ADRIANA CASTELLO COSTA GIRARDI
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Cardio-Pneumologia, Faculdade de Medicina - Docente
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/13 - Laboratório de Genética e Cardiologia Molecular, Hospital das Clínicas, Faculdade de Medicina
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/13 - Laboratório de Genética e Cardiologia Molecular, Hospital das Clínicas, Faculdade de Medicina
86 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 86
- RENAL DENERVATION DECREASES NA plus /CL- CO-TRANSPORTER (NCC) IN GOLDBLATT MODEL OF HYPERTENSION(2016) SHIMOURA, C. G.; LINCEVICIUS, G. S.; OLIVEIRA-SALES, E. B.; PONTES, R. B.; GIRARD, A. C.; BERGAMASCHI, C. T.; CAMPOS, R. R.
- Circulating Dipeptidyl Peptidase IV Activity Correlates With Cardiac Dysfunction in Human and Experimental Heart Failure(2013) SANTOS, Leonardo dos; SALLES, Thiago A.; ARRUDA-JUNIOR, Daniel F.; CAMPOS, Luciene C. G.; PEREIRA, Alexandre C.; BARRETO, Ana Luiza T.; ANTONIO, Ednei L.; MANSUR, Alfredo J.; TUCCI, Paulo J. F.; KRIEGER, Jose E.; GIRARDI, Adriana C. C.Background The present study addresses the hypothesis that the activity of dipeptidyl peptidase IV (DPPIV), an enzyme that inactivates peptides that possess cardioprotective actions, correlates with adverse outcomes in heart failure (HF). The therapeutic potential of DPPIV inhibition in preventing cardiac dysfunction is also investigated. Methods and Results Measurements of DPPIV activity in blood samples obtained from 190 patients with HF and 42 controls demonstrated that patients with HF exhibited an increase of approximate to 130% in circulating DPPIV activity compared with healthy subjects. Furthermore, an inverse correlation was observed between serum DPPIV activity and left ventricular (LV) ejection fraction in patients with HF. Similarly, radiofrequency LV ablation-induced HF rats displayed higher DPPIV activity in the plasma (approximate to 50%) and heart tissue (approximate to 3.5-fold) compared with sham-operated rats. Moreover, positive correlations were observed between the plasma DPPIV activity and LV end-diastolic pressure and lung congestion. Two days after surgery, 1 group of LV ablation-induced HF rats was treated with the DPPIV inhibitor sitagliptin (40 mg/kg BID) for 6 weeks, whereas the remaining rats were administered water. Hemodynamic measurements demonstrated that radiofrequency LV-ablated rats treated with sitagliptin exhibited a significant attenuation of HF-related cardiac dysfunction, including LV end-diastolic pressure, systolic performance, and chamber stiffness. Sitagliptin treatment also attenuated cardiac remodeling and cardiomyocyte apoptosis and minimized pulmonary congestion. Conclusions Collectively, the results presented herein associate circulating DPPIV activity with poorer cardiovascular outcomes in human and experimental HF. Moreover, the results demonstrate that long-term DPPIV inhibition mitigates the development and progression of HF in rats.
conferenceObject Angiotensin II decreases the levels of PKA-mediated NHE3 phosphorylation in renal proximal tubule(2012) ROSSETTO, Silmara Larissa; QUEIROZ-LEITE, Gabriella Duarte; CRAJOINAS, Renato Oliveira; OMAE, Samantha V.; MALNIC, Gerhard; GIRARDI, Adriana C.NHE3 transport function is inhibited by PKA. Binding of angiotensin II (ANG II) to AT1 receptor has been reported to activate Gi-protein signaling pathway, resulting in the inhibition of adenylyl cyclase, and consequently, in decreased PKA activation. We therefore tested the hypothesis that decrement of PKA-mediated NHE3 phosphorylation is one of the mechanisms by which ANG II acutely stimulates NHE3 activity in renal proximal tubule. To this end, OKP cells were treated with 100 μM Dopamine (DOP) for 30 min in the presence or absence of 10–10 M ANG II for 5, 15, and 30 min; or only with ANG II for 30 min. Extrusion of H+ from OKP cells was measured. DOP significantly inhibited NHE3 activity (0.2013 ± 0.009 vs. 0.3036 ± 0.0019 pH units/min in control). Simultaneous incubation of DOP with ANG II for 15 (0.2347 ± 0.044 pH units/min) and 30 min (0.3295 ± 0.032 pH units/min) completely blocked this inhibitory effect. As expected, ANG II stimulated NHE3 activity. DOP increased the levels of NHE3 phosphorylated at the PKA consensus phosphorylation sites [serines 552 and 605] by 64 ± 8% and 288 ± 37% respectively vs. control. ANG II treatment for 15 and 30 min prevented this increase. PKA activity was also measured in these groups of cells. We found that PKA activity was significantly increased in cells treated with DOP for 30 min and in cells treated with DOP plus ANG II for 5 min. Longer incubation times with ANG II (15 and 30 min) in the presence of DOP restored PKA activity near to control levels. Losartan blocked all the effects of ANG II here reported. Collectively, these data suggest that inhibition of PKA activity leading to lower levels of endogenous phosphorylation of NHE3 is one of the mechanisms by which ANG II stimulates NHE3 activity in the proximal tubule.conferenceObject Anti-inflammatory Effects of Dipeptidyl Peptidase IV (DPPIV) Inhibition in Heart Failure(2015) SALLES, Thiago; ZOGBI, Camila; LIMA, Thais; SORIANO, Francisco; GIRARDI, Adriana- The contributions of dipeptidyl peptidase IV to inflammation in heart failure(2016) SALLES, Thiago de Almeida; ZOGBI, Camila; LIMA, Thais Martins de; CARNEIRO, Camila de Godoi; GARCEZ, Alexandre Teles; BARBEIRO, Hermes Vieira; ANTONIO, Ednei Luiz; SANTOS, Leonardo dos; PEREIRA, Alexandre da Costa; TUCCI, Paulo Jose Ferreira; FARIA, Daniele de Paula; SORIANO, Francisco Garcia; GIRARDI, Adriana Castello CostaCirculating dipeptidyl peptidase IV (DPPIV) activity correlates with cardiac dysfunction in humans and experimental heart failure (HF) models. Similarly, inflammatory markers are associated with poorer outcomes in HF patients. However, the contributions of DPPIV to inflammation in HF remain elusive. Therefore, this study aimed to investigate whether the cardioprotective effects of DPPIV inhibition after myocardial injury are accompanied by reduced cardiac inflammation, whether circulating DPPIV activity correlates with the levels of systemic inflammatory markers in HF patients, and whether leukocytes and/or splenocytes may be one of the sources of circulating DPPIV in HF. Experimental HF was induced in male Wistar rats by left ventricular myocardial injury after radiofrequency catheter ablation. The rats were divided into three groups: sham, HF, and HF + DPPIV inhibitor (sitagliptin). Six weeks after surgery, cardiac function, perfusion and inflammatory status were evaluated. Sitagliptin treatment improved cardiac function and perfusion, reduced macrophage infiltration, and diminished the levels of inflammatory biomarkers including TNF-alpha, IL-1 beta, and CCL2. In HF patients, serum DPPIV activity correlated with CCL2, suggesting that leukocytes may be the source of circulating DPPIV in HF. Unexpectedly, DPPIV release was higher in splenocytes from HF rats and similar in HF circulating mononuclear cells compared with those from sham, suggesting an organ-specific modulation of DPPIV in HF. Collectively, our data provide new evidence that the cardioprotective effects of DPPIV inhibition in HF may be due to suppression of inflammatory cytokines. Moreover, they suggest that a vicious circle between DPPIV and inflammation may contribute to HF development and progression.
- Exercise Training Potentiates The Cardioprotective Effects of Stem Cells Post-infarction(2019) VIEIRA, Stella de Souza; ANTONIO, Ednei Luiz; MELO, Brunno Lemes de; PORTES, Leslie Andrews; MONTEMOR, Jairo; OLIVEIRA, Helenita Antonia; MARTINS, Flavia Leticia; ZOGBI, Camila; GIRARDI, Adriana Costa; SILVA JR., Jose Antonio; CARVALHO, Paulo de Tarso Camillo de; TUCCI, Paulo Jose Ferreira; SERRA, Andrey JorgeBackground Preconditioning of cell recipients may exert a significant role in attenuating the hostility of the infarction milieu, thereby enhancing the efficacy of cell therapy. This study was conducted to examine whether exercise training potentiates the cardioprotective effects of adipose-derived stern cell (ADSC) transplantation following myocardial infarction (MI) in rats. Methods Four groups of female Fisher-344 rats were studied: Sham; non-trained rats with MI (sMI); non-trained rats with Ml submitted to ADSCs transplantation (sADSC); trained rats with Ml submitted to ADSCs (tADSC). Rats were trained 9 weeks prior to MI and ADSCs transplantation. Echocardiography was applied to assess cardiac function. Myocardial performance was evaluated in vitro. Protein expression analyses were carried out by immunoblotting. Periodic acid-Schiff staining was used to analyse capillary density and apoptosis was evaluated with terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. Results Echocardiography performed 4 weeks after the infarction revealed attenuated scar size in the both sADSC and tADSC groups compared to the sMI group. However, fractional shortening was improved only in the tADSC group. In vitro myocardial performance was similar between the tADSC and Sham groups. The expression of phosphoSer473Akt1 and VEGF were found to be higher in the hearts of the tADSC group compared to both the sADSC and sMI groups. Histologic analysis demonstrated that tADSC rats had higher capillary density in the remote and border zones of the infarcted sites compared to the sMI rats. Conclusions Preconditioning with exercise induces a pro-angiogenic milieu that may potentiate the therapeutic effects of ADSCs on cardiac remodelling following MI.
- Mechanisms mediating the diuretic and natriuretic actions of the incretin hormone glucagon-like peptide-1(2011) CRAJOINAS, Renato O.; ORICCHIO, Felipe T.; PESSOA, Thaissa D.; PACHECO, Bruna P. M.; LESSA, Lucilia M. A.; MALNIC, Gerhard; GIRARDI, Adriana C. C.Crajoinas RO, Oricchio FT, Pessoa TD, Pacheco BP, Lessa LM, Malnic G, Girardi AC. Mechanisms mediating the diuretic and natriuretic actions of the incretin hormone glucagon-like peptide-1. Am J Physiol Renal Physiol 301: F355-F363, 2011. First published May 18, 2011; doi: 10.1152/ajprenal.00729.2010.-Glucagon-like peptide-1 (GLP-1) is a gut incretin hormone considered a promising therapeutic agent for type 2 diabetes because it stimulates beta cell proliferation and insulin secretion in a glucose-dependent manner. Cumulative evidence supports a role for GLP-1 in modulating renal function; however, the mechanisms by which GLP-1 induces diuresis and natriuresis have not been completely established. This study aimed to define the cellular and molecular mechanisms mediating the renal effects of GLP-1. GLP-1 (1 mu g.kg(-1).min(-1)) was intravenously administered in rats for the period of 60 min. GLP-1-infused rats displayed increased urine flow, fractional excretion of sodium, potassium, and bicarbonate compared with those rats that received vehicle (1% BSA/saline). GLP-1-induced diuresis and natriuresis were also accompanied by increases in renal plasma flow and glomerular filtration rate. Real-time RT-PCR in microdissected rat nephron segments revealed that GLP-1 receptor-mRNA expression was restricted to glomerulus and proximal convoluted tubule. In rat renal proximal tubule, GLP-1 significantly reduced Na+/H+ exchanger isoform 3 (NHE3)-mediated bicarbonate reabsorption via a protein kinase A (PKA)-dependent mechanism. Reduced proximal tubular bicarbonate flux rate was associated with a significant increase of NHE3 phosphorylation at the PKA consensus sites in microvillus membrane vesicles. Taken together, these data suggest that GLP-1 has diuretic and natriuretic effects that are mediated by changes in renal hemodynamics and by downregulation of NHE3 activity in the renal proximal tubule. Moreover, our findings support the view that GLP-1-based agents may have a potential therapeutic use not only as antidiabetic drugs but also in hypertension and other disorders of sodium retention.
conferenceObject A SINGLE LOW-LEVEL LASER APPLICATION REDUCES MYOCARDIAL INFARCTION SIZE, IMPROVES CARDIAC PERFORMANCE AND ATTENUATES APOPTOSIS IN REMOTE MYOCARDIUM(2016) GRANDINETTI, Vanessa; PIRES, Juliana; MANCHINI, Martha; ANTONIO, Ednei Luis; GIRARD, Adriana; SANTOS, Luis dos; CARVALHO, Paulo de Tarso Camillo de; TUCCI, Paulo; SILVA JUNIOR, Jose Antonio; SERRA, Andrey- Vitamin D deficiency is a potential risk factor for contrast-induced nephropathy(2015) LUCHI, Weverton M.; SHIMIZU, Maria Heloisa M.; CANALE, Daniele; GOIS, Pedro Henrique F.; BRAGANCA, Ana Carolina de; VOLPINI, Rildo A.; GIRARDI, Adriana C. C.; SEGURO, Antonio C.Vitamin D deficiency (VDD) is widespread in the general population. Iodinated (IC) or gadolinium-based contrast media (Gd) may decrease renal function in high-risk patients. This study tested the hypothesis that VDD is a predisposing factor for IC-or Gd-induced nephrotoxicity. To this end, male Wistar rats were fed standard (SD) or vitamin D-free diet for 30 days. IC (diatrizoate), Gd (gadoterate meglumine), or 0.9% saline was then administered intravenously and six groups were obtained as the following: SD plus 0.9% saline (Sham-SD), SD plus IC (SD + IC), SD plus Gd (SD + Gd), vitamin D-free diet for 30 days plus 0.9% saline (Sham-VDD30), vitamin D-free diet for 30 days plus IC (VDD30 + IC), and vitamin D-free diet for 30 days plus Gd (VDD30 + Gd). Renal hemodynamics, redox status, histological, and immunoblot analysis were evaluated 48 h after contrast media (CM) or vehicle infusion. VDD rats showed lower levels of total serum 25-hydroxyvitamin D [25(OH)D], similar plasma calcium and phosphorus concentration, and higher renal renin and angiotensinogen protein expression compared with rats fed SD. IC or Gd infusion did not affect inulin clearance-based estimated glomerular filtration rate (GFR) in rats fed SD but significantly decreased GFR in rats fed vitamin D-free diet. Both CM increased renal angiotensinogen, and the interaction between VDD and CM triggered lower renal endothelial nitric oxide synthase abundance and higher renal thiobarbituric acid reactive substances-to-glutathione ratio (an index of oxidative stress) on VDD30 + IC and VDD30 + Gd groups. Conversely, worsening of renal function was not accompanied by abnormalities on kidney structure. Additionally, rats on a VDD for 60 days displayed a greater fall in GFR after CM administration. Collectively, our findings suggest that VDD is a potential risk factor for IC-or Gd-induced nephrotoxicity most likely due to imbalance in intrarenal vasoactive substances and oxidative stress.
- Amelioration of Cardiac Function and Activation of Anti-Inflammatory Vasoactive Peptides Expression in the Rat Myocardium by Low Level Laser Therapy(2014) MANCHINI, Martha Trindade; SERRA, Andrey Jorge; FELICIANO, Regiane dos Santos; SANTANA, Eduardo Tadeu; ANTONIO, Ednei Luis; CARVALHO, Paulo de Tarso Camillo de; MONTEMOR, Jairo; CRAJOINAS, Renato Oliveira; GIRARDI, Adriana Castello Costa; TUCCI, Paulo Jose Ferreira; SILVA JR., Jose AntonioLow-level laser therapy (LLLT) has been used as an anti-inflammatory treatment in several disease conditions, even when inflammation is a secondary consequence, such as in myocardial infarction (MI). However, the mechanism by which LLLT is able to protect the remaining myocardium remains unclear. The present study tested the hypothesis that LLLT reduces inflammation after acute MI in female rats and ameliorates cardiac function. The potential participation of the Renin-Angiotensin System (RAS) and Kallikrein-Kinin System (KKS) vasoactive peptides was also evaluated. LLLT treatment effectively reduced MI size, attenuated the systolic dysfunction after MI, and decreased the myocardial mRNA expression of interleukin-1 beta and interleukin-6 in comparison to the non-irradiated rat tissue. In addition, LLLT treatment increased protein and mRNA levels of the Mas receptor, the mRNA expression of kinin B2 receptors and the circulating levels of plasma kallikrein compared to non-treated post-MI rats. On the other hand, the kinin B1 receptor mRNA expression decreased after LLLT. No significant changes were found in the expression of vascular endothelial growth factor (VEGF) in the myocardial remote area between laser-irradiated and non-irradiated post-MI rats. Capillaries density also remained similar between these two experimental groups. The mRNA expression of the inducible nitric oxide synthase (iNOS) was increased three days after MI, however, this effect was blunted by LLLT. Moreover, endothelial NOS mRNA content increased after LLLT. Plasma nitric oxide metabolites (NOx) concentration was increased three days after MI in non-treated rats and increased even further by LLLT treatment. Our data suggest that LLLT diminishes the acute inflammation in the myocardium, reduces infarct size and attenuates left ventricle dysfunction post-MI and increases vasoactive peptides expression and nitric oxide (NO) generation.