Farmacologia Cardiovascular e Metabólica

O nosso grupo tem uma tradição de investigação nos efeitos cardiovasculares associados à hypóxia e stress oxidativo, nomeadamente na hipertensão.

Utiliza essencialmente, abordagens fenotípicas num perspectiva centrada no fármaco e na medicina de precisão: novos alvos terapêuticos, novos fármacos, variabilidade na resposta aos fármacos (gender differences) e reações adversas medicamentosas.

As abordagens fenotípicas incluem, alterações cardiometabólicas e parâmetros de risco cardiovascular, indicadores de função tubular renal, indicadores de actividades enzimática e alterações redox (eg. sulfotransferases, uNaC, tioloma, indoleamina, 2,3-dioxigenase), em modelos animais in vivo (eg. hipóxia crónica intermitente) e em estudos clínicos (eg. apneia obstrutiva do sono, hipertensão, doença renal crónica, HIV).

Mais recentemente tem vindo a interessar-se particularmente pela associação entre fatores de risco cardiovascular e a exposição ambiental através do recetor AhR (aryl hydrocarbon receptor).

Graphical Abstract

1. PtCRIN 

An infrastructure dedicated to improve national clinical research by promoting a more efficient implementation of clinical trials and particularly international cooperation. Multinational clinical trials provide the evidence necessary to approve new drugs and medical devices but require complex technical competences. PtCRIN implemented a network of academic clinical trial units (CTUs) in Portugal to deal with these requirements and linked to European counterparts (ECRIN-ERIC).

Clinical experimental studies (trials) provide the highest level of evidence to support the approval of innovative health technologies (drugs, cell therapies, devices, food, behaviour). Experimental studies require 2 types of infrastructures: clinical sites (CRC) that manage the patients and implement the studies, and clinical trial units (CTUs or CROs) that manage the whole study from the design, funding, regulatory approvals, implementation, monitoring, publication, etc. PtCRIN created at the national level the concept of CTUs that provide services at not-for-profit rates to public sponsors and SMEs.

PtCRIN is a consortium of 10 national R&D institutions that host CTUs providing general services for clinical studies or equivalent units limited to the provision of specific services (statistics, informatics). The consortium has been already working in close articulation with an additional 11 affiliated health care units but is open to all.

PtCRIN's CTUs follow the standards/certification of the counterpart European infrastructure (ECRIN-ERIC) promoting the capture of international funds, fostering international cooperation and making Europe a single area for clinical research.

PtCRIN privileges investigator independent clinical trials (IICTs) across all disease. These trials provide an unbiased assessment of preventive, diagnostic and therapeutic interventions that might not otherwise be investigated and are relevant to policymakers and to real-world clinical practice.

2. AhR-CYP1A:1 linking environmental exposure and sleep apnea to improve arterial hypertension management (PTDC/MED-TOX/30418/2017)

 

graphical absract

Investigador Principal:

  • 2021-2024 Muscle up with intermittent hypoxia: a matter of intensity, gender and metabolism. iNOVA4Health- IUDB/004462/2020/TL2/P2
  • 2019 - 2020 (EudraCT 2019-002266-12 and CEIC 20191098): “Variability of 1A1 sulfotransferase activity in humans: an approach to predict drug response - 2nd part: Analysis of inter-individual variability in hypertensive patients.”, Hospital da Luz Lisboa, Portugal
  • 2018 - 2021 (PTDC/MED-TOX/30418/2017): “AhR-CYP1A:1 linking environmental exposure and sleep apnea to improve arterial hypertension management.”, Fundação para a Ciência e a Tecnologia, Portugal
  • 2017 - 2019 (iN4H_201707-05-30): “Efficacy of olive oil and phenolic compounds in reversing hypertension induced by chronic intermittent hypoxia.”, iNOVA4Health, Portugal
  • 2016 - 2019 (UID/Multi/04462/2013 iN4H_201601-02-021): “(per)Sulfidomics: benchmarking mechanisms underlying drug toxicity and drug resistance in precision medicine.”, Fundação para a Ciência e a Tecnologia
  • 2016 - 2019 (PAULIF): “AhR: a therapeutic target for co-morbidities associated with chronic intermittent hypoxia.”, Governo da República Portuguesa Ministério da Ciência Tecnologia e Ensino Superior, Portugal and Gouvernement Francais Ministère de l'Enseignement supérieur de la Recherche et de l'Innovation, France
  • 2016 - 2019 (Protocol nº HLUZ_001_2016; EudraCT nº: 2016-001395-29): “Variability of sulfotransferase 1A1 activity in humans: an approach to improve predictive drug response? Part I: Analysis of intraindividual variation in healthy adults.”, Hospital da Luz Lisboa, Portugal
  • 2016 - 2017 (PGG/032/2015): “Kidney tubular lesion in HIV patients.”, Gilead Sciences Lda, Portugal
  • 2014 - 2022 (2013/713/EU): “Portuguese Clinical Research Infrastructures network (PtCRIN).”, Fundação para a Ciência e a Tecnologia, Portugal
  • 2014 - 2015 (EXPL/DTP-FTO/1792/2013): “HivKIomics - new insights on tubular injury and nephrotoxicity diagnosis and prediction in HIV-infected patients .”, Fundação para a Ciência e a Tecnologia, Portugal
  • 2013 - 2015 (EXPL/DTP-PIC/1758/2013): “HIV nefromics: new markers of nephrotoxicity induced by antiretrovirals in hiv+ patients.” , Sociedade Portuguesa de Nefrologia, Portugal)
  • 2013 - 2014 (EXPL/DTP-FTO/0204/2012): “TeachIng an olD drug nEw tricks: re-profiling An anti-HIV drug as an HDL modulator.”, Fundação para a Ciência e a Tecnologia, Portugal
  • 2012 - 2015 (FCG121986): “Zebrafish as a biomedical tool to evaluate drug toxicity.”, Fundação Calouste Gulbenkian. Portugal
  • 2011 - 2014 (PTDC/SAU-TOX/111663/2009): “Hepatic toxicity in HIV-infected individuals exposed to nevirapine.”, Fundação para a Ciência e a Tecnologia, Portugal
  • 2011 - 2014 (PTDC/SAUTOX/112264/2009): “Chronic Intermitent Eucapnic Hypoxia: systemic effects and evaluation of antihypertensive drugs efficacy.”, Fundação para a Ciência e a Tecnologia, Portugal

Membro da Equipa:

  • 2018 - 2021 (PTDC/NAN-OPT/31311/2017): “Photonic biosensor for point of care and early diagnostics of acute kidney injury.”, Fundação para a Ciência e a Tecnologia, Portugal
  • 2013 - 2016 (RECI/QEQ-MED/0330/2012): “From small bioactive molecules to an integrated OMICS approach: Mass Spectrometry tools for mechanistic insights into drug-like and functional properties, toxicity, and stress responses.”, Fundação para a Ciência e a Tecnologia, Portugal
  • 2014 - 2015 (EXPL/DTP-PIC/1758/2013): “Point of care testing of cardiovascular disease markers - detection of homocystein-thiolactone.”, Fundação para a Ciência e a Tecnologia, Portugal
  • 2010 - 2013 (PTDC/QUI-QUI/113910/2009): “Bioactivation routes of the anti - HIV drug Nevirapine: identification of reactive metabolites and mutagenic potential.”, Fundação para a Ciência e a Tecnologia, Portugal

Internacional:

- Xavier Coumol & Robert Barouki INSERM UMR-S 1124, Toxicologie Pharmacologie et Signalisation Cellulaire & France, Université Paris Descartes, Sorbonne Paris Cité
- Oleg A. Mayoboroda - Leiden University Medical Centre, Leiden, The Netherlands
- Demotes, ECRIN

Nacional:

- Alexandra Antunes & Matilde Marques - Instituto Superior Técnico
- Jacinta Serpa - IPO Lisboa
- Joana Miranda - FFUL
- Rosário Bronze - IBET
- Alessandro Fantoni - ISEL
- João Vicente - ITQB
- Gabriela Almeida - Egas Moniz
- Teresa Branco e Karina Soto Hospital Fernando da Fonseca, Amadora
- Anabela Raimundo, Hospital da LUZ
- Manuel Almeida e Patricia Branco, CHLO
-Margarida Aguiar, HBA
-Alexandra Mineiro, CHULC
- Inês Alves da ANDO/EUPATI

Investigador Principal

Sofia de Azeredo Pereira

Equipa

Maria Emília Monteiro
Senior Investigator
Judit Morello
Investigator
Clara Matos
Clinical Researcher, MD
Natália Marto
Clinical Researcher, MD
Cátia Moreira de Sousa
Luísa Santos
António Junior
Post-Doctoral Researcher
António Pimpão
PhD Student
Maria João Correia
PhD Student
Catarina Sequeira
Facility Manager
Ana Rita Sequeira
MSc Student
Rafaela Madaleno Pedro
Undergraduated Student
Teresa Eloy Pires
Undergraduated Student