TY - JOUR A1 - Koenig, Julian A1 - Abler, Birgit A1 - Agartz, Ingrid A1 - akerstedt, Torbjorn A1 - Andreassen, Ole A. A1 - Anthony, Mia A1 - Baer, Karl-Juergen A1 - Bertsch, Katja A1 - Brown, Rebecca C. A1 - Brunner, Romuald A1 - Carnevali, Luca A1 - Critchley, Hugo D. A1 - Cullen, Kathryn R. A1 - de Geus, Eco J. C. A1 - de la Cruz, Feliberto A1 - Dziobek, Isabel A1 - Ferger, Marc D. A1 - Fischer, Hakan A1 - Flor, Herta A1 - Gaebler, Michael A1 - Gianaros, Peter J. A1 - Giummarra, Melita J. A1 - Greening, Steven G. A1 - Guendelman, Simon A1 - Heathers, James A. J. A1 - Herpertz, Sabine C. A1 - Hu, Mandy X. A1 - Jentschke, Sebastian A1 - Kaess, Michael A1 - Kaufmann, Tobias A1 - Klimes-Dougan, Bonnie A1 - Koelsch, Stefan A1 - Krauch, Marlene A1 - Kumral, Deniz A1 - Lamers, Femke A1 - Lee, Tae-Ho A1 - Lekander, Mats A1 - Lin, Feng A1 - Lotze, Martin A1 - Makovac, Elena A1 - Mancini, Matteo A1 - Mancke, Falk A1 - Mansson, Kristoffer N. T. A1 - Manuck, Stephen B. A1 - Mather, Mara A1 - Meeten, Frances A1 - Min, Jungwon A1 - Mueller, Bryon A1 - Muench, Vera A1 - Nees, Frauke A1 - Nga, Lin A1 - Nilsonne, Gustav A1 - Ordonez Acuna, Daniela A1 - Osnes, Berge A1 - Ottaviani, Cristina A1 - Penninx, Brenda W. J. H. A1 - Ponzio, Allison A1 - Poudel, Govinda R. A1 - Reinelt, Janis A1 - Ren, Ping A1 - Sakaki, Michiko A1 - Schumann, Andy A1 - Sorensen, Lin A1 - Specht, Karsten A1 - Straub, Joana A1 - Tamm, Sandra A1 - Thai, Michelle A1 - Thayer, Julian F. A1 - Ubani, Benjamin A1 - van Der Mee, Denise J. A1 - van Velzen, Laura S. A1 - Ventura-Bort, Carlos A1 - Villringer, Arno A1 - Watson, David R. A1 - Wei, Luqing A1 - Wendt, Julia A1 - Schreiner, Melinda Westlund A1 - Westlye, Lars T. A1 - Weymar, Mathias A1 - Winkelmann, Tobias A1 - Wu, Guo-Rong A1 - Yoo, Hyun Joo A1 - Quintana, Daniel S. T1 - Cortical thickness and resting-state cardiac function across the lifespan BT - a cross-sectional pooled mega-analysis JF - Psychophysiology : journal of the Society for Psychophysiological Research N2 - Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12-87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS-or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research. KW - aging KW - autonomic nervous system KW - cortical thickness KW - heart rate KW - heart KW - rate variability KW - sex Y1 - 2020 U6 - https://doi.org/10.1111/psyp.13688 SN - 0048-5772 SN - 1469-8986 VL - 58 IS - 7 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Li, Chen A1 - Stoma, Svetlana A1 - Lotta, Luca A. A1 - Warner, Sophie A1 - Albrecht, Eva A1 - Allione, Alessandra A1 - Arp, Pascal P. A1 - Broer, Linda A1 - Buxton, Jessica L. A1 - Boeing, Heiner A1 - Langenberg, Claudia A1 - Codd, Veryan T1 - Genome-wide association analysis in humans links nucleotide metabolism to leukocyte telomere length JF - American Journal of Human Genetics N2 - Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease. KW - Mendelian randomization KW - risk KW - variants KW - disease KW - cancer KW - loci KW - database KW - genes KW - heart KW - gwas Y1 - 2019 VL - 106 IS - 3 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - John, Cathleen A1 - Grune, Jana A1 - Ott, Christiane A1 - Nowotny, Kerstin A1 - Deubel, Stefanie A1 - Kühne, Arne A1 - Schubert, Carola A1 - Kintscher, Ulrich A1 - Regitz-Zagrosek, Vera A1 - Grune, Tilman T1 - Sex Differences in Cardiac Mitochondria in the New Zealand Obese Mouse JF - Frontiers in Endocrinology N2 - Background: Obesity is a risk factor for diseases including type 2 diabetes mellitus (T2DM) and cardiovascular disorders. Diabetes itself contributes to cardiac damage. Thus, studying cardiovascular events and establishing therapeutic intervention in the period of type T2DM onset and manifestation are of highest importance. Mitochondrial dysfunction is one of the pathophysiological mechanisms leading to impaired cardiac function. Methods: An adequate animal model for studying pathophysiology of T2DM is the New Zealand Obese (NZO) mouse. These mice were maintained on a high-fat diet (HFD) without carbohydrates for 13 weeks followed by 4 week HFD with carbohydrates. NZO mice developed severe obesity and only male mice developed manifest T2DM. We determined cardiac phenotypes and mitochondrial function as well as cardiomyocyte signaling in this model. Results: The development of an obese phenotype and T2DM in male mice was accompanied by an impaired systolic function as judged by echocardiography and MyH6/7 expression. Moreover, the mitochondrial function only in male NZO hearts was significantly reduced and ERK1/2 and AMPK protein levels were altered. Conclusions: This is the first report demonstrating that the cardiac phenotype in male diabetic NZO mice is associated with impaired cardiac energy function and signaling events. KW - NZO KW - heart KW - obesity KW - mitochondrial function KW - echocardiography KW - systolic function Y1 - 2018 U6 - https://doi.org/10.3389/fendo.2018.00732 SN - 1664-2392 VL - 9 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Lombardo, Veronica A. A1 - Otten, Cecile A1 - Abdelilah-Seyfried, Salim T1 - Large-scale Zebrafish Embryonic Heart Dissection for Transcriptional Analysis JF - Journal of visualized experiments N2 - The zebrafish embryonic heart is composed of only a few hundred cells, representing only a small fraction of the entire embryo. Therefore, to prevent the cardiac transcriptome from being masked by the global embryonic transcriptome, it is necessary to collect sufficient numbers of hearts for further analyses. Furthermore, as zebrafish cardiac development proceeds rapidly, heart collection and RNA extraction methods need to be quick in order to ensure homogeneity of the samples. Here, we present a rapid manual dissection protocol for collecting functional/beating hearts from zebrafish embryos. This is an essential prerequisite for subsequent cardiac-specific RNA extraction to determine cardiac-specific gene expression levels by transcriptome analyses, such as quantitative real-time polymerase chain reaction (RT-qPCR). The method is based on differential adhesive properties of the zebrafish embryonic heart compared with other tissues; this allows for the rapid physical separation of cardiac from extracardiac tissue by a combination of fluidic shear force disruption, stepwise filtration and manual collection of transgenic fluorescently labeled hearts. KW - Developmental Biology KW - Issue 95 KW - zebrafish KW - embryo KW - heart KW - dissection KW - RNA KW - RT-qPCR Y1 - 2015 U6 - https://doi.org/10.3791/52087 SN - 1940-087X IS - 95 PB - JoVE CY - Cambridge ER - TY - JOUR A1 - Huber, Matthias A1 - Lezius, Susanne A1 - Reibis, Rona Katharina A1 - Treszl, Andras A1 - Kujawinska, Dorota A1 - Jakob, Stefanie A1 - Wegscheider, Karl A1 - Völler, Heinz A1 - Kreutz, Reinhold T1 - A Single Nucleotide Polymorphism near the CYP17A1 Gene Is Associated with Left Ventricular Mass in Hypertensive Patients under Pharmacotherapy JF - International journal of molecular sciences N2 - Cytochrome P450 17A1 (CYP17A1) catalyses the formation and metabolism of steroid hormones. They are involved in blood pressure (BP) regulation and in the pathogenesis of left ventricular hypertrophy. Therefore, altered function of CYP17A1 due to genetic variants may influence BP and left ventricular mass. Notably, genome wide association studies supported the role of this enzyme in BP control. Against this background, we investigated associations between single nucleotide polymorphisms (SNPs) in or nearby the CYP17A1 gene with BP and left ventricular mass in patients with arterial hypertension and associated cardiovascular organ damage treated according to guidelines. Patients (n = 1007, mean age 58.0 +/- 9.8 years, 83% men) with arterial hypertension and cardiac left ventricular ejection fraction (LVEF) 40% were enrolled in the study. Cardiac parameters of left ventricular mass, geometry and function were determined by echocardiography. The cohort comprised patients with coronary heart disease (n = 823; 81.7%) and myocardial infarction (n = 545; 54.1%) with a mean LVEF of 59.9% +/- 9.3%. The mean left ventricular mass index (LVMI) was 52.1 +/- 21.2 g/m(2.7) and 485 (48.2%) patients had left ventricular hypertrophy. There was no significant association of any investigated SNP (rs619824, rs743572, rs1004467, rs11191548, rs17115100) with mean 24 h systolic or diastolic BP. However, carriers of the rs11191548 C allele demonstrated a 7% increase in LVMI (95% CI: 1%-12%, p = 0.017) compared to non-carriers. The CYP17A1 polymorphism rs11191548 demonstrated a significant association with LVMI in patients with arterial hypertension and preserved LVEF. Thus, CYP17A1 may contribute to cardiac hypertrophy in this clinical condition. KW - clinical study KW - genetics KW - heart KW - hypertension KW - cytochrome P450 17A1 (Cyp17A1) Y1 - 2015 U6 - https://doi.org/10.3390/ijms160817456 SN - 1422-0067 VL - 16 IS - 8 SP - 17456 EP - 17468 PB - MDPI CY - Basel ER -