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  • American Heart Association (AHA)  (46)
  • American Association for the Advancement of Science (AAAS)  (35)
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  • 1
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    Common Genetic Variants of MGP Are Associated With Calcification on the Arterial Wall but Not With Calcification Present in the Atherosclerotic Plaques [Original Articles] (2013)
    American Heart Association (AHA)
    Details
    Publication Date: 2013-06-19
    Description: Background— Two endophenotypes of arterial calcification, calcification on arterial wall and calcification in atherosclerotic plaques, are associated with different types of cardiovascular events. Mgp -deficient mice showed matrix Gla protein (MGP) is strongly associated with calcification on arterial wall without atherosclerotic plaques, and MGP variants were not significantly associated with myocardial infarction. MGP may play different roles in the 2 endophenotypes. Methods and Results— We analyzed the associations of MGP variants rs4236, rs1800801, and rs1800802 with the 2 endophenotypes determined by multidetector computed tomography angiography. A total of 585 with calcification on coronary artery wall, 675 with calcification in coronary atherosclerotic plaques, 454 with calcification on aortic wall, and 725 controls were enrolled. After Bonferroni correction, rs4236 and rs1800801 were still associated with calcification on arterial wall, the odds ratios were 0.708 (95% confidence interval, 0.540–0.928) for rs4236 and 0.652 (95% confidence interval, 0.479–0.888) for rs1800801 in coronary artery wall calcification, and 0.699 (95% confidence interval, 0.525–0.931) for rs4236 and 0.650 (95% confidence interval, 0.467–0.905) for rs1800801 in aortic wall calcification, respectively. The variants were correlated with calcification severity by ln(CAC Agatston score+1) in coronary artery wall calcification but not in atherosclerotic plaque calcification. In accordance with their associations with calcification on arterial wall, rs4236C and rs1800801A were associated with higher MGP plasma levels, whereas rs1800802C was associated with lower MGP levels in normal controls. Because of the role of calcification in plaque vulnerability, their associations with acute myocardial infarction were also determined in 771 controls and 752 patients, no association was found. Conclusions— MGP genetic variants showed association with calcification on arterial wall but not with calcification in atherosclerotic plaques.
    Keywords: Clinical genetics, Risk Factors, Acute myocardial infarction, Other Vascular biology
    Print ISSN: 1942-325X
    Electronic ISSN: 1942-3268
    Topics: Medicine
    Published by American Heart Association (AHA)
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  • 2
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    Anderson localization of electrons in single crystals: LixFe7Se8 (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-02-21
    Description: Anderson (disorder-induced) localization, proposed more than half a century ago, has inspired numerous efforts to explore the absence of wave diffusions in disordered media. However, the proposed disorder-induced metal-insulator transition (MIT), associated with the nonpropagative electron waves, has hardly been observed in three-dimensional (3D) crystalline materials, let alone single crystals. We report the observation of an MIT in centimeter-size single crystals of Li x Fe 7 Se 8 induced by lattice disorder. Both specific heat and infrared reflectance measurements reveal the presence of considerable electronic states in the vicinity of the Fermi level when the MIT occurs, suggesting that the transition is not due to Coulomb repulsion mechanism. The 3D variable range hopping regime evidenced by electrical transport measurements at low temperatures indicates the localized nature of the electronic states on the Fermi level. Quantitative analyses of carrier concentration, carrier mobility, and simulated density of states (DOS) fully support that Li x Fe 7 Se 8 is an Anderson insulator. On the basis of these results, we provide a unified DOS picture to explain all the experimental results, and a schematic diagram for finding other potential Anderson insulators. This material will thus serve as a rich playground for both theoretical and experimental investigations on MITs and disorder-induced phenomena.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    A single transcription factor promotes both yield and immunity in rice (2018)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2018-09-07
    Description: Plant immunity often penalizes growth and yield. The transcription factor Ideal Plant Architecture 1 (IPA1) reduces unproductive tillers and increases grains per panicle, which results in improved rice yield. Here we report that higher IPA1 levels enhance immunity. Mechanistically, phosphorylation of IPA1 at amino acid Ser 163 within its DNA binding domain occurs in response to infection by the fungus Magnaporthe oryzae and alters the DNA binding specificity of IPA1. Phosphorylated IPA1 binds to the promoter of the pathogen defense gene WRKY45 and activates its expression, leading to enhanced disease resistance. IPA1 returns to a nonphosphorylated state within 48 hours after infection, resuming support of the growth needed for high yield. Thus, IPA1 promotes both yield and disease resistance by sustaining a balance between growth and immunity.
    Keywords: Botany
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 4
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    Should More Significance Be Granted to Medication Response to Antihypertensives in Patients With Resistant Hypertension? [Letters to the Editor] (2014)
    American Heart Association (AHA)
    Details
    Publication Date: 2014-03-13
    Keywords: Cardiovascular Pharmacology, Other hypertension
    Print ISSN: 0194-911X
    Topics: Medicine
    Published by American Heart Association (AHA)
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  • 5
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    Nox2-Derived Superoxide Contributes to Cerebral Vascular Dysfunction in Diet-Induced Obesity [Basic Sciences] (2013)
    American Heart Association (AHA)
    In: Stroke
    Details
    Publication Date: 2013-10-22
    Description: Background and Purpose— Obesity is an increasing epidemic worldwide; however, little is known about effects of obesity produced by high-fat diet (HFD) on the cerebral circulation. The purpose of this study was to examine the functional and temporal effects of a HFD on carotid and cerebral vascular function and to identify mechanisms that contribute to such functional alterations. Methods— Responses of cerebral arterioles (in vivo) and carotid arteries (in vitro) were examined in C57Bl/6 (wild-type) and Nox2-deficient ( Nox2 –/– ) mice fed a control (10%) or a HFD (45% or 60% kcal of fat) for 8, 12, 30, or 36 weeks. Results— In wild-type mice, a HFD produced obesity and endothelial dysfunction by 12 and 36 weeks in cerebral arterioles and carotid arteries, respectively. Endothelial function could be significantly improved with Tempol (a superoxide scavenger) treatment in wild-type mice fed a HFD. Despite producing a similar degree of obesity in both wild-type and Nox2 –/– mice, endothelial dysfunction was observed only in wild-type, but not in Nox2 –/– , mice fed a HFD. Conclusions— Endothelial dysfunction produced by a HFD occurs in a temporal manner and appears much earlier in cerebral arterioles than in carotid arteries. Genetic studies revealed that Nox2-derived superoxide plays a major role in endothelial dysfunction produced by a HFD. Such functional changes may serve to predispose blood vessels to reduced vasodilator responses and thus may contribute to alterations in cerebral blood flow associated with obesity.
    Keywords: Animal models of human disease, Type 2 diabetes, Endothelium/vascular type/nitric oxide, Other Vascular biology
    Print ISSN: 0039-2499
    Electronic ISSN: 1524-4628
    Topics: Medicine
    Published by American Heart Association (AHA)
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  • 6
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    Subarachnoid Extension of Intracerebral Hemorrhage and 90-Day Outcomes in INTERACT2 [Brief Reports] (2013)
    American Heart Association (AHA)
    In: Stroke
    Details
    Publication Date: 2013-12-24
    Description: Background and Purpose— The prognostic significance of subarachnoid extension of intracerebral hemorrhage was determined in the INTEnsive blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT2) study. Methods— INTERACT2 was an open randomized controlled trial of early intensive compared with guideline-recommended blood pressure lowering in patients with elevated systolic blood pressure within 6 hours of intracerebral hemorrhage. Independent predictors of death or major disability (scores 3–6 on the modified Rankin Scale) at 90 days were analyzed in logistic regression models. Results— Of 2582 participants, 192 (7%) had subarachnoid extension, which was associated with larger hematoma volumes ( P 〈0.0001) and higher National Institute of Health Stroke Scale score ( P 〈0.0001). Subarachnoid extension predicted death or major disability at 90 days (71% versus 53%; unadjusted odds ratio, 2.25; 95% confidence interval, 1.63–3.10; P 〈0.0001). The association remained significant after adjusting for age, region, lipid-lowering therapy, systolic blood pressure, glucose, location of hematoma, intraventricular extension, and randomized treatment (odds ratio, 2.17; 95% confidence interval, 1.50–3.14; P 〈0.0001), but not after further adjustment for baseline hematoma volume ( P =0.62). Conclusions— Subarachnoid extension of intracerebral hemorrhage is associated with poor prognosis, which is determined by a larger volume of the underlying intraparenchymal hematoma. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00716079.
    Print ISSN: 0039-2499
    Electronic ISSN: 1524-4628
    Topics: Medicine
    Published by American Heart Association (AHA)
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  • 7
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    Regulators of G-Protein Signaling 10 and Heart Failure: The Importance of Negative Regulators of Heart Disease [Editorial Commentaries] (2015)
    American Heart Association (AHA)
    Details
    Publication Date: 2015-12-10
    Keywords: Cell Signaling/Signal Transduction, Hypertension
    Print ISSN: 0194-911X
    Topics: Medicine
    Published by American Heart Association (AHA)
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  • 8
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    Angiotensin-Converting Enzyme 3 (ACE3) Protects Against Pressure Overload-Induced Cardiac Hypertrophy [Heart Failure] (2016)
    American Heart Association (AHA)
    Details
    Publication Date: 2016-02-24
    Description: Background Angiotensin-converting enzyme 3 (ACE3) is a recently defined homolog of ACE. However, the pathophysiological function of ACE3 is largely unknown. Here, we aim to explore the role of ACE3 in pathological cardiac hypertrophy. Methods and Results Neonatal rat cardiomyocytes (NRCMs) with gain and loss of function of ACE3 and mice with global knockout or cardiac-specific overexpression of ACE3 were used in this study. In cultured cardiomyocytes, ACE3 conferred protection against angiotensin II (Ang II)-induced hypertrophic growth. Cardiac hypertrophy in mice was induced by aortic banding (AB) and the extent of hypertrophy was analyzed through echocardiographic, pathological, and molecular analyses. Our data demonstrated that ACE3-deficient mice exhibited more pronounced cardiac hypertrophy and fibrosis and a strong decrease in cardiac contractile function, conversely, cardiac-specific ACE3-overexpressing mice displayed an attenuated hypertrophic phenotype, compared with control mice, respectively. Analyses of the underlying molecular mechanism revealed that ACE3-mediated protection against cardiac hypertrophy by suppressing the activation of mitogen-activated protein kinase kinase (MEK)-regulated extracellular signal-regulated protein kinase (ERK1/2) signaling, which was further evidenced by the observation that inhibition of the MEK-ERK1/2 signaling by U0126 rescued the exacerbated hypertrophic phenotype in ACE3-deficient mice. Conclusions Our comprehensive analyses suggest that ACE3 inhibits pressure overload-induced cardiac hypertrophy by blocking the MEK-ERK1/2 signaling pathway.
    Keywords: Basic Science Research, Heart Failure, Hypertrophy, Remodeling
    Electronic ISSN: 2047-9980
    Topics: Medicine
    Published by American Heart Association (AHA)
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  • 9
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    Cystatin C Predicts Incident Cardiovascular Disease in Twins [Vascular Medicine] (2016)
    American Heart Association (AHA)
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    Publication Date: 2016-06-30
    Description: Background Cystatin C is associated with both renal function and atherosclerotic cardiovascular disease (ASCVD). We have previously shown a genetic correlation between cystatin C and prevalent ASCVD. The objective of this article is to study whether variation in cystatin C or creatinine predicts incident ASCVD when controlled for genetic factors. Methods and Results The predictive value of cystatin C and creatinine for incident ASCVD was studied in 11 402 Swedish twins, free of CVD at baseline, in an adjusted Cox-regression model during a median follow-up of 71 months. Twin pairs discordant for incident stroke, myocardial infarction and ASCVD during follow-up were identified and within-pair comparisons regarding cystatin C and creatinine levels were performed. We also investigated whether contact frequency and degree of shared environment influences were associated with similarity in cystatin C levels. In univariate analysis, cystatin C predicted incident ASCVD hazard ratio 1.57, 95% CI 1.47–1.67. When adjusted for traditional Framingham risk factors as covariates, cystatin C remained a predictor of incident stroke hazard ratio 1.45, 95% CI (1.25–1.70), ASCVD hazard ratio 1.26, 95% CI (1.13–1.41), and myocardial infarction hazard ratio 1.16, 95% CI (1.01–1.33). In twins discordant for incident stroke, cystatin C at baseline was higher in the twin who experienced a stroke compared to the healthy co-twin (1.11±0.3 mg/L versus 1.06±0.3 mg/L), whereas creatinine was lower in the twin who developed CVD compared to their healthy co-twins (76.1±16.9 μmol/L versus 79.4±20.3 μmol/L). Conclusions Variation in cystatin C relates to incident ASCVD and to stroke when adjusted for genetic confounding. In identical twins, cystatin C may be a sensitive marker of early hypertensive end-organ damage and small-vessel disease, whereas creatinine level may reflect nutritional status. The findings in disease-discordant monozygotic twins indicate that unique, possibly preventable, environmental factors are important.
    Keywords: Nephrology and Kidney, Cardiovascular Disease, Cerebrovascular Disease/Stroke, Atherosclerosis, Coronary Artery Disease
    Electronic ISSN: 2047-9980
    Topics: Medicine
    Published by American Heart Association (AHA)
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  • 10
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    A specialized flavone biosynthetic pathway has evolved in the medicinal plant, Scutellaria baicalensis (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-04-10
    Description: Wogonin and baicalein are bioactive flavones in the popular Chinese herbal remedy Huang-Qin ( Scutellaria baicalensis Georgi). These specialized flavones lack a 4'-hydroxyl group on the B ring (4'-deoxyflavones) and induce apoptosis in a wide spectrum of human tumor cells in vitro and inhibit tumor growth in vivo in different mouse tumor models. Root-specific flavones (RSFs) from Scutellaria have a variety of reported additional beneficial effects including antioxidant and antiviral properties. We describe the characterization of a new pathway for the synthesis of these compounds, in which pinocembrin (a 4'-deoxyflavanone) serves as a key intermediate. Although two genes encoding flavone synthase II (FNSII) are expressed in the roots of S . baicalensis , FNSII-1 has broad specificity for flavanones as substrates, whereas FNSII-2 is specific for pinocembrin. FNSII-2 is responsible for the synthesis of 4'-deoxyRSFs, such as chrysin and wogonin, wogonoside, baicalein, and baicalin, which are synthesized from chrysin. A gene encoding a cinnamic acid–specific coenzyme A ligase (SbCLL-7), which is highly expressed in roots, is required for the synthesis of RSFs by FNSII-2, as demonstrated by gene silencing. A specific isoform of chalcone synthase (SbCHS-2) that is highly expressed in roots producing RSFs is also required for the synthesis of chrysin. Our studies reveal a recently evolved pathway for biosynthesis of specific, bioactive 4'-deoxyflavones in the roots of S . baicalensis .
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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