tbuckley/cabot-search huggingface dataset:
Abstract 4203: Resting Heart Rate and its Changes Over Years as a Risk Factor for Mortality in the General Population: The Paris Prospective Study I
Authors: Xavier P Jouven, Jean Philippe Empana, Jean François Buyck, Florence Canoui Poitrine, Awa Kane, Christine Mouries, Dominique Courbon, Pierre Ducimetiere
Journal: Circulation (2006)

Background: Whether resting heart rate (HR) is a risk factor for mortality remains discussed. The aim of the study was to investigate whether HR changes are related to mortality in the population. Methods: 4320 native Frenchmen aged 42 to 53 years were recruited between 1967 and 1972, and had yearly examinations during the next 5 years in the same standardized conditions. Subjects had electrocardiograms and physical examinations conducted by a physician, provided blood samples for laboratory tests, and answered questionnaires administered by trained interviewers. Resting HR was determined by measurement of the radial pulse during a one-minute recording, after a five-minute rest in supine position. Results: During the follow-up period (&gt; 20 years) 1018 men died. Subjects were divided into 9 groups according to their baseline HR (≤ 60 bpm , 61–75, and &gt; 75 bpm) and to HR variation between baseline and the 5 th examination (decrease &gt; 7 bpm, low variation ie between − 7 and +7 bpm, and increase &gt; 7 bpm). Relative risks of mortality were estimated by Cox model after adjustments for age, physical activity, tobacco consumption, body mass index, systolic blood pressure, glycemia, and total cholesterol. Compared to the reference group (baseline HR between 61 and 75 bpm and low variation at the 5 th examination), baseline HR but also changes over years were both associated with the risk of death (table ). Conclusion: Our results show that resting HR and its changes are independent risk factors of mortality in the general population. mortality associated with resting heart rate and its trend
Abstract 4170: Inter- and Intra-Individual Variability in Glycemic Index Values for White Bread Determined Using Standardized Procedures
Authors: Sonia Vega-López, Lynne M Ausman, Susan M Jalbert, Alice H Lichtenstein
Journal: Circulation (2006)

Glycemic index (GI) values are used to classify carbohydrate-containing foods on the basis of serum glucose response relative to a glucose challenge, and both the GI and glycemic load (GL) values (GI adjusted for total carbohydrate) of diets have been used to estimate chronic disease risk. There is an underlying assumption that GI values for a given food are highly reproducible for an individual and similar among individuals. To test this hypothesis the inter- and intra-individual variability of GI values for white bread were assessed in twenty-three healthy adults (20–70 y) under controlled conditions using up to three sets of two challenges, white bread and glucose, administered in random order. Using the published standard protocol, the GI value was calculated by dividing the 2-h incremental area under the serum glucose response curve (AUC) for 50 g available carbohydrates from commercial white bread by the AUC for 50 g glucose. The mean GI value of the first set was 78 ± 73 (N=23), with an inter-individual coefficient of variation of 94%. The intra-individual reproducibility of the GI value for those subjects who completed three sets (n=14) was calculated using individual AUC values for white bread divided by the mean of the three AUC values after glucose, and were 78 ± 39, 60 ± 17 and 75 ± 37 for tests 1, 2 and 3, respectively. Inter-individual coefficients of variation were 50%, 29% and 50%, respectively. The mean GI value of these three sets was 71 ± 22, with an intra-individual coefficient of variation of 30%. These data suggest that despite the reduction in inter- and intra-individual variability with replicate testing, individual responses to a single food, white bread, are highly variable. Caution should be used in drawing conclusions on the basis of GI or GL values until there is a better understanding of inter- and intra-individual variability in response to individual foods and food mixtures.
Abstract 598: Activation of Volume-Sensitive Osmolyte/Anion Channels ( <i>VSOACs</i> ) Delays Progression from Myocardial Hypertrophy to Heart Failure
Authors: Lihui Liu, Guanlei Wang, Can Yuan, Jiani Xie, William J Hatton, Dayue Duan
Journal: Circulation (2006)

Background: In hypertrophied cardiac myocytes VSOAC s become constitutively activated. In this study, we used a murine line targeting ClC-3, a gene encoding native VSOACs in the heart, to explore the molecular mechanism for the potential role of VSOACs in pressure overload-induced myocardial hypertrophy and the progression to heart failure. Methods: A pressure overload model through a minimally invasive transverse aortic banding (MTAB) at the suprasternal notch level was established in age-matched ClCn3 −/− mice and their wild-type (WT) littermates. Echocardiography, whole-cell voltage-clamp technique, microarray (Affymetrix chips) and proteomic analysis were used to examine the changes in cardiac phenotype and in gene and protein expression profiles. Results: In 13/16 (81%) left ventricular myocytes isolated from WT mice subjected to MTAB for 5 weeks (wks) a large outwardly rectifying Cl − current was activated under isotonic conditions. Hypotonic cell swelling caused no changes in the current while it was significantly inhibited by hypertonic cell shrinkage or by intracellular dialysis of anti-ClC-3 antibody. The increase in wall thickness (myocardial hypertrophy) peaked significantly faster in ClCn3 −/− mice (&lt;1 wk) than in WT mice (&gt;4 wks). After MTAB the hypertrophied changes remained at a similar level for &gt;10 wks in WT mice, but heart failure accompanied by a significant decrease in wall thickness and increase in chamber dimensions developed in &lt;6 wks in ClCn3 −/− mice. Microarray and proteomic analyses in WT and ClCn3 −/− mouse myocardium pre and post MTAB for 1 and 5 wks revealed complex changes in gene and protein expression profiles involving not only ion channels but also cytoskeleton and signal transducer proteins. Conclusion: The constitutively activated VSOACs in hypertrophied heart may be due to ClC-3. Activation of VSOACs may delay the progression from myocardial hypertrophy to heart failure.
Abstract 5052: Attenuation of Ventricular Remodeling and Improvement of Left Ventricular Systolic Function by Injection of Human Fetal Cardiomyocyte Progenitor Cells After Acute Myocardial Infarction
Authors: Melina C den Haan, Robert W Grauss, Marie-Jose Goumans, Anke M Smits, Daniel A Pijnappels, Paul Steendijk, Adriana C Gittenberger-de Groot, Arnoud van der Laarse, Antoine A de Vries, Martin J Schalij, Pieter A Doevendans, Douwe E Atsma
Journal: Circulation (2009)

Introduction: The human cardiomyocyte progenitor cell (hCMPC) is part of a population of stem cells located in the human heart. Isolates of hCMPCs from human fetal hearts showed differentiation into functional cardiomyocytes in vitro. In the present study we investigated the potential of hCMPCs to restore ischemic myocardium and improve left ventricular (LV) function in a myocardial infarction (MI) model in mice. Methods: MI was induced in immune-compromised NOD/scid mice, immediately followed by injection of hCMPCs labeled with eGFP (hCMPC group) or vehicle only (control group). From sham operated mice we obtained reference values. Cardiac performance was measured 2 and 14 days after MI using 9.4 Tesla MRI. LV pressure-volume measurements were performed at day 15 followed by extensive immunohistological analysis. Results: Animals injected with hCMPCs after MI demonstrated a significantly higher LV ejection fraction, a lower LV end-systolic volume and a smaller ô (relaxation time constant), compared to animals from the control group (by 17%, by 22% and by 24% respectively, P&lt;0.05). A trend towards a lower LV end-diastolic volume was also observed, although this did not reach significance (P=0.14). Both the infarct zone and border zone of the hCMCP group showed a significant increase in total blood vessel density (6.67%±0.85% and 9.13%±0.46%) compared to control (3.35%±1.13% and 4.31%±1.08%, P&lt;0.01 in either zone). The infarct and border zone of the hearts injected with hCMPCs also had a diminished collagen type III density (1.07±0.06 and 1.11±0.07), compared to the control group (1.45±0.05 and 1.51±0.08, P&lt;0.01 in either zone). Furthermore, nuclear PCNA expression indicated an increased rate of mitosis in the infarct (37.76%±2.23%) and border zone (48.84%±2.07%) compared to the infarct (25.48%±4.83%, P&lt;0.01) and border zone (32.03%±1.03%, P&lt;0.01) of the control group. Conclusions: Fetal hCMPCs engraft into infarcted myocardium where they improve LV systolic function and attenuate ventricular remodeling. Increased blood vessel density, elevated mitosis rate and decreased collagen III deposition may be involved in this process. These results indicate that hCMPCs are promising candidates for cell-based therapy.
Abstract 5065: Statins Modulate the Expression of Kruppel-Like Factor 2 in T Lymphocytes and Inhibit T Cell Responses
Authors: De-xiu Bu, Guillermo Garcia-Cardena, Margarite Tarrio, Elena Maganto-Garcia, Nir Grabie, Andrew H Lichtman
Journal: Circulation (2009)

Kruppel-Like Factor 2 (KLF2) is a zinc -finger transcription factor, essential for maintenance of T cell quiescence and migration. Statins upregulate KLF2 expression in endothelial cells, but direct effects of statins on T cells are not characterized. We hypothesized that immunomodu-latory effects of statins are related partially to their influence on T cell KLF2 expression. Therefore, we characterized KLF2 expression pattern during different phases of T cell activation, examined the effects of Statins on KLF2 expression in T cells, and determined if Statins modulated pathologic T cell responses in a KLF2-dependent manner. Quantitative RT-PCR analyses indicated that KLF2 expression is relatively high in naïve mouse CD4+ and CD8+ T cells, but drops rapidly after TCR and CD28 co-stimulation and increases again as effector T cell are rested for several days. Interestingly, we also found that KLF2 is upregulated in CD8+ T cells that are functionally suppressed by FOXP3+ regulatory T cells. Effector T cells treated with four different lipophilic Statins (10 micromolar, 18h) enhanced expression of KLF2 and sphingosine 1 phosphate receptor (S1P1) and down-regulated interferon gamma expression. Statins also diminished T cell proliferation in response to TCR stimulation. Similar patterns of KLF2 expression and of Statin modulation of KLF2 were detected in human T cells, by qRT-PCR and Western blot analyses. Lovastatin (20mg/kg, i.p) treatment of C57B6 mice enhanced T cell KLF2 expression and induced resistance to T cell reactivation ex vivo. In a mouse model of myocarditis induced by adoptive transfer of heart-antigen-specific CTL, we found that simvastatin treatment of transferred T cells or retroviral-mediated over expression of KLF2 in the transferred T cells had similar effects; both reduced severity of myocarditis, down-regulated inflammatory gene expression in the hearts, and reduced cardiac draining lymph node responses. We conclude that both Statins and KLF2 modulate T cell activation and effector responses and that Statins upregulate KLF2 in T cells. Therefore, modulation of KLF2 by Statins may have therapeutic significance for cardiovascular diseases such as myocarditis and atherosclerosis.
Kynurenine Is a Novel Contributor to Hypotension in Human Sepsis
Authors: Dechaboon Changsirivathanathanathamrong
Journal: Circulation (2009)

Abstract #2366 Dechaboon Changsirivathanathanathamrong, Yutang Wang, Ctr for Vascular Res, Bosch Inst, Sydney, Australia; Dorrilyn Rajbhandari, Royal Prince Alfred Hosp, Sydney, Australia; Ghassan Maghzal, Ctr for Vascular Res, Bosch Inst, Sydney, Australia; Clive Woolfe, Royal Prince Alfred Hosp, Sydney, Australia; Val Gebski, NHMRC Clinical Trials Ctr, Sydney, Australia; David S Celermajer, Royal Prince Alfred Hosp, Bosch Inst, Sydney, Australia; Roland Stocker, Ctr for Vascular Res, Bosch Inst, Sydney, Australia Dechaboon Changsirivathanathanathamrong, 2009 Finalist and Presenting Author
Abstract 5074: The Rho Exchange Factor Arhgef1 in Vascular Smooth Muscle Cells is Essential for Angiotensin II-induced Hypertension
Authors: Christophe Guilluy, Jérémy Brégeon, Gilles Toumaniantz, Malvyne Rolli-Derkinderen, Kevin Retailleau, Laurent Loufrani, Daniel Henrion, Elizabeth Scalbert, Antoine Bril, Raul M Torres, Stephan Offermanns, Pierre Pacaud, Gervaise Loirand
Journal: Circulation (2009)

Rho exchange factors (Rho-GEFs) are responsible for Rho protein activation by catalyzing the exchange of GDP for GTP. Although over-activation of RhoA and its effector Rho kinase is recognized as a critical component of the pathogenesis of hypertension in experimental models and in human, the molecular mechanisms and the RhoA-GEF(s) involved in this activation of RhoA signaling in vascular smooth muscle cells (VSMCs) are unknown. Among the Rho-GEFs family, Arhgef1 (p115) constitutes with Arhgef11 (PDZ-Rho GEF) and Arhgef12 (Larg) the subfamily of RGS-containing Rho-GEFs that have been suggested to couple G-protein associated receptors to RhoA activation. To establish the role of Arhgef1 in the regulation of vascular tone and hypertension in vivo , we generated mice lacking Arhgef1 specifically in SMCs (SM-Arhgef1-KO). We used Arhgef1 lox/lox mice, which were mated to SMMHC-CreER T2 . SM-Arhgef1-KO mice were then obtained by treatment with tamoxifen (1 mg/day, IP, 5 days). In VSMCs from SM-Arhgef1-KO mice, stimulation with angiotensin II (Ang II, 0.1 μ M) was unable to induce RhoA/Rho kinase activation whereas that produced by U46619, phenylephrine (PhE), and endothelin-1 (ET1) was similar to that recorded in control mice. Ex vivo analysis of the contractile properties showed that, in aortic segments from SM-Arhgef1-KO mice, KCl-, PhE-, U46619- and ET1-induced contractions were similar to those obtained in control mice. In contrast, Ang II-induced contractions were severely reduced. In vivo, acute pressor responses to U46619 (3–100 μ g/kg), ET1 (0.03–1 μ g/kg) and PhE (0.1–100 μ g/kg) were similar in control and SM-Arhgef1-KO mice, but responses to Ang II (0.1–30 μ g/kg) were abolished. Basal blood pressure levels were similar in SM-Arhgef1-KO and control mice. In control mice, chronic infusion of Ang II (1 mg/kg/day) increased blood pressure whereas SM-Arhgef1-KO mice were resistant to the development of Ang II-induced hypertension. We therefore conclude that Arhgef1, as the molecular link between Ang II, RhoA activation and vascular tone regulation, provides an alternative target to reducing elevated vascular tone under hypertensive conditions without affecting normal blood pressure regulation by other vasoactive factors.
Abstract 4199: Influenza Vaccination in Prevention from Coronary Events in Coronary Artery Disease. FLUCAD Study.
Authors: Andrzej Ciszewski, Zofia T Bilinska, Lidia B Brydak, Magdalena Machala, Walerian Piotrowski, Ewa Ksiezycka, Renata Maczynska, Witold Ruzyllo
Journal: Circulation (2006)

Background: Influenza vaccination is recommended in patients (p) with cardiovascular disease, however there is few data proving its protective effect on clinical course of coronary artery disease (CAD). We present, to the best of our knowledge, first, randomized, double blind, placebo controlled study in this field. The aim of the study was to evaluate the effect of influenza vaccination on the incidence of coronary events in p with CAD confirmed by coronarography. Methods: Single center, randomized, prospective, double blind, placebo controlled study. The randomization was 1:1 (placebo : active vaccine). Cox proportional hazards model analysis was performed. Study group: Between October 2004 and February 2005, we included and vaccinated 658 CAD p; 477 men, mean age 59.9+/−10.3 years. There were 287 p enrolled before discharge from the hospital after percutaneous coronary intervention (PCI), and 371 p without recent PCI. Results: 325 p received the active vaccine, and 333 p received placebo. There were no significant differences between the study groups. No patient was lost to follow-up. Mean follow-up was 296.8+/−35.7 days. Primary end-point: cardiovascular death occurred in 2 p (0.61%) in the vaccine vs in 2 p (0.60%) in the placebo group (NS). First composite end-point: cardiovascular death, or myocardial infarction, or non-planned coronary revascularization (PCI or coronary bypass surgery) tended to occur less frequently in the vaccine group in comparison to the placebo group: 9 p (2.8%) vs 17 p (5.1%), respectively, (HR 0.54; 95% CI, 0.24 to 1.21; p= 0.13). Second composite end-point: cardiovascular death, or myocardial infarction, or non-planned revascularization or hospitalization for ischemia occurred significantly less frequently in the vaccine group: 16 p (4.9%) vs 30 p (9.0%) in the placebo group, (HR 0.54; 95% CI, 0.29 to 0.991; p=0.047). On multivariate analysis : primary PCI (HR 2.93; 95% CI 1.51 − 5.65, p=0.0014), influenza vaccination (HR 0.38; 95% CI 0.19 − 0.78, p=0.009), and female sex (HR 2.15; 95% CI 1.11 − 4.15, p=0.023), emerged as independent predictors of the occurrence of composite point 2. Conclusion: Influenza vaccination may reduce frequency of coronary events in patients with coronary artery disease.
Abstract 4162: Cardiovascular Event Reduction Associated with Achieving Optimal Values for Multiple Lipids
Authors: Richard Karas, Mark J Cziraky, Ralph Quimbo, Scott L Charland, William Insull, Michael H Davidson, Eric J Stanek
Journal: Circulation (2006)

Introduction : We hypothesized that achievement of optimal lipid values would significantly reduce the risk of CV event relative to patients with combined non-optimal lipid profiles, across patients with specific lipid abnormalities. Methods : Retrospective analyses were conducted in patients ≥18 y/o with a lipid panel between 01/00–12/01 and ≥1 f/u panel through 06/04, ≥12 months continuous data pre- and post-initial lipid panel, and without dyslipidemia associated drug therapy. Optimal lipid values were defined as (mg/dL): LDL-C &lt;100/&lt;130 per CV risk level; HDL-C &gt;40 men/&gt;50 women; TG &lt;200. Three cohorts were constructed -Cohort 1: non-optimal LDL-C; Cohort 2: non-optimal LDL-C and either non-optimal TG or HDL-C; and Cohort 3: non-optimal LDL-C, HDL-C, and TG. The primary outcome was risk of CV event, defined as any emergency or inpatient visit with ICD-9 codes corresponding to ischemic heart disease, peripheral vascular disease, and stroke/TIA. The relative risk of CV events in patients achieving versus not achieving combined optimal lipid values were determined using adjusted Cox proportional-hazards models, adjusted for age, sex, CV comorbidities, and dyslipidemia treatment. Results : Events (3,956 total) were recorded over an average of 2.7 years in 23,234 at risk patients with suboptimal baseline lipid values. Decreasingly lower percentages of combined optimal lipid values were attained across cohorts as the number of suboptimal baseline lipid values increased (all p&lt;0.001). While correction of baseline lipids with achievement of combined optimal lipid values was infrequent, it was associated with a significant CV risk reduction of 25% in patients with abnormal LDL-C only and 46% in patients with LDL-C + HDL-C and/or TG abnormalities. Conclusion : Lifestyle and pharmacotherapy interventions sufficient to render LDL-C, HDL-C and TG optimal may substantially improve CV outcomes in patients with both simple and multiple lipid abnormalities.
Abstract 591: Non-Invasive Analysis of Oxidative Stress in Myocardial Remodeling and Failure in Mice Using in vivo Electron Spin Resonance (ESR) Spectroscopy
Authors: Tomomi Ide, Mayumi Yamato, Masayoshi Yoshida, Hideo Utsumi, Ikeuchi Masaki, Takaki Tsutsumi, Takahiro Inoue, Takeshi Shiba, Hiroyuki Tsutsui, Kenji Sunagawa
Journal: Circulation (2006)

Oxidative stress plays an important role in the development and progress of myocardial remodeling and failure. We have demonstrated that the generation of reactive oxygen species (ROS) is enhanced in the tissue homogenates obtained from the failing hearts in vitro by electron spin resonance (ESR) spectroscopy (Ide, Circ Res 2000, 86, 152). However, there is no direct evidence of ROS generation in the hearts in vivo. Therefore, the aim of this study was to assess the time-dependent changes of ROS generation in the hearts after myocardial infarction(MI) using a technique of in vivo ESR measurement that has been developed for direct and non-invasive analysis of ROS generation in living animals.We created MI in mice by ligating the left coronary artery and performed in vivo ESR analysis at day 2, 7, 14, and 28 after MI. The in vivo generation of ROS was analyzed by the ESR signal decay of methoxy-PROXYL, a tissue permeable spin probe, injected intravenously. Left ventricular (LV) function was assessed by echocardiography. The ESR signal decay measured at the chest of mice was not changed in MI at day 2, but was increased in MI compared to sham-operated mice at day 7 (Sham vs MI; 0.122±0.005 vs 0.142±0.007/min; p&lt;0.05)and further increased at day 14(0.123±0.004 vs 0.162±0.009/min, p&lt;0.01) and 28 (0.119±0.004 vs 0.161±0.010/min, p&lt;0.01). The accelerated ESR signal decay was associated with the progression of LV dilatation and dysfunction. The increased ESR signal decay in MI was completely suppressed by the administration of antioxidant, Tiron. The ESR signal decay was comparable between groups when measured at the head or the abdomen, indicating that the increase of the signal decay was due to the ROS generation within the heart. It was further confirmed by the increased ESR signal decay in the cardiac homogenates obtained from MI mice. The present study provided the direct evidence in the post-MI living mice that ROS were generated within the hearts during the progression of remodeling and failure.
Multipotent Mesenchymal Stem Cells Contribute to Vascular Remodeling in Patients With Chronic Thromboembolic Pulmonary Hypertension
Authors: Amy L Firth
Journal: Circulation (2009)

Abstract #2365 Amy L Firth, Weijuan Yao, Aiko Ogawa, Michael M Madani, Grace L Lin, Jason X-J Yuan, Univ of California, San Diego, La Jolla, CA Amy L Firth, 2009 Finalist and Presenting Author