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Cardiovascular genomics: mechanisms & novel therapeutics - CVGen mech2ther

Grant number: 13/17368-0
Support type:Research Projects - Thematic Grants
Duration: February 01, 2014 - January 31, 2020
Field of knowledge:Health Sciences - Medicine
Principal Investigator:José Eduardo Krieger
Grantee:José Eduardo Krieger
Home Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Co-Principal Investigators:Alexandre da Costa Pereira
Assoc. researchers:Adriana Castello Costa Girardi ; Adriano Mesquita Alencar ; Ayumi Aurea Miyakawa Yamaguchi ; Luís Henrique Wolff Gowdak ; Marco Antonio Gutierrez ; Miriam Helena Fonseca-Alaniz ; Pedro Alexandre Favoretto Galante ; Pedro Alves Lemos Neto
Associated grant(s):16/50439-7 - A systems approach to identify and validate novel therapeutic targets to improve cardiac repair and regeneration following myocardial infarction, AP.R
Associated scholarship(s):18/20910-5 - Evaluation of phenotypic properties of micropatterned cardiac cells, BP.DR
17/13706-0 - Comprehensive T. cruzi and auto-antibody profiling in Chagas cardiomyopathy: leveraging phage-display and next-generation sequencing to reassess an old hypothesis, BP.PD
17/17296-0 - Mesenchymal stem cells-derived exosomes as paracrine effectors for cardioprotection after Acute Myocardial Infarction, BP.DR
+ associated scholarships 17/16910-7 - Monte Carlo modeling of transport processes in the cell membrane, BP.MS
17/05829-4 - Evaluation of the influence of fibroblasts on maturation and induction of cardiomyocytes with arrhythmogenic potential, BP.MS
17/07024-3 - Evaluation of cell therapy benefits based on smart copolymers combined to recombinant proteins after myocardial infarction in adult rats, BP.PD
17/05352-3 - Blood pressure control genes characterization and localization through the ENU methodology, BP.PD
16/23858-9 - Genetic analysis of patients with arrhythmogenic right ventricular dysplasia (ARVD) and functional characterization of differentiated cardiomyocytes (iPSC-CM), BP.DD
15/23445-3 - The association between chronic non-communicable diseases, race and genetic factors in Brazil: dissecting social disparities and biology in cardiovascular disease, BE.PQ
14/21646-9 - Characterization of living cells by Interometric techniques: speckle and Digital Holographic Microscopy, BP.PD
14/24577-8 - Nanostructures and iPSC derived cardiomyocytes approaches for cardiac protection and repair post-MI, BP.PD
14/14086-7 - Transplantation of pig iPSC-derived cardiac cells in a pig model of myocardial infarction, BP.PD
14/15256-3 - Spatial correlation between the presence of genetic variants in sarcomeric genes and hereditary cardiomyopathy: using next generation sequencing to reevaluate genotype and phenotype relationships, BP.PD
14/06844-9 - Endothelial to mesenchymal transition during vein arterialization remodeling: the role of mechanical stretch on endothelial plasticity, BP.DR
11/19678-1 - Cardiac progenitor cells identification and isolation using aptamers, BP.PD - associated scholarships

Abstract

Cardiovascular diseases (CVD) remain a major worldwide health problem and we propose an integrated Translational Approach that relies on genetic strategies to disassemble complex phenotypes and determination of the molecular underpinning of gene variants on cardiac and vascular phenotypes. The main goals of this proposal are to 1. Identify the molecular underpinning of cardiovascular diseases (CVD) or phenotypes and 2. Establish targeted therapeutics for CVDs. This will be accomplished by development of nine interconnected projects to address 1. The identification of genetic determinants of hypertension; 2. The mechanisms whereby physical forces (shear-stress and strain) influence vascular homeostasis and disease states; 3. Whether the adult cardiac regenerative capacity can be therapeutically modulated or replaced by a cell type approach to halt disease progression; and 4. How genetic variants do influence CV risk and outcomes. The proposal has a broad scope and shall catalyze incremental-type discoveries as well as high risk endeavors that may be translated into novel ways to predict events and to take preemptive steps to avoid irreversible damage or improve organ regeneration in cardiovascular medicine. (AU)

Scientific publications (26)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
VENTURINI, GABRIELA; MALAGRINO, PAMELLA ARAUJO; PADILHA, KALLYANDRA; TANAKA, LEONARDO YUJI; LAURINDO, FRANCISCO RAFAEL; DARIOLLI, RAFAEL; CARVALHO, VALDEMIR MELECHCO; MORAIS CARDOZO, KARINA HELENA; KRIEGER, JOSE EDUARDO; PEREIRA, ALEXANDRE DA COSTA. Integrated proteomics and metabolomics analysis reveals differential lipid metabolism in human umbilical vein endothelial cells under high and low shear stress. AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, v. 317, n. 2, p. C326-C338, AUG 2019. Web of Science Citations: 0.
TAPOROSKI, T. P.; DUARTE, N. E.; POMPEIA, S.; STERR, A.; GOMEZ, L. M.; ALVIM, R. O.; HORIMOTO, R. V. R.; KRIEGER, J. E.; VALLADA, H.; PEREIRA, A. C.; VON SCHANTZ, M.; NEGRAO, A. B. Heritability of semantic verbal fluency task using time-interval analysis. PLoS One, v. 14, n. 6 JUN 11 2019. Web of Science Citations: 0.
MIYAKAWA, AYUMI AUREA; BONIN, THAIZ FERRAZ; GASTALHO CAMPOS, LUCIENE CRISTINA; GIRAO-SILVA, THAIS; RIBEIRO-SILVA, JOAO CARLOS; OLIVEIRA DALLAN, LUIS ALBERTO; KRIEGER, JOSE EDUARDO. Activation of Interleukin-1 Beta in Arterialized Vein Grafts and the Influence of the -511C/T IL-1 beta Gene Polymorphism. JOURNAL OF CARDIOVASCULAR DEVELOPMENT AND DISEASE, v. 6, n. 2 JUN 2019. Web of Science Citations: 0.
GEOVANINI, GLAUCYLARA REIS; LORENZI-FILHO, GERALDO; DE PAULA, LILIAN K.; OLIVEIRA, CAMILA MACIEL; ALVIM, RAFAEL DE OLIVEIRA; BEIJAMINI, FELIPE; NEGRAO, ANDRE BROOKING; VON SCHANTZ, MALCOLM; KNUTSON, KRISTEN L.; KRIEGER, JOSE EDUARDO; PEREIRA, ALEXANDRE COSTA. Poor sleep quality and lipid profile in a rural cohort (The Baependi Heart Study). Sleep Medicine, v. 57, p. 30-35, MAY 2019. Web of Science Citations: 0.
ALKAN, E.; TAPOROSKI, T. P.; STERR, A.; VON SCHANTZ, M.; VALLADA, H.; KRIEGER, J. E.; PEREIRA, A. C.; ALVIM, R.; HORIMOTO, A. R. V. R.; POMPEIA, S.; NEGRAO, A. B.; EVANS, S. L. H. Metabolic syndrome alters relationships between cardiometabolic variables, cognition and white matter hyperintensity load. SCIENTIFIC REPORTS, v. 9, MAR 13 2019. Web of Science Citations: 0.
MIYAKAWA, AYUMI AUREA; BASSANEZE, VINICIUS; DUARTE, NUBIA ESTEBAN; GIRAO-SILVA, THAIS; BIZERRA, MONICA NUNES; CAMPOS, JULLIANA CARVALHO; KRIEGER, JOSE EDUARDO. Temporal Change of Extracellular Matrix during Vein Arterialization Remodeling in Rats. JOURNAL OF CARDIOVASCULAR DEVELOPMENT AND DISEASE, v. 6, n. 1 MAR 2019. Web of Science Citations: 0.
NADRUZ, WILSON; GIOLI-PEREIRA, LUCIANA; BERNARDEZ-PEREIRA, SABRINA; MARCONDES-BRAGA, FABIANA G.; FERNANDES-SILVA, MIGUEL M.; SILVESTRE, ODILSON M.; SPOSITO, ANDREI C.; RIBEIRO, ANTONIO L.; BACAL, FERNANDO; FERNANDES, FABIO; KRIEGER, JOSE E.; MANSUR, ALFREDO J.; PEREIRA, ALEXANDRE C. Temporal trends in the contribution of Chagas cardiomyopathy to mortality among patients with heart failure. HEART, v. 104, n. 18, p. 1522+, SEP 2018. Web of Science Citations: 3.
JENSEN, LEONARDO; NERI, ELIDA; BASSANEZE, VINICIUS; DE ALMEIDA OLIVEIRA, NATHALIA C.; DARIOLLI, RAFAEL; TURACA, LAURO T.; LEVY, DEBORA; VERONEZ, DOUGLAS; FERRAZ, MARIANA S. A.; ALENCAR, ADRIANO M.; BYDLOWSKI, SERGIO P.; CESTARI, IDAGENE A.; KRIEGER, JOSE EDUARDO. Integrated molecular, biochemical, and physiological assessment unravels key extraction method mediated influences on rat neonatal cardiomyocytes. Journal of Cellular Physiology, v. 233, n. 7, p. 5420-5430, JUL 2018. Web of Science Citations: 3.
KRIEGER, EDUARDO M.; DRAGER, LUCIANO F.; GIORGI, DANTE M. A.; PEREIRA, ALEXANDRE C.; SOARES BARRETO-FILHO, JOSE AUGUSTO; NOGUEIRA, ARMANDO R.; MILL, JOSE GERALDO; LOTUFO, PAULO A.; AMODEO, CELSO; BATISTA, MARCELO C.; BODANESE, LUIZ C.; CARVALHO, ANTONIO C. C.; CASTRO, IRAN; CHAVES, HILTON; COSTA, EDUARDO A. S.; FEITOSA, GILSON S.; FRANCO, ROBERTO J. S.; FUCHS, FLAVIO D.; GUIMARAES, ARMENIO C.; JARDIM, PAULO C.; MACHADO, CARLOS A.; MAGALHAES, MARIA E.; MION, JR., DECIO; NASCIMENTO, RAIMUNDO M.; NOBRE, FERNANDO; NOBREGA, ANTONIO C.; RIBEIRO, ANTONIO L. P.; RODRIGUES-SOBRINHO, CARLOS R.; SANJULIANI, ANTONIO F.; TEIXEIRA, MARIA DO CARMO B.; KRIEGER, JOSE E.; INVESTIGATORS, REHOT. Spironolactone Versus Clonidine as a Fourth-Drug Therapy for Resistant Hypertension: The ReHOT Randomized Study (Resistant Hypertension Optimal Treatment). Hypertension, v. 71, n. 4, p. 681-690, APR 2018. Web of Science Citations: 16.
GASTALHO CAMPOS, LUCIENE CRISTINA; RIBEIRO-SILVA, JOAO CARLOS; MENEGON, ALESSANDRA SANTOS; BARAUNA, VALERIO GARRONE; MIYAKAWA, AYUMI AUREA; KRIEGER, JOSE EDUARDO. Cyclic stretch-induced Crp3 sensitizes vascular smooth muscle cells to apoptosis during vein arterialization remodeling. Clinical Science, v. 132, n. 4, p. 449-459, FEB 28 2018. Web of Science Citations: 0.
MIYAKAWA, AYUMI A.; GIRAO-SILVA, THAIS; KRIEGER, JOSE E.; EDELMAN, ELAZER R. Rapamycin activates TGF receptor independently of its ligand: implications for endothelial dysfunction. Clinical Science, v. 132, n. 4, p. 437-447, FEB 28 2018. Web of Science Citations: 2.
FONSECA-ALANIZ, MIRIAM HELENA; HIGA, TALITA SAYURI; BEATRIZ FERRAZ-DE-CAMPOS, TARCILA; TAKADA, JULIE; LEONARDO TORRES-LEAL, FRANCISCO; SANT'ANNA EVANGELISTA, FABIANA; LIMA, FABIO BESSA; KRIEGER, JOSE EDUARDO. ACE-modulated adiposity is related to higher energy expenditure and independent of lipolysis and glucose incorporation into lipids in adipocytes. Physiological Genomics, v. 49, n. 12, p. 712-721, DEC 2017. Web of Science Citations: 1.
TEOFILO SATURI DE CARVALHO, ANA ELISA; BASSANEZE, VINICIUS; FORNI, MARIA FERNANDA; KEUSSEYAN, ALINE ALFONSO; KOWALTOWSKI, ALICIA JULIANA; KRIEGER, JOSE EDUARDO. Early Postnatal Cardiomyocyte Proliferation Requires High Oxidative Energy Metabolism. SCIENTIFIC REPORTS, v. 7, NOV 13 2017. Web of Science Citations: 6.
SILVA, PAMELA R. S.; JANNES, CINTHIA E.; OLIVEIRA, THEO G. M.; MINAME, MARCIO H.; ROCHA, VIVIANE Z.; CHACRA, ANA PAULA; GURGEL, MARIA HELANE C.; MONTENEGRO, RENAN M.; RODRIGUES SOBRINHO, CARLOS ROBERTO M.; BELLO MOREIRA, ANNIE SEIXAS; ASSAD, MARCELO H. V.; PINTO, MARINA R. C.; TADA, MAURICIO TERUO; SANTOS, RAUL D.; PEREIRA, ALEXANDRE C.; KRIEGER, JOSE E. Evaluation of clinical and laboratory parameters used in the identification of index cases for genetic screening of familial hypercholesterolemia in Brazil. ATHEROSCLEROSIS, v. 263, p. 257-262, AUG 2017. Web of Science Citations: 6.
DARIOLLI, RAFAEL; NAGHETINI, MARCUS V.; MARQUES, EUCLYDES F.; TAKIMURA, CELSO K.; JENSEN, LEONARDO S.; KIERS, BIANCA; TSUTSUI, JEANE M.; MATHIAS, JR., WILSON; LEMOS NETO, PEDRO A.; KRIEGER, JOSE E. Allogeneic pASC transplantation in humanized pigs attenuates cardiac remodeling post-myocardial infarction. PLoS One, v. 12, n. 4 APR 27 2017. Web of Science Citations: 3.
CARNEIRO, ANA PAULA; FONSECA-ALANIZ, MIRIAM HELENA; DALLAN, LUIS ALBERTO OLIVEIRA; MIYAKAWA, AYUMI AUREA; KRIEGER, JOSE EDUARDO. beta-arrestin is critical for early shear stress-induced Akt/eNOS activation in human vascular endothelial cells. Biochemical and Biophysical Research Communications, v. 483, n. 1, p. 75-81, JAN 29 2017. Web of Science Citations: 0.
MALAGRINO, PAMELLA ARAUJO; VENTURINI, GABRIELA; YOGI, PATRICIA SCHNEIDER; DARIOLLI, RAFAEL; PADILHA, KALLYANDRA; KIERS, BIANCA; GOIS, TAMIRIS CARNEIRO; MORAIS CARDOZO, KARINA HELENA; CARVALHO, VALDEMIR MELECHCO; SALGUEIRO, JESSICA SILVA; COSTA GIRARDI, ADRIANA CASTELLO; DE OLIVEIRA TITAN, SILVIA MARIA; KRIEGER, JOSE EDUARDO; PEREIRA, ALEXANDRE COSTA. Proteome analysis of acute kidney injury - Discovery of new predominantly renal candidates for biomarker of kidney disease. JOURNAL OF PROTEOMICS, v. 151, n. SI, p. 66-73, JAN 16 2017. Web of Science Citations: 5.
BEIJAMINI, F.; KNUTSON, K. L.; LORENZI-FILHO, G.; EGAN, K. J.; TAPOROSKI, T. P.; DE PAULA, L. K. G.; NEGRAO, A. B.; HORIMOTO, A. R. V. R.; DUARTE, N. E.; VALLADA, H.; KRIEGER, J. E.; PEDRAZZOLI, M.; PEREIRA, A. C.; VON SCHANTZ, M. Timing and quality of sleep in a rural Brazilian family-based cohort, the Baependi Heart Study. SCIENTIFIC REPORTS, v. 6, DEC 23 2016. Web of Science Citations: 9.
MALAGRINO, PAMELLA ARAUJO; VENTURINI, GABRIELA; YOGI, PATRICIA SCHNEIDER; DARIOLLI, RAFAEL; PADILHA, KALLYANDRA; KIERS, BIANCA; GOIS, TAMIRIS CARNEIRO; MOTTA-LEAL-FILHO, JOAQUIM MAURICIO; TAKIMURA, CELSO KIYOCHI; COSTA GIRARDI, ADRIANA CASTELLO; CARNEVALE, FRANCISCO CESAR; CANEVAROLO, RAFAEL; AVANCINI COSTA MALHEIROS, DENISE MARIA; DE MATTOS ZERI, ANA CAROLINA; KRIEGER, JOSE EDUARDO; PEREIRA, ALEXANDRE COSTA. Metabolomic characterization of renal ischemia and reperfusion in a swine model. Life Sciences, v. 156, p. 57-67, JUL 1 2016. Web of Science Citations: 6.
MARCHINI, JULIO F.; MIYAKAWA, AYUMI AUREA; TARASOUTCHI, FLAVIO; KRIEGER, JOSE EDUARDO; LEMOS, PEDRO; CROCE, KEVIN. Endothelial, platelet, and macrophage microparticle levels do not change acutely following transcatheter aortic valve replacement. JOURNAL OF NEGATIVE RESULTS IN BIOMEDICINE, v. 15, APR 11 2016. Web of Science Citations: 0.
EGAN, KIEREN J.; VON SCHANTZ, MALCOLM; NEGRAO, ANDRE B.; SANTOS, HADASSA C.; HORIMOTO, ANDREA R. V. R.; DUARTE, NUBIA E.; GONCALVES, GUILHERME C.; SOLER, JULIA M. P.; DE ANDRADE, MARIZA; LORENZI-FILHO, GERALDO; VALLADA, HOMERO; TAPOROSKI, TAMARA P.; PEDRAZZOLI, MARIO; AZAMBUJA, ANA P.; DE OLIVEIRA, CAMILA M.; ALVIM, RAFAEL O.; KRIEGER, JOSE E.; PEREIRA, ALEXANDRE C. Cohort profile: the Baependi Heart Study - a family-based, highly admixed cohort study in a rural Brazilian town. BMJ OPEN, v. 6, n. 10 2016. Web of Science Citations: 6.
KRENNING, GUIDO; BARAUNA, VALERIO G.; KRIEGER, JOSE E.; HARMSEN, MARTIN C.; MOONEN, JAN-RENIER A. J. Endothelial Plasticity: Shifting Phenotypes through Force Feedback. STEM CELLS INTERNATIONAL, 2016. Web of Science Citations: 21.
TAPOROSKI, TAMARA P.; NEGRAO, ANDRE B.; HORIMOTO, ANDREA R. V. R.; DUARTE, NUBIA E.; ALVIM, RAFAEL O.; DE OLIVEIRA, CAMILA M.; KRIEGER, JOSE E.; VON SCHANTZ, MALCOLM; VALLADA, HOMERO; PEREIRA, ALEXANDRE C. Shared Genetic Factors of Anxiety and Depression Symptoms in a Brazilian Family-Based Cohort, the Baependi Heart Study. PLoS One, v. 10, n. 12 DEC 9 2015. Web of Science Citations: 6.
VON SCHANTZ, MALCOLM; TAPOROSKI, TAMARA P.; HORIMOTO, ANDREA R. V. R.; DUARTE, NUBIA E.; VALLADA, HOMERO; KRIEGER, JOSE E.; PEDRAZZOLI, MARIO; NEGRAO, ANDRE B.; PEREIRA, ALEXANDRE C. Distribution and heritability of diurnal preference (chronotype) in a rural Brazilian family-based cohort, the Baependi study. SCIENTIFIC REPORTS, v. 5, MAR 18 2015. Web of Science Citations: 30.
AGUIAR, HELENA DE FAZIO; ROVEDA JUNIOR, ANTONIO CARLOS; PIVA, RENAN DE JESUS; ONODA, KEVIN AKIRA; MIYAKAWA, AYUMI AUREA; KRIEGER, JOSE EDUARDO; FRANCO, DOUGLAS WAGNER; TADINI, CARMEN CECILIA. Compatibility of Cassava Starch Films as Nitric Oxide Carrier for Potential Medical Device. Journal of Applied Polymer Science, v. 132, n. 2 JAN 10 2015. Web of Science Citations: 3.
BARAUNA, VALERIO G.; MANTUAN, PAMELA R.; MAGALHAES, FLAVIO C.; CAMPOS, LUCIENE C. G.; KRIEGEL, JOSE E. AT1 receptor blocker potentiates shear-stress induced nitric oxide production via modulation of eNOS phosphorylation of residues Thr(495) and Seri(1177). Biochemical and Biophysical Research Communications, v. 441, n. 4, p. 713-719, NOV 29 2013. Web of Science Citations: 21.

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