Endothelial dysfunction in hypertensive disorders of pregnancy

• Grant number: 21/12010-7
• Support Opportunities: Research Projects - Thematic Grants
• Start date: June 01, 2023
• End date: May 31, 2028
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Valeria Cristina Sandrim
• Grantee: Valeria Cristina Sandrim
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• City of the host institution: Botucatu
• Principal investigators: Carlos Alan Candido Dias Junior ; Ricardo de Carvalho Cavalli
• Associated researchers: Allan Felipe Fattori Alves ; Ana Carolina Taveiros Palei ; Arielle Cristina Arena ; Daniela Alves Pereira ; Fernando Barbosa Júnior ; Jose Carlos Peraçoli ; Jose Eduardo Tanus dos Santos ; Marcelo Rizzatti Luizon ; Margarida Sâncio da Cruz Fardilha ; Maria Fernanda Hornos Carneiro ; Mariane Bertagnolli ; Mattias Carlström ; Montenegro MF ; Patrícia Nessralla Alpoim ; Priscila Rezeck Nunes ; Subian Ananth Karumanchi
• Associated research grant(s): 25/13946-7 - Use of Aspirin for Preeclampsia Prevention in Pregnant Women with Chronic Hypertension: A Retrospective Analysis of a Tertiary Hospital in Brazil, AP.R; 25/13875-2 - Endothelial dysfunction in preeclampsia: use of the explant model as an alternative for drug studies, AP.R; 24/01935-8 - Endothelial dysfunction in preeclampsia: evaluation of potential new drugs in an in vitro model, AP.R
• Associated scholarship(s): 25/18416-6 - Endothelial dysfunction in pre-eclampsia: potential drugs and new pharmacological targets obtained from "omics" tools, BP.PD; 25/01623-9 - Analysis of Endothelial Dysfunction and Inflammatory Markers in Chronic Hypertensive Pregnant Women Supplemented with Beetroot Extract, BP.TT; 23/12666-5 - Characterization of the clinical profile of normotensive and preeclamptic patients for the study of the relationship between endocrine disruptors and preeclampsia, BP.IC; + associated scholarships 23/11925-7 - Endothelial dysfunction in preeclampsia: potential drugs and new pharmacological targets obtained from of "omics" tools, BP.PD; 23/07589-1 - Blood pressure control in chronic hypertensive pregnant women with beet juice supplementation from the 2nd trimester (BEET_CH), BP.PD; 23/06195-0 - Evaluation of endothelial dysfunction in experimental model of preeclampsia-like symptoms induced by reduction of uterine perfusion pressure (RUPP) in pregnant rats, BP.DD; 23/06651-5 - Study of endocrine disruptors (EDRs) and sex hormones in PE., BP.PD - associated scholarships

Abstract

It is likely that the Endothelial Dysfunction (ED) found in Hypertensive Disorders of Pregnancy (HDP) are evoked by the actions of multiple factors and several pathways. Then the discovery and the understanding of these converging pathways that contribute to ED and poor outcome of pregnancy can addressing potential molecules with are modulated by different drugs. The use of omics tools, such as transcriptome and proteome, may help in this field. Importantly, although the knowledge of ED in HDP and the mechanisms underlying these processes are now becoming increasingly understood, this is not corresponding to developments in drug development/uses. There are no investments of pharmacy industries in this field due probably to high-risk investment in pregnant treatment. Moreover, even with improvement in researches on the pathophysiology of gestational hypertensive diseases, drug therapy remains limited and, therefore, is a contributing factor to the maintenance of high rates of maternal mortality. Therefore, the current proposal will explore ED in HDP. We have divided it into five subprojects:SP1 - Endothelial dysfunction in pre-eclampsia: potential drugs and new pharmacological targets obtained from "omics" toolsSP2 - Blood pressure control in chronic hypertensive pregnant women with beetroot juice supplementation starting in the 2nd trimester (BEET_CH)SP3 - Evaluation of endothelial dysfunction in experimental model of preeclampsia-like symptoms induced by reduction of uterine perfusion pressure (RUPP) in pregnant ratsSP 4- Study of endocrine disruptors and sex hormones in PE (EDRs)SP 5 - Biomarkers and pharmacogenetics of antihypertensive therapy in preeclampsia. (AU)

Scientific publications

(14)

(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)

DOS SANTOS, CAMILA MACIEL; GONCALVES, PALOMA LETICIA; DE OLIVEIRA, TAMARA ANASTACIO; TEIXEIRA, CLECIA DIAS; BARBOSA, PRISCILA OLIVEIRA; DA SILVA, RAFAELA ROSA; PEDRO, CAROL CONSTANTINO; BREGUEZ, GUSTAVO SILVEIRA; DE SOUZA, MELINA OLIVEIRA. Daily supplementation with guarana powder (Paullinia cupana) modifies short-chain fatty acid concentration and reduces total cholesterol and serum glucose in young rats. NUTRIRE, v. 50, n. 1, p. 10-pg., 2025-04-04. (23/07589-1, 21/12010-7)

JORGE, BARBARA CAMPOS; DA SILVA, JULIA POLOTTO; DOS SANTOS, SARA TAWANY CAETANO; BARBOSA, FERNANDO; SANDRIM, VALERIA CRISTINA; ARENA, ARIELLE CRISTINA. Potential role of endocrine-disrupting chemicals in preeclampsia: A hypothesis based on integration of epidemiological and experimental evidence. REPRODUCTIVE TOXICOLOGY, v. 137, p. 12-pg., 2025-10-01. (21/12010-7, 23/06651-5, 23/12666-5, 24/06672-5)

TALLARICO, GUSTAVO MOLEIRO; BARBOSA, PRISCILA OLIVEIRA; LIMA JR, LUIZ SERGIO; CAVALLI, RICARDO CARVALHO. Early preeclampsia is associated with persistence of hypertension 3 months postpartum in women: an observational study at a tertiary hospital in Brazil. Revista Brasileira de Ginecologia e Obstetrícia, v. 47, p. 5-pg., 2025-01-01. (23/07589-1, 21/12010-7)

PINTO-SOUZA, CAROLINE C.; KAIHARA, JULYANE N. S.; NUNES, PRISCILA R.; MASTELLA, MOISES H.; ROSSINI, BRUNO C.; CAVECCI-MENDONCA, BRUNA; CAVALLI, RICARDO DE CARVALHO; DOS SANTOS, LUCILENE D.; SANDRIM, VALERIA C.. Different Proteomic Profiles Regarding Antihypertensive Therapy in Preeclampsia Pregnant. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 25, n. 16, p. 16-pg., 2024-08-01. (22/07605-4, 23/11925-7, 21/12010-7, 23/08897-1)

PINTO-SOUZA, CAROLINE CRISTINA; KAIHARA, JULYANE NATSUMI SAITO; ROSSINI, BRUNO CESAR; CAVALLI, RICARDO DE CARVALHO; DOS SANTOS, LUCILENE DELAZARI; SANDRIM, VALERIA CRISTINA. Pathophysiological mechanisms in severe preeclampsia: role of upregulated proteins in blood pressure, extracellular matrix and immunity. Revista Brasileira de Ginecologia e Obstetrícia, v. 47, p. 11-pg., 2025-01-01. (22/07605-4, 21/12010-7)

PEREIRA, DANIELA ALVES; LUIZON, MARCELO RIZZATTI; CAVALLI, RICARDO CARVALHO; TANUS-SANTOS, JOSE EDUARDO; SANDRIM, VALERIA CRISTINA. Functional MPO Polymorphisms and Haplotypes Affect Both Myeloperoxidase Levels and Association with Hypertensive Disorders of Pregnancy. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 26, n. 15, p. 10-pg., 2025-07-23. (21/12010-7)

VIANA-MATTIOLI, SARAH; FONSECA-ALANIZ, MIRIAM HELENA; PINHEIRO-DE-SOUSA, IGUARACY; ROSA JUNIOR, RICARDO; MASTELLA, MOISES HENRIQUE; CAVALLI, RICARDO DE CARVALHO; SANDRIM, VALERIA CRISTINA. Plasma from hypertensive pregnancy patients induce endothelial dysfunction even under atheroprotective shear stress. SCIENTIFIC REPORTS, v. 15, n. 1, p. 15-pg., 2025-02-08. (21/12010-7, 23/11925-7, 19/07230-8)

NUNES, PRISCILA R.; BRUDER, RICARDO M.; KAIHARA, JULYANE N. S.; DE MORAES, FABIO R.; TASIC, LJUBICA; BERNARDINO, RAQUEL L.; BRAGA, PATRICIA; OLIVEIRA, PEDRO F.; REBELO, IRENE; FARDILHA, MARGARIDA; et al. Endothelial responses to angiogenic modulators highlight metabolic mechanisms underlying vascular dysfunction in preeclampsia. Placenta, v. 171, p. 10-pg., 2025-11-01. (21/12010-7, 18/24069-3, 23/08897-1, 22/07226-3)

KAIHARA, JULYANE N. S.; DE MORAES, FABIO ROGERIO; NUNES, PRISCILA REZECK; ALVES, MARCO G.; CAVALLI, RICARDO C.; TASIC, LJUBICA; SANDRIM, VALERIA CRISTINA. Plasma metabolic profile reveals signatures of maternal health during gestational hypertension and preeclampsia without and with severe features. PLoS One, v. 19, n. 11, p. 22-pg., 2024-11-26. (23/08897-1, 18/24069-3, 19/07230-8, 21/12010-7)

VIANA-MATTIOLI, SARAH; FONSECA-ALANIZ, MIRIAM HELENA; PINHEIRO-DE-SOUSA, IGUARACY; KRIEGER, JOSE EDUARDO; SANDRIM, VALERIA CRISTINA. Missi ng links in preeclampsia cell model systems of endothelial dysfunction. TRENDS IN MOLECULAR MEDICINE, v. 29, n. 7, p. 13-pg., 2023-07-01. (19/07230-8, 21/12010-7)

RODRIGUES, SERGINARA DAVID; DA SILVA, MARIA LUIZA SANTOS; MARTINS, LAISLA ZANETONI; GOMES, SASKIA ESTELA BIASOTTI; MARIANI, NOEMIA A. P.; SILVA, ERICK J. R.; KUSHIMA, HELIO; MATTOS, BRUNA RAHAL; RIZZI, ELEN; DIAS-JUNIOR, CARLOS ALAN. Pregnancy hypertension-associated endothelial dysfunction is attenuated by isoflurane anesthesia: Evidence of protective effect related to increases in nitric oxide. Life Sciences, v. 331, p. 13-pg., 2023-10-15. (21/12010-7, 20/03135-8, 22/10773-6, 21/03792-1, 21/08380-3)

MARTINS, LAISLA ZANETONI; DA SILVA, MARIA LUIZA SANTOS; RODRIGUES, SERGINARA DAVID; GOMES, SASKIA ESTELA BIASOTTI; MOLEZINI, LAURA; RIZZI, ELEN; MONTENEGRO, MARCELO FREITAS; DIAS-JUNIOR, CARLOS ALAN. Sodium Nitrite Attenuates Reduced Activity of Vascular Matrix Metalloproteinase-2 and Vascular Hyper-Reactivity and Increased Systolic Blood Pressure Induced by the Placental Ischemia Model of Preeclampsia in Anesthetized Rats. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 24, n. 16, p. 16-pg., 2023-08-01. (21/12010-7, 20/03135-8, 22/10773-6, 21/03792-1, 21/08380-3)

PEREIRA, DANIELA A.; DE CASTRO, RICARDO N. F.; PALEI, ANA C.; CAVALLI, RICARDO C.; SANDRIM, VALERIA C.; LUIZON, MARCELO R.. ADIPOQ genotypes and haplotypes, circulating adiponectin levels and responsiveness to antihypertensive therapy in preeclampsia. PHARMACOGENOMICS, v. N/A, p. 10-pg., 2025-10-13. (19/07230-8, 21/12010-7)

NUNES, PRISCILA R.; OLIVEIRA, PEDRO F.; REBELO, IRENE; SANDRIM, VALERIA C.; ALVES, MARCO G.. Relevance of real-time analyzers to determine mitochondrial quality in endothelial cells and oxidative stress in preeclampsia. VASCULAR PHARMACOLOGY, v. 155, p. 12-pg., 2024-04-09. (22/07226-3, 21/12010-7)