JOSE EDUARDO KRIEGER
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Cardio-Pneumologia, Faculdade de Medicina - Docente
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/13 - Laboratório de Genética e Cardiologia Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/13 - Laboratório de Genética e Cardiologia Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
2 resultados
Resultados de Busca
Agora exibindo 1 - 2 de 2
- Multi-ancestry genome-wide gene-sleep interactions identify novel loci for blood pressure(2021) WANG, Heming; NOORDAM, Raymond; CADE, Brian E.; SCHWANDER, Karen; WINKLER, Thomas W.; LEE, Jiwon; SUNG, Yun Ju; BENTLEY, Amy R.; MANNING, Alisa K.; ASCHARD, Hugues; KILPELAINEN, Tuomas O.; ILKOV, Marjan; BROWN, Michael R.; HORIMOTO, Andrea R.; RICHARD, Melissa; BARTZ, Traci M.; VOJINOVIC, Dina; LIM, Elise; NIERENBERG, Jovia L.; LIU, Yongmei; CHITRALA, Kumaraswamynaidu; RANKINEN, Tuomo; MUSANI, Solomon K.; FRANCESCHINI, Nora; RAURAMAA, Rainer; ALVER, Maris; ZEE, Phyllis C.; HARRIS, Sarah E.; MOST, Peter J. van Der; NOLTE, Ilja M.; MUNROE, Patricia B.; PALMER, Nicholette D.; KUHNEL, Brigitte; WEISS, Stefan; WEN, Wanqing; HALL, Kelly A.; LYYTIKAINEN, Leo-Pekka; CONNELL, Jeff O.; EIRIKSDOTTIR, Gudny; LAUNER, Lenore J.; VRIES, Paul S. de; ARKING, Dan E.; CHEN, Han; BOERWINKLE, Eric; KRIEGER, Jose E.; SCHREINER, Pamela J.; SIDNEY, Stephen; SHIKANY, James M.; RICE, Kenneth; CHEN, Yii-Der Ida; GHARIB, Sina A.; BIS, Joshua C.; I, Annemarie Luik; IKRAM, M. Arfan; UITTERLINDEN, Andre G.; AMIN, Najaf; XU, Hanfei; LEVY, Daniel; HE, Jiang; LOHMAN, Kurt K.; ZONDERMAN, Alan B.; RICE, Treva K.; SIMS, Mario; WILSON, Gregory; SOFER, Tamar; RICH, Stephen S.; PALMAS, Walter; YAO, Jie; GUO, Xiuqing; I, Jerome Rotter; BIERMASZ, Nienke R.; MOOK-KANAMORI, Dennis O.; MARTIN, Lisa W.; BARAC, Ana; WALLACE, Robert B.; GOTTLIEB, Daniel J.; KOMULAINEN, Pirjo; HEIKKINEN, Sami; MAGI, Reedik; MILANI, Lili; METSPALU, Andres; STARR, John M.; MILANESCHI, Yuri; WAKEN, R. J.; GAO, Chuan; WALDENBERGER, Melanie; PETERS, Annette; STRAUCH, Konstantin; MEITINGER, Thomas; ROENNEBERG, Till; VOLKER, Uwe; DORR, Marcus; SHU, Xiao-Ou; MUKHERJEE, Sutapa; HILLMAN, David R.; KAHONEN, Mika; WAGENKNECHT, Lynne E.; GIEGER, Christian; GRABE, Hans J.; ZHENG, Wei; PALMER, Lyle J.; LEHTIMAKI, Terho; GUDNASON, Vilmundur; MORRISON, Alanna C.; PEREIRA, Alexandre C.; FORNAGE, Myriam; PSATY, Bruce M.; DUIJN, Cornelia M. van; LIU, Ching-Ti; KELLY, Tanika N.; EVANS, Michele K.; BOUCHARD, Claude; FOX, Ervin R.; KOOPERBERG, Charles; ZHU, Xiaofeng; LAKKA, Timo A.; ESKO, Tonu; NORTH, Kari E.; DEARY, Ian J.; SNIEDER, Harold; PENNINX, Brenda W. J. H.; GAUDERMAN, W. James; RAO, Dabeeru C.; REDLINE, Susan; HEEMST, Diana vanLong and short sleep duration are associated with elevated blood pressure (BP), possibly through effects on molecular pathways that influence neuroendocrine and vascular systems. To gain new insights into the genetic basis of sleep-related BP variation, we performed genome-wide gene by short or long sleep duration interaction analyses on four BP traits (systolic BP, diastolic BP, mean arterial pressure, and pulse pressure) across five ancestry groups in two stages using 2 degree of freedom (df) joint test followed by 1df test of interaction effects. Primary multi-ancestry analysis in 62,969 individuals in stage 1 identified three novel gene by sleep interactions that were replicated in an additional 59,296 individuals in stage 2 (stage 1 + 2 P-joint < 5 x 10(-8)), including rs7955964 (FIGNL2/ANKRD33) that increases BP among long sleepers, and rs73493041 (SNORA26/C9orf170) and rs10406644 (KCTD15/LSM14A) that increase BP among short sleepers (P-int < 5 x 10(-8)). Secondary ancestry-specific analysis identified another novel gene by long sleep interaction at rs111887471 (TRPC3/KIAA1109) in individuals of African ancestry (P-int = 2 x 10(-6)). Combined stage 1 and 2 analyses additionally identified significant gene by long sleep interactions at 10 loci including MKLN1 and RGL3/ELAVL3 previously associated with BP, and significant gene by short sleep interactions at 10 loci including C2orf43 previously associated with BP (P-int < 10(-3)). 2df test also identified novel loci for BP after modeling sleep that has known functions in sleep-wake regulation, nervous and cardiometabolic systems. This study indicates that sleep and primary mechanisms regulating BP may interact to elevate BP level, suggesting novel insights into sleep-related BP regulation.
- Sex differences in the lung ACE/ACE2 balance in hypertensive rats(2021) MARTINS, Flavia L.; TAVARES, Caio A. M.; MALAGRINO, Pamella A.; RENTZ, Thiago; BENETTI, Acaris; RIOS, Thiago M. S.; PEREIRA, Gabriel M. D.; CARAMELLI, Bruno; TEIXEIRA, Samantha K.; KRIEGER, Jose E.; GIRARDI, Adriana C. C.The angiotensin-converting enzyme (ACE)/Angiotensin II (Ang II) and angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1-7) (Ang-(1-7)) pathways are coexpressed in most tissues. The balance between these pathways determines, at least in part, whether tissue damage will occur in response to pathological stimuli. The present study tested the hypothesis that male sex and high blood pressure are associated with ACE/ACE2 imbalance in the lungs. Experiments were conducted in male and female Wistar rats and spontaneously hypertensive rats (SHRs). Lung ACE and ACE2 gene expression was also evaluated in normotensive and hypertensive humans using the Genotype-Tissue Expression (GTEx) project. Compared with Wistar rats and female SHRs, male SHRs displayed reduced lung ACE2 mRNA, ACE2 protein abundance and ACE2 activity, and increased Ang II concentration. Lung ACE mRNA levels were higher in male SHRs than in Wistar rats, whereas lung ACE protein abundance and activity were similar among the four groups of rats. Lung Ang-(1-7) concentration was higher in female than in male SHRs (89 +/- 17 vs. 43 +/- 2 pg/g, P<0.05). Lung ACE to ACE2 mRNA expression in hypertensive patients was significantly higher than that in normotensive subjects. Taken together, these results demonstrate that male hypertensive rats display imbalance between the ACE/Ang II and ACE2/Ang-(1-7) pathways in the lungs mainly attributable to ACE2 down-regulation. Further studies should be conducted to investigate whether this imbalance between ACE/ACE2 may promote and accelerate lung injury in respiratory infections, including coronavirus disease 2019 (COVID-19).