PAMELLA ARAUJO MALAGRINO
Projetos de Pesquisa
Unidades Organizacionais
LIM/13 - Laboratório de Genética e Cardiologia Molecular, Hospital das Clínicas, Faculdade de Medicina
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- Potential Biomarkers of the Turnover, Mineralization, and Volume Classification: Results Using NMR Metabolomics in Hemodialysis Patients(2020) BAPTISTA, A.L.; PADILHA, K.; MALAGRINO, P.A.; VENTURINI, G.; ZERI, A.C.M.; REIS, L.M. dos; MARTINS, J.S.; JORGETTI, V.; PEREIRA, A.C.; TITAN, S.M.; MOYSES, R.M.A.Bone biopsy is still the gold standard to assess bone turnover (T), mineralization (M), and volume (V) in CKD patients, and serum biomarkers are not able to replace histomorphometry. Recently, metabolomics has emerged as a new technique that could allow for the identification of new biomarkers useful for disease diagnosis or for the understanding of pathophysiologic mechanisms, but it has never been assessed in the chronic kidney disease–mineral and bone disorder (CKD–MBD) scenario. In this study, we investigated the association between serum metabolites and the bone TMV classification in patients with end-stage renal disease by using serum NMR spectroscopy and bone biopsy of 49 hemodialysis patients from a single center in Brazil. High T was identified in 21 patients and was associated with higher levels of dimethylsulfone, glycine, citrate, and N-acetylornithine. The receiver-operating characteristic curve for the combination of PTH and these metabolites provided an area under the receiver-operating characteristic curve (AUC) of 0.86 (0.76 to 0.97). Abnormal M was identified in 30 patients and was associated with lower ethanol. The AUC for age, diabetes mellitus, and ethanol was 0.83 (0.71 to 0.96). Low V was identified in 17 patients and was associated with lower carnitine. The association of age, phosphate, and carnitine provided an AUC of 0.83 (0.70 to 0.96). Although differences among the curves by adding selected metabolites to traditional models were not statistically significant, the accuracy of the diagnosis according to the TMV classification seemed to be improved. This is the first study to evaluate the TMV classification system in relation to the serum metabolome assessed by NMR spectroscopy, showing that selected metabolites may help in the evaluation of bone phenotypes in CKD–MBD. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
- Proteome analysis of acute kidney injury - Discovery of new predominantly renal candidates for biomarker of kidney disease(2017) MALAGRINO, Pamella Araujo; VENTURINI, Gabriela; YOGI, Patricia Schneider; DARIOLLI, Rafael; PADILHA, Kallyandra; KIERS, Bianca; GOIS, Tamiris Carneiro; CARDOZO, Karina Helena Morais; CARVALHO, Valdemir Melechco; SALGUEIRO, Jessica Silva; GIRARDI, Adriana Castello Costa; TITAN, Silvia Maria de Oliveira; KRIEGER, Jose Eduardo; PEREIRA, Alexandre CostaThe main bottleneck in studies aiming to identify novel biomarkers in acute kidney injury (AKI) has been the identification of markers that are organ and process specific. Here, we have used different tissues from a controlled porcine renal ischemia/reperfusion (I/R) model to identify new, predominantly renal biomarker candidates for kidney disease. Urine and serum samples were analyzed in pre-ischemia, ischemia (60 min) and 4, 11 and 16 h post-reperfusion, and renal cortex samples after 24 h of reperfusion. Peptides were analyzed on the Q-Exactive (TM). In renal cortex proteome, we observed an increase in the synthesis of proteins in the ischemic kidney compared to the contralateral, highlighted by transcription factors and epithelial adherens junction proteins. Intersecting the set of proteins up- or down-regulated in the ischemic tissue with both serum and urine proteomes, we identified 6 proteins in the serum that may provide a set of targets for kidney injury. Additionally, we identified 49, being 4 predominantly renal, proteins in urine. As prove of concept, we validated one of the identified biomarkers, dipeptidyl peptidase IV, in a set of patients with diabetic nephropathy. In conclusion, we identified 55 systemic proteins, some of them predominantly renal, candidates for biomarkers of renal disease. Biological significance: The main bottleneck in studies aiming to identify novel biomarkers in acute kidney injury (AKI) has been the identification of markers that are predominantly renal. In fact, putative biomarkers for this condition have also been identified in a number of other clinical scenarios, such as cardiovascular diseases, chronic kidney failure or in patients being treated in intensive care units from a number of conditions. Here we propose a comprehensive, sequential screening procedure able to identify and validate potential biomarkers for kidney disease, using kidney ischemia/reperfusion as a paradigm for a kidney pathological event.
- Serum metabolomics profile of type 2 diabetes mellitus in a Brazilian rural population(2016) PADILHA, Kallyandra; VENTURINI, Gabriela; PIRES, Thiago de Farias; HORIMOTO, Andrea R. V. R.; MALAGRINO, Pamella Araujo; GOIS, Tamiris Carneiro; KIERS, Bianca; OLIVEIRA, Camila Maciel; ALVIM, Rafael de Oliveira; BLATT, Celso; KRIEGER, Jose Eduardo; PEREIRA, Alexandre CostaIntroduction The development of common forms of diabetes comes from the interaction between environmental and genetic factors, and the consequences of poor glycemic control in these patients could result in several complications. Metabolomic studies for type 2 diabetes mellitus in serum/plasma have reported changes in numerous metabolites, which might be considered possible targets for future mechanistic research. However, the specific role of a particular metabolite as cause or consequence of diabetes derangements is difficult to establish. Objectives As type 2 diabetes is a disease that changes the metabolic profile in several levels, this work aimed to compare the metabolomic profiles of type 2 diabetes mellitus and non-diabetic participants. In addition, we exploited our family-based study design to bring a better understanding of the causal relationship of identified metabolites and diabetes. Methods In the current study, population based metabolomics was applied in 939 subjects from the Baependi Heart Study. Participants were separated into two groups: diabetic (77 individuals) and non-diabetic (862 individuals), and the metabolic profile was performed by GC/MS technique. Results We have identified differentially concentrated metabolites in serum of diabetic and non-diabetic individuals. We identified 72 metabolites up-regulated in type 2 diabetes mellitus compared to non-diabetics. It was possible to recapitulate the main pathways that the literature shows as changed in diabetes. Also, based on metabolomic profile, we separated pre-diabetic individuals (with glucose concentration between 100-125 mg/dL) from non-diabetics and diabetics. Finally, using heritability analysis, we were able to suggest metabolites in which altered levels may precede diabetic development. Conclusion Our data can be used to derive a better understanding of the causal relationship of the observed associations and help to prioritize diabetes-associated metabolites for further work.
- Metabolomic characterization of renal ischemia and reperfusion in a swine model(2016) 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; GIRARDI, Adriana Castello Costa; CARNEVALE, Francisco Cesar; CANEVAROLO, Rafael; MALHEIROS, Denise Maria Avancini Costa; ZERI, Ana Carolina de Mattos; KRIEGER, Jose Eduardo; PEREIRA, Alexandre CostaAcute kidney injury (AKI) is a serious complication in hospitalized and transplanted patients, and is mainly caused by ischemia/reperfusion (I/R). However, the current diagnosis of AKI based on acute alterations in serum creatinine or urine output is late and unspecific. To identify new systemic biomarkers for AKI, we performed serum and urine metabolomic profile analyses during percutaneous unilateral renal I/R in a well-controlled swine model. For this, serial serum and urine samples obtained during the pre-ischemia, ischemia and reperfusion periods were analyzed by H-1 nuclear magnetic resonance at 600 MHz. Through the metabolic profiles over I/R, we identified eight serum metabolites that increased with ischemia and recovered to basal values after reperfusion, delineating the ischemic period. In addition, we identified 13 urinary metabolites that changed during the early reperfusion reflecting the ischemic kidney, being able to differentiate between pre-ischemia and post I/R periods. All selected metabolites are described in terms of disease pathophysiology (change of energetic pathway and oxidative stress), which suggest that these serum and urinary metabolites are candidate AKI biomarkers. Interestingly, the selected metabolites allowed us to identify, well described NF kappa B, leptin, INF-gamma and insulin pathways, and a new pathway (Huntingtin) that had not been previously implicated in renal I/R. Huntingtin showed different fragment patterns in ischemic versus non-ischemic kidneys. Therefore, the metabolomic profile found in renal I/R led to the identification of candidate disease biomarkers and a new pathway associated with renal injury.
- Integrated proteomics and metabolomics analysis reveals differential lipid metabolism in human umbilical vein endothelial cells under high and low shear stress(2019) VENTURINI, Gabriela; MALAGRINO, Pamella Araujo; PADILHA, Kallyandra; TANAKA, Leonardo Yuji; LAURINDO, Francisco Rafael; DARIOLLI, Rafael; CARVALHO, Valdemir Melechco; CARDOZO, Karina Helena Morais; KRIEGER, Jose Eduardo; PEREIRA, Alexandre da CostaAtherosclerotic plaque development is closely associated with the hemodynamic forces applied to endothelial cells (ECs). Among these, shear stress (SS) plays a key role in disease development since changes in flow intensity and direction could stimulate an atheroprone or atheroprotective phenotype. ECs under low or oscillatory SS (LSS) show upregulation of inflammatory, adhesion, and cellular permeability molecules. On the contrary, cells under high or laminar SS (HSS) increase their expression of protective and anti-inflammatory factors. The mechanism behind SS regulation of an atheroprotective phenotype is not completely elucidated. Here we used proteomics and metabolomics to better understand the changes in endothelial cells (human umbilical vein endothelial cells) under in vitro LSS and HSS that promote an atheroprone or atheroprotective profile and how these modifications can be connected to atherosclerosis development. Our data showed that lipid metabolism, in special cholesterol metabolism, was downregulated in cells under LSS. The low-density lipoprotein receptor (LDLR) showed significant alterations both at the quantitative expression level as well as regarding posttranslational modifications. Under LSS, LDLR was seen at lower concentrations and with a different glycosylation profile. Finally, modulating LDLR with atorvastatin led to the recapitulation of a HSS metabolic phenotype in EC under LSS. Altogether. our data suggest that there is significant modulation of lipid metabolism in endothelial cells under different SS intensities and that this could contribute to the atheroprone phenotype of LSS. Statin treatment was able to partially recover the protective profile of these cells.
- 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).