tbuckley/cabot-search huggingface dataset:
Insulin-Mediated Upregulation of the Renin Angiotensin System in Human Subcutaneous Adipocytes Is Reduced by Rosiglitazone
Authors: AlisonHarte, PhilipMcTernan, RajkumarChetty, SimonCoppack, JonathanKatz, StephenSmith, SudheshKumar
Journal: Circulation (2005)

Background— Obesity-associated hypertension is likely to be due to multiple mechanisms. Identification of the renin-angiotensin system (RAS) within adipose tissue does, however, suggest a potential causal role for it in obesity-associated hypertension. Obese patients are often hyperinsulinemic, but mechanisms underlying insulin upregulation of the RAS in adipose tissue are unclear. Tumor necrosis factor-α (TNF-α), an inducer of angiotensinogen in hepatocytes, is elevated in hyperinsulinemic, obese individuals and may provide a link in mediating insulin upregulation of the RAS in adipose tissue. Furthermore, thiazolidinediones lower blood pressure in vivo, and downregulation of the RAS in adipose tissue may contribute to this effect. We therefore examined the effect of rosiglitazone (RSG) on the insulin-mediated upregulation of the RAS. Methods and Results— Sera were obtained from the arterial circulation and from venous blood by draining subcutaneous abdominal adipose tissue. Isolated human abdominal subc...
Pioneering Effects and Enhanced Neurite Complexity of Primary Hippocampal Neurons on Hierarchical Neurotemplated Scaffolds
Authors: Beom Jin Kim, Matthew Park, Ji Hun Park, Sunghoon Joo, Mi‐Hee Kim, Kyungtae Kang, Insung S. Choi
Journal: Advanced Healthcare Materials (2018)

Abstract In this work, the use of scaffolds is reported, templated from live neurons as an advanced culture platform for primary neurons. Hippocampal neurons cultured on neurotemplated scaffolds exhibit an affinity for templated somas, revealing a preference for micrometric structures amidst nanotopographical features. It is also reported, for the first time, that neurite complexity can be topographically controlled by increasing the density of nanometric features on neurotemplated scaffolds. Neurotemplated scaffolds are versatile, hierarchical topographies that feature biologically relevant structures, in both form and scale, and capture the true complexity of an in vivo environment. The introduction and implementation of neurotemplated scaffolds is sure to advance research in the fields of neurodevelopment, network development, and neuroregeneration.
Therapeutic Engagement of the Histone Deacetylase IIA–Myocyte Enhancer Factor 2 Axis Improves Experimental Pulmonary Hypertension
Authors: Avraham Sofer, Seyoung Lee, Irinna Papangeli, Takaomi Adachi, Cheol Hwangbo, Suzy Comhair, Paul DaSilva-Jardine, Jongmin Kim, John J. Schwarz, Serpil C. Erzurum, Hyung J. Chun
Journal: American Journal of Respiratory and Critical Care Medicine (2018)
Electrogenic Suppression of Automaticity in Sheep and Dog Purkinje Fibers
Authors: Mariovassalle
Journal: Circulation Research (1970)

Driving Purkinje fibers at a fast rate is followed by a temporary suppression of spontaneous activity,  suppression. The mechanism of this suppression was studied in Purkinje fibers perfused in vitro and stimulated for variable periods of time at selected rates. The overdrive procedures caused an initial decrease in maximum diastolic potential below control followed by a late increase above control. After the overdrive, the slope of diastolic depolarization was decreased and the threshold voltage more positive2, these changes were responsible for the temporary suppression of spontaneous activity. After the cessation of 2-minute overdrive, the increase in maximum diastolic potential subsided gradually over a period of 2 to 5 minutes. At higher [K]o, the effect of overdrive on membrane potential was reduced. Substitution of Na+ with Li+ or exposure to 2,4-dinitrophenol abolished the late hyperpolarization during overdrive. The membrane resistance was not altered after an overdrive period. The res...
Coexistence of Anti-Phospholipid Antibodies and Endothelial Perturbation in Systemic Lupus Erythematosus Patients With Ongoing Prothrombotic State
Authors: DomenicoFerro, ValerioPittoni, ClaudioQuintarelli, StefaniaBasili, MirellaSaliola, CostantinoCaroselli, GuidoValesini, FrancescoVioli
Journal: Circulation (1997)

Background Anti-phospholipid antibodies (aPLs) were associated with an ongoing prothrombotic state in patients with systemic lupus erythematosus (SLE). Because aPLs are able to shift endothelial function toward procoagulant activity in vitro, we investigated the relationship among aPLs, ongoing prothrombotic state, and endothelial perturbation in SLE patients. Methods and Results We measured aPLs, anti-EC antibodies, circulating levels of prothrombin fragment F1+2 (F1+2), tumor necrosis factor-α (TNF-α), tissue-type plasminogen activator (TPA), and von Willebrand factor (vWF) in 43 SLE patients and 25 healthy subjects. Patients positive for aPLs (n=23) had a higher prevalence of anti-EC antibodies (P=.02) and higher levels of F1+2 (P=.003) than aPL(−) patients. Endothelial perturbation, defined by elevated plasma levels of both TPA and vWF, was significantly associated with aPL positivity (P=.001). F1+2 >1 nmol/L (mean+2 SD of controls) was detected in all but one patient in whom aPL positivity and endoth...
Abstract 16866: Depressed Biventricular Outputs in Fetuses of Diabetic Mothers When Standardized to Estimated Fetal Weight
Authors: Jennifer Hickman, Mary Craft, Ling Li, Aparna Kulkarni, Lisa Hornberger, David Danford, Shelby Kutty
Journal: Circulation (2015)

Background: Although the results of maternal diabetes on the newborn heart are well described, in-utero cardiovascular effects of maternal diabetes and obesity are not as well understood. Hypothesis: Echocardiographically derived measures of right and left heart flow volumes in fetuses of diabetic mothers (FDM) and fetuses of obese mothers (FOM) differ from those of normal fetuses. Methods: We prospectively enrolled 264 normal fetuses, 30 FDM and 49 FOM for prenatal research echocardiography. Estimated fetal weight (EFW) based norms for aortic and pulmonary valve velocity time integrals (AVVTI, PVVTI), right and left ventricular outflow tract diameters (LVOTD, RVOTD), aortic and pulmonary valve stroke volume (AVSV, PVSV), and cardiac output (LVCO, RVCO) were derived from the 264 control group fetuses using nonlinear regression to a Gompertz growth function. Z values for each parameter were determined, then analyzed using a non-paired two-tailed t-test to compare the three groups. Results: The mean ± SD EFW (g) for normal fetuses, FDM and FOM were 1610 ± 1201, 964 ± 694 and 1075 ± 1013; respective mean gestational ages (weeks) were 28.1±1.3, 25.3± 5, and 25 ± 6.6. The table shows mean Z value comparisons of VTI, OTD, SV and CO for the RV and LV in the three groups. Conclusions: FDM have significantly lower right and left heart stroke volumes and outputs than other fetuses matched for size, while FOM did not have demonstrable right or left heart stroke volume or cardiac output changes relative to normal fetuses. Similar to their relationship with gestational age, normal right and left ventricular stroke volumes and outputs follow a non-linear correlation with estimated fetal weight. Flow volumes in macrosomic fetuses may be better normalized to EFW rather than to gestational age. Reduced placental blood flow and ventricular compliance changes may be contributing to depressed biventricular cardiac output in FDM.
Abstract 12740: CPR Training in Schools: What Can be Learned From Iowa’s Experience?
Authors: Derek B Hoyme, Dianne L Atkins
Journal: Circulation (2015)

Introduction: Survival from out of hospital cardiac arrest has remained almost constant at 10-12% over several decades. In a witnessed arrest, prompt initiation of bystander CPR has been demonstrated to double the chance of survival. Overall CPR training rates in the United States are low: 2.4% per year. Currently, 21 states have adopted legislation to increase CPR training in schools. Iowa has required CPR as a high school graduation requirement since 2011 through an unfunded mandate. The objective of this study is to understand the implementation process, practices and barriers to providing CPR education to high school students. We surveyed Iowa high schools to provide guidance for nascent programs based on 4 years of experience. Methods: A cross-sectional study was performed through surveys sent to 346 Iowa high schools using the Qualtrics™ online platform. A 20 question survey was developed to obtain descriptive data covering general demographics of the school, specifics of the CPR training programs including what year the program was implemented, who performs the training and in which setting it occurs, logistics and barriers to implementation, and AED training and availability. Results: Response rate was 24.3%, with a mean school size of 100-500 students and a mean faculty size of 25-50. When the law took effect in 2011, 51% of schools had training programs already in place, and currently 96% have successfully implemented CPR training. Perceived barriers to implementation were staffing, time commitment, cost, and equipment availability. The training facilitator was a school official or unpaid volunteer in 81% of schools, only 19% reported a paid instructor. Average estimated time commitment was 2 hours. The average estimated startup costs as well as yearly maintenance costs were &lt;$500 with funds usually allocated from existing school district funds. A low proportion of staff is trained in CPR: 69% of schools have less than 25 staff members who are CPR trained. AEDS are available in 98% of schools while only 61% include AED training in their training curriculum. Conclusions: Despite perceived barriers, school CPR training programs can be implemented with reasonable resource and time allocations.
Tranilast Suppresses Vascular Chymase Expression and Neointima Formation in Balloon-Injured Dog Carotid Artery
Authors: NaotakaShiota, HidekiOkunishi, ShinjiTakai, ImaoMikoshiba, HiroshiSakonjo, NobuoShibata, MizuoMiyazaki
Journal: Circulation (1999)

Background—Activation of vascular chymase plays a major role in myointimal hypertrophy after vascular injury by augmenting the production of angiotensin (ANG) II. Because chymase is synthesized mainly in mast cells, we assumed that the chymase-dependent ANG II formation could be downregulated by tranilast, a mast cell–stabilizing antiallergic agent. We have assessed inhibitory effects of tranilast on neointima formation after balloon injury in the carotid artery of dogs, which share a similar ANG II–forming chymase with humans, and further explored the pathophysiological significance of vascular chymase. Methods and Results—Either tranilast (50 mg/kg BID) or vehicle was orally administered to beagles for 2 weeks before and 4 weeks after balloon injury. Four weeks after the injury, remarkable neointima was formed in the carotid arteries of vehicle-treated dogs. Chymase mRNA levels and chymaselike activity of vehicle-treated injured arteries were increased 10.2- and 4.8-fold, respectively, those of uninjure...
Automatic Arrhythmia Identification Using Analysis of the Atrioventricular Association
Authors: MohanNair, NadirSaoudi, DanielKroiss, BriceLetac
Journal: Circulation (1997)

Background Atrioventricular association is a key criterion for arrhythmia diagnosis. Its use in a defibrillator should significantly reduce the incidence of inappropriate shocks. Therefore, we evaluated the diagnostic accuracy of an algorithm that uses dual-chamber sensing and analysis of atrioventricular association to discriminate ventricular from supraventricular arrhythmias in a prototype of an implantable defibrillator. Methods and Results The algorithm performed a stepwise analysis of arrhythmias. The rhythm was first classified on the basis of cycle lengths. Each episode was then classified as supraventricular or ventricular in origin on the basis of the stability of cycle lengths and atrioventricular association. This algorithm was evaluated in 156 episodes of induced sustained tachycardias. Eighty-nine tachycardias were taken from the Ann Arbor electrogram library; the others were recorded in 50 patients during electrophysiological studies. The atrial and ventricular signals were stored on an ext...
Impairment of Collateral Formation in Lipoprotein(a) Transgenic Mice
Authors: RyuichiMorishita, MinakoSakaki, KeiYamamoto, SotaIguchi, MotokuniAoki, KeitaYamasaki, KunioMatsumoto, ToshikazuNakamura, RichardLawn, ToshioOgihara, YasufumiKaneda
Journal: Circulation (2002)

Background— Although lipoprotein(a) (Lp[a]) is a risk factor for atherosclerosis, no study has documented the effects of Lp(a) on angiogenesis. In this study, we examined collateral formation in peripheral arterial disease (PAD) model in Lp(a) transgenic mice. In addition, we examined the feasibility of gene therapy by using an angiogenic growth factor, hepatocyte growth factor (HGF), to treat PAD in the presence of high Lp(a). Methods and Results— In Lp(a) transgenic mice, the degree of natural recovery of blood flow after operation was significantly lower than that in nontransgenic mice. Of importance, there was a significant negative correlation between serum Lp(a) concentration and the degree of natural recovery of blood flow (P<0.05). In addition, Lp(a) significantly stimulated the growth of vascular smooth muscle, accompanied by the phosphorylation of ERK. These data demonstrated the association of impairment of collateral formation with serum Lp(a) concentration. Thus, we examined the feasibility o...
Predictors of Poor Outcomes After Transcatheter Aortic Valve Replacement
Authors: Suzanne V. Arnold, Matthew R. Reynolds, Yang Lei, Elizabeth A. Magnuson, Ajay J. Kirtane, Susheel K. Kodali, Alan Zajarias, Vinod H. Thourani, Philip Green, Josep Rodés-Cabau, Nirat Beohar, Michael J. Mack, Martin B. Leon, David J. Cohen
Journal: Circulation (2014)

Background— Transcatheter aortic valve replacement (TAVR) is a less invasive option for treatment of high-risk patients with severe aortic stenosis. We sought to identify patients at high risk for poor outcome after TAVR using a novel definition of outcome that integrates quality of life with mortality. Methods and Results— Among 2137 patients who underwent TAVR in the PARTNER (Placement of Aortic Transcatheter Valve) trial or its associated continued access registry, quality of life was assessed with the Kansas City Cardiomyopathy Questionnaire–Overall Summary Scale (KCCQ-OS; range 0–100, where a higher score equates to a better quality of life) at baseline and at 1, 6, and 12 months after TAVR. A poor 6-month outcome (defined as death, KCCQ-OS score &lt;45, or ≥10-point decrease in KCCQ-OS score compared with baseline) occurred in 704 patients (33%). Using a split-sample design, we developed a multivariable model to identify a parsimonious set of covariates to identify patients at high risk for poor outcome. The model demonstrated moderate discrimination ( c -index=0.66) and good calibration with the observed data, performed similarly in the separate validation cohort ( c -index=0.64), and identified 211 patients (10% of the population) with a ≥50% likelihood of a poor outcome after TAVR. A second model that explored predictors of poor outcome at 1 year identified 1102 patients (52%) with ≥50% likelihood and 178 (8%) with ≥70% likelihood of a poor 1-year outcome after TAVR. Conclusions— Using a large, multicenter cohort, we have developed and validated predictive models that can identify patients at high risk for a poor outcome after TAVR. Although model discrimination was moderate, these models may help guide treatment choices and offer patients realistic expectations of outcomes based on their presenting characteristics. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00530894.
Early Relief of Chest Pain by Ethyl Chloride Spray in Acute Coronary Thrombosis
Authors: Janettravell
Journal: Circulation (1951)

Within a few minutes after its onset, intense pain of acute myocardial infarction was abolished by briefly spraying the precordium with ethyl chloride. Prompt relief of pain did not prevent tissue necrosis, but may have ameliorated the clinical course. We infer that the stimulus for pain in acute infarction is of extremely short duration but gives rise to a secondary, self-sustaining pain cycle which may be terminated by altering the flow of nerve impulses from the skin. The case also illustrates the increased susceptibility to digitalis which develops some days after myocardial infarction.
Inducible Nitric Oxide Synthase Modulates Cyclooxygenase-2 Activity in the Heart of Conscious Rabbits During the Late Phase of Ischemic Preconditioning
Authors: KenShinmura, Yu-TingXuan, Xian-LiangTang, EitaroKodani, HuiHan, YanqingZhu, RobertoBolli
Journal: Circulation Research (2002)

Cyclooxygenase-2 (COX-2) is known to mediate the cardioprotective effects of the late phase of ischemic preconditioning (PC); however, the signaling pathways involved in COX-2 induction following ischemic PC are unknown. In addition, although inducible nitric oxide synthase (iNOS) has been identified as a co-mediator of late PC together with COX-2, the interaction between iNOS and COX-2 in the heart is unknown. Using conscious rabbits, we found that the induction of COX-2 expression 24 hours after ischemic PC was blocked by pretreatment with inhibitors of protein kinase C (PKC), Src protein tyrosine kinases (PTKs), and nuclear factor-κB (NF-κB) but not by inhibitors of NOS or scavengers of reactive oxygen species (ROS). The selective iNOS inhibitors SMT and 1400W, given 24 hours after PC, abrogated the increase in myocardial prostaglandin E2 (PGE2) and 6-keto-PGF1α, whereas the selective soluble guanylate cyclase inhibitor ODQ had no effect. COX-2 selective inhibitors (celecoxib and NS-398) did not affect...
Abstract 3526: Beta-oxidation inhibition as a novel therapy for cisplatin-resistant ovarian cancer
Authors: Miran Rada, Jennifer Cha, Jessica Sage, Bo Zhou, Wei Yang, Zahra Ashkavand, Kenneth Norman, Sandra Orsulic, Dong-Joo Cheon
Journal: Cancer Research (2018)

Abstract Ovarian cancer is the most lethal gynecological cancer and affects one in 70 females in the United States during their lifetime. Cisplatin resistance is the major challenge in the treatment of ovarian cancer but the underlying mechanisms are not fully understood. The purpose of this study is to develop novel therapeutic strategies to treat cisplatin-resistant ovarian cancer. We identified collagen type XI alpha 1 (COL11A1) as a novel biomarker associated with cisplatin resistance in ovarian cancer. COL11A1 is highly expressed by cancer-associated fibroblasts adjacent to cancer cells as well as A2780CIS cisplatin-resistant ovarian cancer cell line. Our data show that COL11A1 binds to DDR2 in ovarian cancer cells and inhibits cisplatin-induced apoptosis in ovarian cancer cells. To obtain mechanistic insights underlying COL11A1-driven cisplatin resistance, we performed Tandem Mass Tag proteomic analysis of A2780CIS ovarian cancer cells before and after COL11A1 knockdown. Our proteomics data revealed that mitochondrial fatty acid β-oxidation was the most upregulated pathway by COL11A1 in ovarian cancer cells. Mitochondrial fatty acid β-oxidation is the major pathway that breaks down fatty acids to produce excess ATP and NADPH to support cell survival. Several studies suggested the association of β-oxidation with tumor cell proliferation in various cancers. However, the role of β-oxidation in ovarian cancer chemoresistance is largely unknown. Our results show that COL11A1 enhances the expression of not only fatty acid receptor CD36, but also key enzymes of fatty acid β-oxidation, such as CPT1A, HADHB, ACSL1 and ACAA2. Significantly, COL11A1-mediated overexpression of these proteins was diminished in the presence of shRNA against DDR2.We also confirmed that ovarian cancer cells increase both fatty acid uptake and oxygen consumption rate in response to palmitate in the presence of COL11A1. Importantly, inhibition of fatty acid β-oxidation using shRNA against CPT1A attenuated the function of COL11A1 in cisplatin resistance. Taken together, our results suggest that COL11A1 confers cisplatin resistance by increasing fatty acid β-oxidation in ovarian cancer cells. Our study uncovers fatty acid β-oxidation as a promising therapeutic target to treat cisplatin-resistant ovarian cancer, particularly cisplatin-resistant recurrent ovarian cancers which typically express high levels of COL11A1. Citation Format: Miran Rada, Jennifer Cha, Jessica Sage, Bo Zhou, Wei Yang, Zahra Ashkavand, Kenneth Norman, Sandra Orsulic, Dong-Joo Cheon. Beta-oxidation inhibition as a novel therapy for cisplatin-resistant ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3526.
Essential Role of Bone Marrow for Microvascular Endothelial and Metabolic Functions in Mice
Authors: SotaNakajima, JunkoOhashi, AyukoSawada, KazukiNoda, YoshihiroFukumoto, HiroakiShimokawa
Journal: Circulation Research (2012)

Rationale:We have previously demonstrated that the importance of endothelium-derived hyperpolarizing factor (EDHF) increases as the vessel size decreases and that endothelium-derived hydrogen peroxide (H2O2) is an EDHF in animals and humans, for which endothelial nitric oxide synthase (eNOS) is the major source. Recent studies have suggested the important role of the bone marrow (BM) in modulating cardiovascular and metabolic functions. Objective:We aimed to examine whether BM plays a role in modulating microvascular endothelial and metabolic functions in mice, and if so, to elucidate the mechanisms involved. Methods and Results:Male eNOS−/− mice were transplanted with BM cells from wild-type (WT) or eNOS−/− mice and were maintained for 6 weeks. Endothelium-dependent relaxations and hyperpolarizations of mesenteric arteries to acetylcholine were reduced in eNOS−/− mice and were markedly improved when transplanted with WT-BM but not with eNOS−/−-BM. The enhanced component of endothelium-dependent relaxatio...