FRANCISCO RAFAEL MARTINS LAURINDO
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/64, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/64, Hospital das Clínicas, Faculdade de Medicina - Líder
15 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 15
- EXTRACELLULAR VESICLES AS PARACRINE REDOX REGULATORS OF THROMBOSIS AND HAEMOSTASIS(2023) GASPAR, Renato S.; LAURINDO, Francisco R. M.
- Analysing the impact of modifiable risk factors on cardiovascular disease mortality in Brazil(2022) GASPAR, Renato Simoes; REZENDE, Leandro F. M.; LAURINDO, Francisco Rafael MartinsObjectivesWe have examined the impact of changes in modifiable risk factors on CVD mortality in 26 Brazilian states from 2005 to 2017. MethodsData were acquired from the Global Burden of Diseases study (GBD) and official sources of the Brazilian government, totalling 312 state-year observations. Population attributable fractions (PAFs) were calculated to determine the number of deaths attributed to changes in each risk factor. Fixed-effects multivariable linear regression models were performed, adjusting for income, income inequality, poverty and access to healthcare. ResultsBetween 2005 and 2017, CVD deaths reduced by 21.42%, accompanied by a decrease in smoking (-33%) and increases in hyperglycaemia (+9.5%), obesity (+31%) and dyslipidaemia (+5.2%). Reduction in smoking prevented or postponed almost 20,000 CVD deaths in this period, while increased hyperglycaemia exposure resulted in more than 6,000 CVD deaths. The association between hyperglycaemia and CVD mortality was 5 to 10 times higher than those found for other risk factors, especially in women (11; 95%CI 7 to 14, deaths per 1-point increase in hyperglycaemia exposure). Importantly, the association between hyperglycaemia and CVD mortality was independent of socioeconomic status and access to healthcare, while associations for other risk factors after the same adjustments. ConclusionReduction in smoking was the risk factor that led to the highest number of CVD deaths prevented or postponed, while hyperglycaemia showed the most deleterious association with CVD mortality. Health policies should aim to directly reduce the prevalence of hyperglycaemia to mitigate the population burden of CVD in Brazil in the future.
conferenceObject Peri/epicellular protein disulfide isomerase PDI acts as an organizer of cytoskeletal mechanoadaptation in vascular smooth muscle cells(2018) TANAKA, Leonardo Yuji; ARAUJO, Thais Larissa; RODRIGUEZ, Andres Ignacio; FERRAZ, Mariana Sacrini Ayres; PELEGATI, Vitor Bianchin; SANTOS, Aline Mara; CESAR, Carlos Lens; ALENCAR, Adriano Mesquita; LAURINDO, Francisco Rafael Martins- Peri/epicellular Protein Disulfide Isomerase Reshapes Vascular Architecture to Counteracts Constrictive Remodeling(2014) TANAKA, Leonardo Yuji; ARAUJO, Haniel Alves; HIRONAKA, Gustavo Ken; ARAUJO, Thais Larissa; RODRIGUEZ, Andres Ignacio; CASAGRANDE, Annelise Silva; TAKIMURA, Celso Kiyoshi; LAURINDO, Francisco Rafael
- N-glycans as a tool to monitor subcellular Protein Disulfide Isomerase traffic(2023) OLIVEIRA, Percillia; TORRE, Marco Dalla; ORSI, Andrea; LAURINDO, Francisco R.; SITIA, Roberto
- A red wine intervention does not modify plasma trimethylamine N-oxide but is associated with broad shifts in the plasma metabolome and gut microbiota composition(2022) HAAS, Elisa A.; SAAD, Mario J. A.; SANTOS, Andrey; VITULO, Nicola; LEMOS JR., Wilson J. F.; MARTINS, Aline M. A.; PICOSSI, Carolina R. C.; FAVARATO, Desiderio; GASPAR, Renato S.; MAGRO, Daniela O.; LIBBY, Peter; LAURINDO, Francisco R. M.; LUZ, Protasio L. DaBackground Gut microbiota profiles are closely related to cardiovascular diseases through mechanisms that include the reported deleterious effects of metabolites, such as trimethylamine N-oxide (TMAO), which have been studied as diagnostic and therapeutic targets. Moderate red wine (RW) consumption is reportedly cardioprotective, possibly by affecting the gut microbiota. Objectives To investigate the effects of RW consumption on the gut microbiota, plasma TMAO, and the plasma metabolome in men with documented coronary artery disease (CAD) using a multiomics assessment in a crossover trial. Methods We conducted a randomized, crossover, controlled trial involving 42 men (average age, 60 y) with documented CAD comparing 3-wk RW consumption (250 mL/d, 5 d/wk) with an equal period of alcohol abstention, both preceded by a 2-wk washout period. The gut microbiota was analyzed via 16S rRNA high-throughput sequencing. Plasma TMAO was evaluated by LC-MS/MS. The plasma metabolome of 20 randomly selected participants was evaluated by ultra-high-performance LC-MS/MS. The effect of RW consumption was assessed by individual comparisons using paired tests during the abstention and RW periods. Results Plasma TMAO did not differ between RW intervention and alcohol abstention, and TMAO concentrations showed low intraindividual concordance over time, with an intraclass correlation coefficient of 0.049 during the control period. After RW consumption, there was significant remodeling of the gut microbiota, with a difference in beta diversity and predominance of Parasutterella, Ruminococcaceae, several Bacteroides species, and Prevotella. Plasma metabolomic analysis revealed significant changes in metabolites after RW consumption, consistent with improved redox homeostasis. Conclusions Modulation of the gut microbiota may contribute to the putative cardiovascular benefits of moderate RW consumption. The low intraindividual concordance of TMAO presents challenges regarding its role as a cardiovascular risk biomarker at the individual level. This study was registered at clinical trials.gov as NCT03232099.
- Protein Disulfide Isomerase-A1 (PDIA1) Remodels Endoplasmic Reticulum -Plasma Membrane Contact Sites: Possible Role of Nogo-B Protein Regulation(2022) BESSA, Tiphany De; OLIVEIRA, Percillia; DEBBAS, Victor; WOSNIAK JR., Joao; SANTOS, Celio; SHAH, Ajay; LAURINDO, Francisco R.
- Evidence for a protective role of Protein Disulfide Isomerase-A1 against aortic dissection(2023) PORTO, Fernando Garcez; TANAKA, Leonardo Yuji; BESSA, Tiphany Coralie de; OLIVEIRA, Percillia Victoria Santos; SOUZA, Julia Martins Felipe de; KAJIHARA, Daniela; FERNANDES, Carolina Goncalves; SANTOS, Patricia Nolasco; LAURINDO, Francisco Rafael MartinsBackground and aims: Redox signaling is involved in the pathophysiology of aortic aneurysm/dissection. Protein Disulfide Isomerases and its prototype PDIA1 are thiol redox chaperones mainly from endoplasmic reticulum (ER), while PDIA1 cell surface pool redox-regulates thrombosis, cytoskeleton remodeling and integrin activation, which are mechanisms involved in aortic disease. Here we investigate the roles of PDIA1 in aortic dissection. Methods: Initially, we assessed the outcome of aortic aneurysm/dissection in transgenic PDIA1-overexpressing FVB mice using a model of 28-day exposure to lysyl oxidase inhibitor BAPN plus angiotensin-II infusion. In a second protocol, we assessed the effects of PDIA1 inhibitor isoquercetin (IQ) against aortic dissection in C57BL/6 mice exposed to BAPN for 28 days. Results: Transgenic PDIA1 overexpression associated with ca. 50% (p = 0.022) decrease (vs.wild-type) in mor-tality due to abdominal aortic rupture and protected against elastic fiber breaks in thoracic aorta. Conversely, exposure of mice to IQ increased thoracic aorta dissection-related mortality rates, from ca. 18%-50% within 28-days (p = 0.019); elastic fiber disruption and collagen deposition were also enhanced. The structurally-related compound diosmetin, which does not inhibit PDI, had negligible effects. In parallel, stretch-tension curves indicated that IQ amplified a ductile-type of biomechanical failure vs. control or BAPN-exposed mice aortas. IQ-induced effects seemed unassociated with nonspecific antioxidant effects or ER stress. In both models, echo-cardiographic analysis of surviving mice suggested that aortic rupture was dissociated from progressive dilatation. Conclusions: Our data indicate a protective role of PDIA1 against aortic dissection/rupture and potentially un-covers a novel integrative mechanism coupling redox and biomechanical homeostasis in vascular remodeling.
- Protein Disulfide Isomerase overexpression induces mitochondrial reorganization and a differentiated VSMC phenotype: role of mitofusin-2(2023) WOSNIAK JR., Joao; RODRIGUES, Rafael F. G.; KAKIMOTO, Pamela A.; SILVA, Camille C. Caldeira da; ANTUNES, Fernanda; STRAUSS, Bryan E.; KOWALTOWSKI, Alicia; LAURINDO, Francisco R.
- Structural and functional characterization of the alternative splicing isoform P4HB-021 of the human protein disulfide isomerase-A1 (P4HB) gene(2023) KAJIHARA, Daniela; TEIXEIRA, Livia; LAURINDO, Francisco R.