Reduced endothelial nitric oxide synthase activation contributes to cardiovascular injury during chronic kidney disease progression

Amador-Martínez, Isabel; Pérez‐Villalva, Rosalba; Uribe, Norma; Cortés‐González, Cesar; Bobadilla, Norma A.; Barrera‐Chimal, Jonatan

doi:10.1152/ajprenal.00020.2019

Cited by 31 publications

(28 citation statements)

References 46 publications

(63 reference statements)

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“…Studies have also shown the close relationship between the increase in angiotensin II and the increase in eNOS expression via a signaling cascade by angiotensin receptors [ 47 ]. Beside this increase, Amador-Martínez and his group [ 48 ] found that even with this eNOS increase, the heart tissue showed a decrease in eNOS enzyme activity. Based on these data, it is possible to assume that despite high expression on 8 d, eNOS is in a decoupled state, generating ROS such anion superoxide other than NO.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Oxidative Stress in Renal Ischemia/Reperfusion-Induced Cardiorenal Syndrome Type 3

Caio‐Silva

Dias

Junho

et al. 2020

BioMed Research International

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In kidney disease (KD), several factors released into the bloodstream can induce a series of changes in the heart, leading to a wide variety of clinical situations called cardiorenal syndrome (CRS). Reactive oxygen species (ROS) play an important role in the signaling and progression of systemic inflammatory conditions, as observed in KD. The aim of the present study was to characterize the redox balance in renal ischemia/reperfusion-induced cardiac remodeling. C57BL/6 male mice were subjected to occlusion of the left renal pedicle, unilateral, for 60 min, followed by reperfusion for 8 and 15 days, respectively. The following redox balance components were evaluated: catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (FRAP), NADPH oxidase (NOX), nitric oxide synthase (NOS), hydrogen peroxide (H2O2), and the tissue bioavailability of nitric oxide (NO) such as S-nitrosothiol (RSNO) and nitrite (NO2−). The results indicated a process of renoprotection in both kidneys, indicated by the reduction of cellular damage and some oxidant agents. We also observed an increase in the activity of antioxidant enzymes, such as SOD, and an increase in NO bioavailability. In the heart, we noticed an increase in the activity of NOX and NOS, together with increased cell damage on day 8, followed by a reduction in protein damage on day 15. The present study concludes that the kidneys and heart undergo distinct processes of damage and repair at the analyzed times, since the heart is a secondary target of ischemic kidney injury. These results are important for a better understanding of the cellular mechanisms involved in CRS.

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Section: Discussionmentioning

confidence: 99%

Characterization of the Oxidative Stress in Renal Ischemia/Reperfusion-Induced Cardiorenal Syndrome Type 3

Caio‐Silva

Dias

Junho

et al. 2020

BioMed Research International

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“…Although tremendous progress has been made in exploring the molecular mechanisms and signaling pathways of CKD in recent years, the event that initiates this process has not been elucidated. Studies have confirmed that hypertension, proteinuria, obesity, diabetes, and dyslipidemia (Richter et al, 2015;Amador-Martinez et al, 2019;Ku et al, 2019) can lead to progressive fibrosis, which generally refers to the excessive deposition of extracellular matrix components in the tubulointerstitium, resulting in the loss of renal function during CKD. Angiotensin II (Ang II) plays a critical role in hypertension-induced fibrogenic mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Contribution of TGF-Beta-Mediated NLRP3-HMGB1 Activation to Tubulointerstitial Fibrosis in Rat With Angiotensin II-Induced Chronic Kidney Disease

Zhang

Fan

Cai

et al. 2020

Front. Cell Dev. Biol.

163

130

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Fibrosis is a common phenotype that often leads to the progression of blood pressure-induced chronic kidney disease (CKD). TGF-beta plays an important role in promoting pathogenesis, and NLRP3 is a critical mediator in the progression of blood pressure-induced CKD. However, the pathophysiological roles of the TGF-betamediated NLRP3 pathway in modulating fibrosis in blood pressure-induced CKD have not been elucidated. The present study aims to investigate the contribution of TGFbeta-mediated NLRP3 inflammasome to renal fibrosis in rats with high blood pressure. By treating rats with angiotensin II (Ang II) for 14 days, we observed the development of fibrosis, characterized by epithelial-mesenchymal transition (EMT) markers [alphasmooth muscle actin (alpha-SMA), MMP-2, and MMP-9]. Immunohistochemical analysis further revealed that TGF-beta and NLRP3 inflammasome activation [high-mobility group box 1 (HMGB1), IL-1beta, and NLRP3] were significantly upregulated in the kidney of rats with Ang II-induced hypertension. Interestingly, we observed that Ang II could not increase the production of NLRP3 proteins, but TGF-beta could induce NLRP3 protein expression in cultured NRK-52E cells. Furthermore, we speculated that TGF-beta played a pathogenic role in Ang II-induced CKD because TGF-beta induced the activation of NLRP3 inflammasomes and Gasdermin D cleavage expression. We also proved that the pharmacological inhibition of NLRP3 by ISO caused a decrease in TGF-beta-induced NLRP3 inflammasome activation and the expression of EMT markers (alpha-SMA and CollagenI) and Gasdermin D cleavage. Collectively, these results suggest that TGF-beta-mediated NLRP3 inflammasome activation may cause the release of HMGB1 and an increase in Gasdermin D cleavage in NRK-52E, thereby contributing to renal fibrosis in Ang II-induced CKD. These findings provide novel insights into the pathogenic role of NLRP3 in CKD associated with high blood pressure.

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“…34 Chronic kidney disease (CKD) is a major contributor to cardiovascular (CV) mortality. 35 As the renal disease worsens, there is element of cardiac hypertrophy and fibrosis. This has been attributed to oxidative stress and reduced nitric oxide availability in cardiac myocytes.…”

Section: Discussionmentioning

confidence: 99%

Chronic kidney disease in pregnancy and fetomaternal outcome

Gupta

Chawla

Ara

et al. 2019

Int J Reprod Contracept Obstet Gynecol

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Background: Chronic kidney disease is a heterogeneous group of renal dysfunctions with complex and varied presentations in pregnancy. With a long asymptomatic course, timely diagnosis and management is crucial for fetomaternal wellbeing.Methods: A retrospective cohort study over a period of 3 years and 4 months included all obstetric in patients with known or newly diagnosed renal disorders. Maternal outcome was measured with regard to biochemical parameters presence /absence of proteinuria, hypertension, mode of pregnancy termination and complications. Fetal outcome was noted with respect to antenatal complications, weight, Apgar, NICU stay. Computation of results was done using percentages, mean and proportions.Results: Out of 13 women studied, 53.8% were pre-diagnosed cases of renal dysfunction and 46.2% were diagnosed during pregnancy. 38% had proteinuria at first visit and 50% remained so even after delivery. 60% had history of pregnancy induced hypertension in their previous pregnancies. Secondary hypertension and superimposed preeclampsia were seen in 30% and 38% cases respectively, with only one patient requiring magnesium sulphate prophylaxis in post-partum. Cardiac dysfunction was found to be coexisting in 15.3% cases with pre-existing renal leision. Intrauterine growth restriction was seen in 61.5% cases Average fetal weight was 2. 26kg with 30% having NICU stay. 30.6% had preterm delivery. Mode of delivery was caesarean section in 46% cases.Conclusions: Pregnancy with CKD is a high-risk pregnancy with adverse fetomaternal outcomes. For optimal pregnancy outcomes, an expert multidisciplinary team is required. With limited studies in south Asian population, there needs to be an upgradation in registry system.

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Reduced endothelial nitric oxide synthase activation contributes to cardiovascular injury during chronic kidney disease progression

Cited by 31 publications

References 46 publications

Characterization of the Oxidative Stress in Renal Ischemia/Reperfusion-Induced Cardiorenal Syndrome Type 3

Characterization of the Oxidative Stress in Renal Ischemia/Reperfusion-Induced Cardiorenal Syndrome Type 3

Contribution of TGF-Beta-Mediated NLRP3-HMGB1 Activation to Tubulointerstitial Fibrosis in Rat With Angiotensin II-Induced Chronic Kidney Disease

Chronic kidney disease in pregnancy and fetomaternal outcome

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