Kátia Da Silveira - Academia.edu (original) (raw)

Papers by Kátia Da Silveira

Research paper thumbnail of Mas and Inflammation

The Protective Arm of the Renin Angiotensin System (RAS), 2015

The renin–angiotensin system (RAS) is thought to contribute significantly to inflammation and fib... more The renin–angiotensin system (RAS) is thought to contribute significantly to inflammation and fibrosis. The classical axis of the RAS, formed by angiotensin-converting enzyme (ACE), angiotensin (Ang) II, and Ang receptor type 1, activates several cell functions and molecular signaling pathways related to tissue injury, inflammation, and fibrosis. In sharp contrast, the RAS axis composed by ­angiotensin-converting enzyme 2 (ACE2), Ang-(1-7), and receptor Mas exerts in general opposite effects with reported anti-­inflammatory and antifibrogenic responses. In this chapter, we briefly report recent findings on the anti-inflammatory and antifibrogenic role of ACE2/Ang-(1-7)/Mas axis in the context of experimental human diseases.

Research paper thumbnail of Urinary levels of TGF β-1 and of cytokines in patients with prenatally detected nephrouropathies

Pediatric Nephrology, 2011

This study aimed to identify noninvasive biomarkers of clinically significant nephrouropathies in... more This study aimed to identify noninvasive biomarkers of clinically significant nephrouropathies in patients with antenatal renal and/or urinary tract alterations. Spot-urine levels of interleukin-6 (IL-6), transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) were measured in 100 patients with antenatal detected nephrouropathies. Patients were divided in idiopathic hydronephrosis (n = 47), urinary tract malformations (n = 35), and dysplastic kidneys (n = 18). Urinary concentrations of TGF-β1, IL-6, and TNF-α were compared between groups according to clinical and image findings. Receiver-operating characteristic (ROC) curves were analyzed for the overall diagnostic accuracy of TGF-β1, IL-6, and TNF-α levels in discriminating infants with nephrouropathies. No significant differences in urinary TGF- β1, IL-6, and TNF-α levels were found in the comparison between the groups. TGF-β1 levels tended to be higher in patients with renal hypodysplasia compared to idiopathic hydronephrosis (p = 0.07). Twenty-nine patients had reduced DMSA uptake. In these cases, absolute urinary concentration of TGF-β1 and levels standardized for creatinine were significantly higher than in patients with normal DMSA uptake, while IL6 and TNF-α did not differ between groups. Urinary cytokine measurements were not useful as a screening test for clinically significant nephrouropathies. Conversely, increased concentrations of TGF-β1 pointed out to renal damage as indicated by reduced DMSA uptake.

Research paper thumbnail of Genetic deletion of the angiotensin-(1–7) receptor Mas leads to glomerular hyperfiltration and microalbuminuria

Kidney International, 2009

Angiotensin-(1-7), an active fragment of both angiotensins I and II, generally opposes the vascul... more Angiotensin-(1-7), an active fragment of both angiotensins I and II, generally opposes the vascular and proliferative actions of angiotensin II. Here we evaluated effects of the angiotensin-(1-7) receptor Mas on renal physiology and morphology using Mas-knockout mice. Compared to the wild-type animals, Mas knockout mice had significant reductions in urine volume and fractional sodium excretion without any significant change in free-water clearance. A significantly higher inulin clearance and microalbuminuria concomitant with a reduced renal blood flow suggest that glomerular hyperfiltration occurs in the knockout mice. Histological analysis found reduced glomerular tuft diameter and increased expression of collagen IV and fibronectin in the both the mesangium and interstitium, along with increased collagen III in the interstitium. These fibrogenic changes and the renal dysfunction of the knockout mice were associated with an upregulation of angiotensin II AT1 receptor and transforming growth factor-b mRNA. Our study suggests that Mas acts as a critical regulator of renal fibrogenesis by controlling effects transduced through angiotensin II AT1 receptors in the kidney.

Research paper thumbnail of ACE2, angiotensin-(1-7) and Mas receptor axis in inflammation and fibrosis

British Journal of Pharmacology, 2013

Recent advances have improved our understanding of the renin-angiotensin system (RAS). These have... more Recent advances have improved our understanding of the renin-angiotensin system (RAS). These have included the recognition that angiotensin (Ang)-(1-7) is a biologically active product of the RAS cascade. The identification of the ACE homologue ACE2, which forms Ang-(1-7) from Ang II, and the GPCR Mas as an Ang-(1-7) receptor have provided the necessary biochemical and molecular background and tools to study the biological significance of Ang-(1-7). Most available evidence supports a counter-regulatory role for Ang-(1-7) by opposing many actions of Ang II on AT₁ receptors, especially vasoconstriction and proliferation. Many studies have now shown that Ang-(1-7) by acting via Mas receptor exerts inhibitory effects on inflammation and on vascular and cellular growth mechanisms. Ang-(1-7) has also been shown to reduce key signalling pathways and molecules thought to be relevant for fibrogenesis. Here, we review recent findings related to the function of the ACE2/Ang-(1-7)/Mas axis and focus on the role of this axis in modifying processes associated with acute and chronic inflammation, including leukocyte influx, fibrogenesis and proliferation of certain cell types. More attention will be given to the involvement of the ACE2/Ang-(1-7)/Mas axis in the context of renal disease because of the known relevance of the RAS for the function of this organ and for the regulation of kidney inflammation and fibrosis. Taken together, this knowledge may help in paving the way for the development of novel treatments for chronic inflammatory and renal diseases.

Research paper thumbnail of ACE2-angiotensin-(1-7)-Mas axis in renal ischaemia/reperfusion injury in rats

A B S T R A C T AngII (angiotensin II), ACE (angiotensin I-converting enzyme) and the AT 1 recept... more A B S T R A C T AngII (angiotensin II), ACE (angiotensin I-converting enzyme) and the AT 1 receptor (AngII type 1 receptor) are associated with the inflammatory process and microvascular dysfunction of AKI (acute kidney injury) induced by renal I/R (ischaemia/reperfusion). However, Ang-(1-7) [angiotensin-(1-7)], ACE2 (angiotensin I-converting enzyme 2) and the Mas receptor also play a role in renal disease models. Therefore, in the present study, we have examined the renal profile of Ang-(1-7), ACE2 and the Mas receptor in renal I/R and compared them with that of AngII, ACE and the AT 1 receptor. Male Wistar rats were submitted to left nephrectomy and ischaemia (45 min) followed by reperfusion (2 or 4 h) in the right kidney. At 4 h of reperfusion, renal AngII was increased (P < 0.01) and renal Ang-(1-7) was decreased substantially (P < 0.05), although plasma levels of both angiotensins were unchanged. In addition, renal I/R decreased the renal mRNA expression of renin (P < ...

Research paper thumbnail of Posterior urethral valve in fetuses: evidence for the role of inflammatory molecules

BackgroundThe aim of this cross-sectional study was to investigate inflammatory biomarkers in uri... more BackgroundThe aim of this cross-sectional study was to investigate inflammatory biomarkers in urine samples of 24 fetuses with posterior urethral valve (PUV) collected at 22 ± 4 weeks of gestation and to compare the findings with measurements in urine samples of 22 male healthy preterm neonates at 23 ± 4 weeks (control group).MethodsInflammatory biomarkers in urine were measured using a cytometric bead array [interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN)-γ, soluable tumor necrosis factor receptor (TNFR) 1, sTNFR2, monocyte chemoattractant protein-1/chemokine ligand 2 (MCP-1/CCL2), eotaxin/CCL11 and interferon gamma-induced protein/10/C-X-C motif chemokine 10 (IP-10/CXCL10)] and ELISA assays [TNF, IL-8/CXCL8 and transforming growth factor-beta (TGF-β)]. The Mann–Whitney test was used to compare medians. Markers of glomerular (creatinine) and tubular [beta 2 (β2)-microglobulin, uromodulin, osmolality] functions were correlated with inflammatory biomarkers (Spearman test).Res...

Research paper thumbnail of Bj-PRO-5a and Bj-PRO 10c Found at C-Type Natriuretic Peptide Precursor of Bothrops jararaca Change Renal Function of Hypertensive Rats

International Journal of Peptide Research and Therapeutics, 2017

Proline-rich oligopeptides from Bothrops jararaca (Bj-PROs) produce potent and long-lasting antih... more Proline-rich oligopeptides from Bothrops jararaca (Bj-PROs) produce potent and long-lasting antihypertensive effect through mechanisms that go beyond ACE inhibition. In this study we evaluated the renal function parameters of spontaneously hypertensive rats (SHR) injected with Bj-PRO-5a and -10c (0.47, 71 or 710 nmol/kg) found in the CNP-precursor of the snake. At 71 and 710 nmol/kg, Bj-PROs increased urinary flow rate (18.1–43.5%). At 71 nmol/kg, Bj-PRO 5a and 10c elevated sodium excretion (68.1 and 40.9%, respectively) and Bj-PRO-5a also increased urinary sodium/creatinine ratio (56.5%). At 0.47 nmol/kg, Bj-PROs did not change renal function. All doses of Bj-PROs reduced blood pressure (Δ = −13 to −24mmHg). We conclude that Bj-PROs reduce blood pressure and improve renal function of SHRs through diuretic and natriuretic mechanisms.

Research paper thumbnail of Characterization of an experimental model of progressive renal disease in rats

Acta cirurgica brasileira, 2016

To characterize an experimental model of progressive renal disease induced by different degrees o... more To characterize an experimental model of progressive renal disease induced by different degrees of nephrectomy in rats. Eighty male Wistar rats were divided into four experimental groups (n=20/group): sham surgery (control group), progressive degrees of nephrectomy leading to mild uremia (group 1), moderate uremia (group 2) and severe uremia (group 3). Ten animals of each group were followed for two or four weeks. At the end, blood and 24-hour urine samples were collected to determine renal function parameters. Urine output and water and food intake were daily monitored. In rats of group 1, serum levels of creatinine and urea and microalbuminuria were increased, while reduced creatinine clearance (p<0.05, compared with control group), without changing blood pressure. Animals of group 2 had more accentuated alterations: increases in urinary output, blood pressure, serum concentrations of urea, creatinine, sodium, potassium, and in microalbuminuria, and reduction of creatinine clea...

Research paper thumbnail of Urinary cytokine profiles according to the site of blockade of the renin-angiotensin system in nephrectomized rats

Urinary cytokine profiles according to the site of blockade of the renin-angiotensin system in ne... more Urinary cytokine profiles according to the site of blockade of the renin-angiotensin system in nephrectomized rats Perfil de citocinas urinárias de acordo com o local de bloqueio do Sistema Renina Angiotensina em ratos nefrectomizados

Research paper thumbnail of ACE2, angiotensin-(1-7) and Mas receptor axis in inflammation and fibrosis.

Research paper thumbnail of Mas and Inflammation

The Protective Arm of the Renin Angiotensin System (RAS), 2015

Research paper thumbnail of Urinary levels of TGF β-1 and of cytokines in patients with prenatally detected nephrouropathies

Pediatric Nephrology, 2011

This study aimed to identify noninvasive biomarkers of clinically significant nephrouropathies in... more This study aimed to identify noninvasive biomarkers of clinically significant nephrouropathies in patients with antenatal renal and/or urinary tract alterations. Spot-urine levels of interleukin-6 (IL-6), transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) were measured in 100 patients with antenatal detected nephrouropathies. Patients were divided in idiopathic hydronephrosis (n=47), urinary tract malformations (n=35), and dysplastic kidneys (n=18). Urinary concentrations of TGF-β1, IL-6, and TNF-α were compared between groups according to clinical and image findings. Receiver-operating characteristic (ROC) curves were analyzed for the overall diagnostic accuracy of TGF-β1, IL-6, and TNF-α levels in discriminating infants with nephrouropathies. No significant differences in urinary TGF-β1, IL-6, and TNF-α levels were found in the comparison between the groups. TGF-β1 levels tended to be higher in patients with renal hypodysplasia compared to idiopathic hydronephrosis (p=0.07). Twenty-nine patients had reduced DMSA uptake. In these cases, absolute urinary concentration of TGF-β1 and levels standardized for creatinine were significantly higher than in patients with normal DMSA uptake, while IL6 and TNF-α did not differ between groups. Urinary cytokine measurements were not useful as a screening test for clinically significant nephrouropathies. Conversely, increased concentrations of TGF-β1 pointed out to renal damage as indicated by reduced DMSA uptake.

Research paper thumbnail of Anti-Inflammatory Effects of the Activation of the Angiotensin-(1-7) Receptor, Mas, in Experimental Models of Arthritis

The Journal of Immunology, 2010

Research paper thumbnail of ACE2–angiotensin-(1–7)–Mas axis in renal ischaemia/reperfusion injury in rats

Clinical Science, 2010

AngII (angiotensin II), ACE (angiotensin I-converting enzyme) and AT 1 receptor are associated wi... more AngII (angiotensin II), ACE (angiotensin I-converting enzyme) and AT 1 receptor are associated with the inflammatory process and microvascular dysfunction of AKI (acute kidney injury) induced by renal I (ischemia) and R (reperfusion). However, Ang(1-7) (angiotensin-(1-7)), ACE2 and Mas receptor also play a role in renal disease models. Therefore, in this study we have examined the renal profile of Ang(1-7), ACE2 and Mas receptor in renal I/R and compared to AngII, ACE and AT 1 receptor. Male Wistar rats were submitted to left nephrectomy and I (45 min) followed by R (2 or 4 h) in the right kidney. At 4 h of R, renal AngII was increased (p < 0.01) and renal Ang(1-7) intensively decreased (p < 0.05), although plasma levels of both angiotensins were unchanged. In addition, renal I/R decreased renal mRNA expression of renin (p < 0.05), AT 1 receptors (p < 0.001) and ACE2 (p < 0.05). At 2 and 4 h of R, renal ACE activity was reduced (p < 0.05). On the other hand, renal expression of Mas receptor was greatly increased at 4 h of R (p < 0.01), which was confirmed by immunohistochemical and Western blot analysis. Increased renal expression of Mas receptor associated with changes in RAS (renin-angiotensin-system)related peptidases support an important role for ACE2-Ang(1-7)-Mas axis in AKI.

Research paper thumbnail of Contributors

The Protective Arm of the Renin Angiotensin System (RAS), 2015

Research paper thumbnail of Mas and Inflammation

The Protective Arm of the Renin Angiotensin System (RAS), 2015

The renin–angiotensin system (RAS) is thought to contribute significantly to inflammation and fib... more The renin–angiotensin system (RAS) is thought to contribute significantly to inflammation and fibrosis. The classical axis of the RAS, formed by angiotensin-converting enzyme (ACE), angiotensin (Ang) II, and Ang receptor type 1, activates several cell functions and molecular signaling pathways related to tissue injury, inflammation, and fibrosis. In sharp contrast, the RAS axis composed by ­angiotensin-converting enzyme 2 (ACE2), Ang-(1-7), and receptor Mas exerts in general opposite effects with reported anti-­inflammatory and antifibrogenic responses. In this chapter, we briefly report recent findings on the anti-inflammatory and antifibrogenic role of ACE2/Ang-(1-7)/Mas axis in the context of experimental human diseases.

Research paper thumbnail of Urinary levels of TGF β-1 and of cytokines in patients with prenatally detected nephrouropathies

Pediatric Nephrology, 2011

This study aimed to identify noninvasive biomarkers of clinically significant nephrouropathies in... more This study aimed to identify noninvasive biomarkers of clinically significant nephrouropathies in patients with antenatal renal and/or urinary tract alterations. Spot-urine levels of interleukin-6 (IL-6), transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) were measured in 100 patients with antenatal detected nephrouropathies. Patients were divided in idiopathic hydronephrosis (n = 47), urinary tract malformations (n = 35), and dysplastic kidneys (n = 18). Urinary concentrations of TGF-β1, IL-6, and TNF-α were compared between groups according to clinical and image findings. Receiver-operating characteristic (ROC) curves were analyzed for the overall diagnostic accuracy of TGF-β1, IL-6, and TNF-α levels in discriminating infants with nephrouropathies. No significant differences in urinary TGF- β1, IL-6, and TNF-α levels were found in the comparison between the groups. TGF-β1 levels tended to be higher in patients with renal hypodysplasia compared to idiopathic hydronephrosis (p = 0.07). Twenty-nine patients had reduced DMSA uptake. In these cases, absolute urinary concentration of TGF-β1 and levels standardized for creatinine were significantly higher than in patients with normal DMSA uptake, while IL6 and TNF-α did not differ between groups. Urinary cytokine measurements were not useful as a screening test for clinically significant nephrouropathies. Conversely, increased concentrations of TGF-β1 pointed out to renal damage as indicated by reduced DMSA uptake.

Research paper thumbnail of Genetic deletion of the angiotensin-(1–7) receptor Mas leads to glomerular hyperfiltration and microalbuminuria

Kidney International, 2009

Angiotensin-(1-7), an active fragment of both angiotensins I and II, generally opposes the vascul... more Angiotensin-(1-7), an active fragment of both angiotensins I and II, generally opposes the vascular and proliferative actions of angiotensin II. Here we evaluated effects of the angiotensin-(1-7) receptor Mas on renal physiology and morphology using Mas-knockout mice. Compared to the wild-type animals, Mas knockout mice had significant reductions in urine volume and fractional sodium excretion without any significant change in free-water clearance. A significantly higher inulin clearance and microalbuminuria concomitant with a reduced renal blood flow suggest that glomerular hyperfiltration occurs in the knockout mice. Histological analysis found reduced glomerular tuft diameter and increased expression of collagen IV and fibronectin in the both the mesangium and interstitium, along with increased collagen III in the interstitium. These fibrogenic changes and the renal dysfunction of the knockout mice were associated with an upregulation of angiotensin II AT1 receptor and transforming growth factor-b mRNA. Our study suggests that Mas acts as a critical regulator of renal fibrogenesis by controlling effects transduced through angiotensin II AT1 receptors in the kidney.

Research paper thumbnail of ACE2, angiotensin-(1-7) and Mas receptor axis in inflammation and fibrosis

British Journal of Pharmacology, 2013

Recent advances have improved our understanding of the renin-angiotensin system (RAS). These have... more Recent advances have improved our understanding of the renin-angiotensin system (RAS). These have included the recognition that angiotensin (Ang)-(1-7) is a biologically active product of the RAS cascade. The identification of the ACE homologue ACE2, which forms Ang-(1-7) from Ang II, and the GPCR Mas as an Ang-(1-7) receptor have provided the necessary biochemical and molecular background and tools to study the biological significance of Ang-(1-7). Most available evidence supports a counter-regulatory role for Ang-(1-7) by opposing many actions of Ang II on AT₁ receptors, especially vasoconstriction and proliferation. Many studies have now shown that Ang-(1-7) by acting via Mas receptor exerts inhibitory effects on inflammation and on vascular and cellular growth mechanisms. Ang-(1-7) has also been shown to reduce key signalling pathways and molecules thought to be relevant for fibrogenesis. Here, we review recent findings related to the function of the ACE2/Ang-(1-7)/Mas axis and focus on the role of this axis in modifying processes associated with acute and chronic inflammation, including leukocyte influx, fibrogenesis and proliferation of certain cell types. More attention will be given to the involvement of the ACE2/Ang-(1-7)/Mas axis in the context of renal disease because of the known relevance of the RAS for the function of this organ and for the regulation of kidney inflammation and fibrosis. Taken together, this knowledge may help in paving the way for the development of novel treatments for chronic inflammatory and renal diseases.

Research paper thumbnail of ACE2-angiotensin-(1-7)-Mas axis in renal ischaemia/reperfusion injury in rats

A B S T R A C T AngII (angiotensin II), ACE (angiotensin I-converting enzyme) and the AT 1 recept... more A B S T R A C T AngII (angiotensin II), ACE (angiotensin I-converting enzyme) and the AT 1 receptor (AngII type 1 receptor) are associated with the inflammatory process and microvascular dysfunction of AKI (acute kidney injury) induced by renal I/R (ischaemia/reperfusion). However, Ang-(1-7) [angiotensin-(1-7)], ACE2 (angiotensin I-converting enzyme 2) and the Mas receptor also play a role in renal disease models. Therefore, in the present study, we have examined the renal profile of Ang-(1-7), ACE2 and the Mas receptor in renal I/R and compared them with that of AngII, ACE and the AT 1 receptor. Male Wistar rats were submitted to left nephrectomy and ischaemia (45 min) followed by reperfusion (2 or 4 h) in the right kidney. At 4 h of reperfusion, renal AngII was increased (P < 0.01) and renal Ang-(1-7) was decreased substantially (P < 0.05), although plasma levels of both angiotensins were unchanged. In addition, renal I/R decreased the renal mRNA expression of renin (P < ...

Research paper thumbnail of Posterior urethral valve in fetuses: evidence for the role of inflammatory molecules

BackgroundThe aim of this cross-sectional study was to investigate inflammatory biomarkers in uri... more BackgroundThe aim of this cross-sectional study was to investigate inflammatory biomarkers in urine samples of 24 fetuses with posterior urethral valve (PUV) collected at 22 ± 4 weeks of gestation and to compare the findings with measurements in urine samples of 22 male healthy preterm neonates at 23 ± 4 weeks (control group).MethodsInflammatory biomarkers in urine were measured using a cytometric bead array [interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN)-γ, soluable tumor necrosis factor receptor (TNFR) 1, sTNFR2, monocyte chemoattractant protein-1/chemokine ligand 2 (MCP-1/CCL2), eotaxin/CCL11 and interferon gamma-induced protein/10/C-X-C motif chemokine 10 (IP-10/CXCL10)] and ELISA assays [TNF, IL-8/CXCL8 and transforming growth factor-beta (TGF-β)]. The Mann–Whitney test was used to compare medians. Markers of glomerular (creatinine) and tubular [beta 2 (β2)-microglobulin, uromodulin, osmolality] functions were correlated with inflammatory biomarkers (Spearman test).Res...

Research paper thumbnail of Bj-PRO-5a and Bj-PRO 10c Found at C-Type Natriuretic Peptide Precursor of Bothrops jararaca Change Renal Function of Hypertensive Rats

International Journal of Peptide Research and Therapeutics, 2017

Proline-rich oligopeptides from Bothrops jararaca (Bj-PROs) produce potent and long-lasting antih... more Proline-rich oligopeptides from Bothrops jararaca (Bj-PROs) produce potent and long-lasting antihypertensive effect through mechanisms that go beyond ACE inhibition. In this study we evaluated the renal function parameters of spontaneously hypertensive rats (SHR) injected with Bj-PRO-5a and -10c (0.47, 71 or 710 nmol/kg) found in the CNP-precursor of the snake. At 71 and 710 nmol/kg, Bj-PROs increased urinary flow rate (18.1–43.5%). At 71 nmol/kg, Bj-PRO 5a and 10c elevated sodium excretion (68.1 and 40.9%, respectively) and Bj-PRO-5a also increased urinary sodium/creatinine ratio (56.5%). At 0.47 nmol/kg, Bj-PROs did not change renal function. All doses of Bj-PROs reduced blood pressure (Δ = −13 to −24mmHg). We conclude that Bj-PROs reduce blood pressure and improve renal function of SHRs through diuretic and natriuretic mechanisms.

Research paper thumbnail of Characterization of an experimental model of progressive renal disease in rats

Acta cirurgica brasileira, 2016

To characterize an experimental model of progressive renal disease induced by different degrees o... more To characterize an experimental model of progressive renal disease induced by different degrees of nephrectomy in rats. Eighty male Wistar rats were divided into four experimental groups (n=20/group): sham surgery (control group), progressive degrees of nephrectomy leading to mild uremia (group 1), moderate uremia (group 2) and severe uremia (group 3). Ten animals of each group were followed for two or four weeks. At the end, blood and 24-hour urine samples were collected to determine renal function parameters. Urine output and water and food intake were daily monitored. In rats of group 1, serum levels of creatinine and urea and microalbuminuria were increased, while reduced creatinine clearance (p<0.05, compared with control group), without changing blood pressure. Animals of group 2 had more accentuated alterations: increases in urinary output, blood pressure, serum concentrations of urea, creatinine, sodium, potassium, and in microalbuminuria, and reduction of creatinine clea...

Research paper thumbnail of Urinary cytokine profiles according to the site of blockade of the renin-angiotensin system in nephrectomized rats

Urinary cytokine profiles according to the site of blockade of the renin-angiotensin system in ne... more Urinary cytokine profiles according to the site of blockade of the renin-angiotensin system in nephrectomized rats Perfil de citocinas urinárias de acordo com o local de bloqueio do Sistema Renina Angiotensina em ratos nefrectomizados

Research paper thumbnail of ACE2, angiotensin-(1-7) and Mas receptor axis in inflammation and fibrosis.

Research paper thumbnail of Mas and Inflammation

The Protective Arm of the Renin Angiotensin System (RAS), 2015

Research paper thumbnail of Urinary levels of TGF β-1 and of cytokines in patients with prenatally detected nephrouropathies

Pediatric Nephrology, 2011

This study aimed to identify noninvasive biomarkers of clinically significant nephrouropathies in... more This study aimed to identify noninvasive biomarkers of clinically significant nephrouropathies in patients with antenatal renal and/or urinary tract alterations. Spot-urine levels of interleukin-6 (IL-6), transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) were measured in 100 patients with antenatal detected nephrouropathies. Patients were divided in idiopathic hydronephrosis (n=47), urinary tract malformations (n=35), and dysplastic kidneys (n=18). Urinary concentrations of TGF-β1, IL-6, and TNF-α were compared between groups according to clinical and image findings. Receiver-operating characteristic (ROC) curves were analyzed for the overall diagnostic accuracy of TGF-β1, IL-6, and TNF-α levels in discriminating infants with nephrouropathies. No significant differences in urinary TGF-β1, IL-6, and TNF-α levels were found in the comparison between the groups. TGF-β1 levels tended to be higher in patients with renal hypodysplasia compared to idiopathic hydronephrosis (p=0.07). Twenty-nine patients had reduced DMSA uptake. In these cases, absolute urinary concentration of TGF-β1 and levels standardized for creatinine were significantly higher than in patients with normal DMSA uptake, while IL6 and TNF-α did not differ between groups. Urinary cytokine measurements were not useful as a screening test for clinically significant nephrouropathies. Conversely, increased concentrations of TGF-β1 pointed out to renal damage as indicated by reduced DMSA uptake.

Research paper thumbnail of Anti-Inflammatory Effects of the Activation of the Angiotensin-(1-7) Receptor, Mas, in Experimental Models of Arthritis

The Journal of Immunology, 2010

Research paper thumbnail of ACE2–angiotensin-(1–7)–Mas axis in renal ischaemia/reperfusion injury in rats

Clinical Science, 2010

AngII (angiotensin II), ACE (angiotensin I-converting enzyme) and AT 1 receptor are associated wi... more AngII (angiotensin II), ACE (angiotensin I-converting enzyme) and AT 1 receptor are associated with the inflammatory process and microvascular dysfunction of AKI (acute kidney injury) induced by renal I (ischemia) and R (reperfusion). However, Ang(1-7) (angiotensin-(1-7)), ACE2 and Mas receptor also play a role in renal disease models. Therefore, in this study we have examined the renal profile of Ang(1-7), ACE2 and Mas receptor in renal I/R and compared to AngII, ACE and AT 1 receptor. Male Wistar rats were submitted to left nephrectomy and I (45 min) followed by R (2 or 4 h) in the right kidney. At 4 h of R, renal AngII was increased (p < 0.01) and renal Ang(1-7) intensively decreased (p < 0.05), although plasma levels of both angiotensins were unchanged. In addition, renal I/R decreased renal mRNA expression of renin (p < 0.05), AT 1 receptors (p < 0.001) and ACE2 (p < 0.05). At 2 and 4 h of R, renal ACE activity was reduced (p < 0.05). On the other hand, renal expression of Mas receptor was greatly increased at 4 h of R (p < 0.01), which was confirmed by immunohistochemical and Western blot analysis. Increased renal expression of Mas receptor associated with changes in RAS (renin-angiotensin-system)related peptidases support an important role for ACE2-Ang(1-7)-Mas axis in AKI.

Research paper thumbnail of Contributors

The Protective Arm of the Renin Angiotensin System (RAS), 2015