 days gestational age (dGA; term~145 days). Fetal mitral valve interstitial cells (VICs) were isolated at 134±1dGA, cultured in flexible, collagen-coated wells and subjected to 0% (static) or 18% equibiaxial stretch (1 Hz, 24 hrs). mRNA was isolated and qPCR was used to determine the effects of HTN and stretch on gene expression. Statistical analysis was performed via two-way ANOVA with Bonferroni correction. Results: Plasma infusion significantly increased the MAP of HTN fetuses (44.3±2.4 vs 61.6±1.1mmHg, p= 0.002). Change in gene expression is shown in Fig. 1; data are expressed relative to the CTRL/static group. Stretch, but not HTN, significantly increased FGF expression (p&lt;0.05). HTN and stretch each significantly increased expression of TGFβ-1, BMP-1 and -2. Stretch amplified the hypertension-induced increase in these 3 genes (p&lt;0.05 for all). Versican was unaltered by HTN or stretch. Conclusion: Our study demonstrates that early exposure to mechanical stress can shape cell signaling pathway responses in developing fetal cardiac valves, and these changes are amplified when exposed to a secondary stress. These data indicate that the prenatal environment has implications for postnatal cardiac valve function and risk for valvular disease in adulthood.