Indoxyl sulfate impairs valsartan-induced neovascularization

Publication date: Available online 14 January 2020Source: Redox BiologyAuthor(s): Ko-Lin Kuo, Jin-Feng Zhao, Po-Hsun Huang, Bei-Chia Guo, Der-Cherng Tarng, Tzong-Shyuan LeeAbstractStudies revealed that the use of renin-angiotensin-aldosterone system antagonism is not associated with a statistically significant reduction in the risk of cardiovascular events in patients with chronic kidney disease (CKD) compared with that in the general population. We tested the hypothesis that indoxyl sulfate (IS) can interfere with the protective effect of valsartan-mediated on endothelial function in vitro and neovascularization in mice underwent subtotal nephrectomy. In human aortic endothelial cells, we first demonstrated that IS impaired the valsartan-mediated phosphorylation of eNOSThr495, nitric oxide production and tube formation via NADPH oxidase (NOX) and protein kinase C (PKC) phosphorylation, but this effect was suppressed by cotreatment with apocynin and calphostin C. In vivo, IS attenuated valsartan-induced angiogenesis in Matrigel plugs in mice. Moreover, in subtotal nephrectomy mice who underwent hindlimb ischemic surgery, valsartan significantly increased the mobilization of endothelial progenitor cells in circulation as well as the reperfusion of blood flow and density of CD31+ capillaries in ischemic limbs. However, IS attenuated the protective effect of valsartan-induced neovascularization and increased the expression of p-PKCαSer657 and p-eNOSThr497 in ischemic limbs...
Source: Redox Biology - Category: Biology Source Type: research

Related Links:

Publication date: Available online 8 February 2020Source: Chemico-Biological InteractionsAuthor(s): Chih-Ying Changchien, Meng-Ho Sung, Hsin-Han Chang, Wen-Chiuan Tsai, Yu-Sen Peng, Ying ChenAbstractHeart rhythm disturbances have been widely recognized as major triggers of cardiovascular (CV) mortality in chronic kidney disease (CKD) patients. Connexin 43 (Cx43)-composed gap junctions are essential in cardiomyocyte synchronization and may be involved in the pathological response to uremic toxins. Indoxyl sulfate (IS) is one of the most dominant uremic toxins that contribute to CKD-related cardiovascular diseases. In primar...
Source: Chemico Biological Interactions - Category: Biochemistry Source Type: research
Abstract Heart rhythm disturbances have been widely recognized as major triggers of cardiovascular (CV) mortality in chronic kidney disease (CKD) patients. Connexin 43 (Cx43)-composed gap junctions are essential in cardiomyocyte synchronization and may be involved in the pathological response to uremic toxins. Indoxyl sulfate (IS) is one of the most dominant uremic toxins that contribute to CKD-related cardiovascular diseases. In primary cultures of rat neonatal cardiomyocytes, we demonstrated that IS treatment decreased spontaneous contraction without impairing viability. In addition, there was disruption of gap ...
Source: Chemico-Biological Interactions - Category: Molecular Biology Authors: Tags: Chem Biol Interact Source Type: research
Conclusion: These findings improve understanding of the role of elevated CHGA in the progression of CKD and reveal novel pathways that could be exploited for therapeutic strategies in hypertensive kidney disease.
Source: Journal of Hypertension - Category: Cardiology Tags: ORIGINAL PAPERS: Organ damage Source Type: research
Abstract OBJECTIVES: Surgically treated clinical T1 (cT1) kidney cancer has in general a good prognosis, but there is a risk of upstaging that can potentially jeopardize the oncological outcomes after partial nephrectomy (PN). Aim of this study is to analyze the outcomes of robot-assisted PN (RAPN) for cT1 kidney cancer upstaged to pT3a, and to identify predictors of upstaging. MATERIAL AND METHODS: The study cohort included 1,640 cT1 patients who underwent RAPN between 2005 and 2018 at 10 academic institutions. Multivariate logistic regression model was used to assess the predictors of upstaging. Kaplan-Mei...
Source: Urologic Oncology - Category: Urology & Nephrology Authors: Tags: Urol Oncol Source Type: research
CONCLUSION: We propose a role for systematically incorporating APOL1 genotyping in the evaluation and informed consent process of potential AA donors while acknowledging the controversial considerations associated with it. PMID: 31940609 [PubMed - as supplied by publisher]
Source: American Journal of Nephrology - Category: Urology & Nephrology Authors: Tags: Am J Nephrol Source Type: research
Conclusions. Transplant physicians should inform potential living kidney donors at risk for APOL1-associated nephropathy about the gene and possibility of genetic testing early in the donor evaluation, well before scheduling the donor nephrectomy. Transplant programs must weigh risks of performing a donor nephrectomy in those with 2 APOL1 renal risk variants (high-risk genotypes), particularly younger individuals. Our program counsels kidney donors with APOL1 high-risk genotypes in the same fashion as with risk genotypes in other nephropathy genes. Because most African American kidney donor candidates lacking hypertensio...
Source: Transplantation - Category: Transplant Surgery Tags: Reviews Source Type: research
Abstract BACKGROUND: Chronic kidney disease (CKD) models are known to study pathophysiology and various treatment methods. Renal dysfunction could influence erythrocytes through several pathways. However, hemorheological and microcirculatory relation of CKD models are not completely studied yet. OBJECTIVE: To evaluate erythrocyte micro-rheology, microcirculatory and structural compensatory mechanisms in a rat model of CKD. METHODS: Female Sprague-Dawley rats were subjected to nephrectomy group (NG, n = 6) or sham-operated group (SG, n = 6). NG rats were subjected to 5/6 nephrectomy in two stages....
Source: Clinical Hemorheology and Microcirculation - Category: Hematology Authors: Tags: Clin Hemorheol Microcirc Source Type: research
Prognostic value of connective tissue growth factor and c-Myb expression in IgA nephropathy and Henoch-Schönlein purpura-A pilot immunohistochemical study. Acta Histochem. 2019 Dec 20;:151479 Authors: Mizdrak M, Filipović N, Vukojević K, Čapkun V, Mizdrak I, Durdov MG Abstract AIM: Adverse and advanced prognostic signs in IgA nephropathy (IgAN) are interstitial fibrosis and tubular atrophy, but early predictors of bad outcome are still lacking. We investigated expression of connective tissue growth factor (CTGF) and c-Myb in renal biopsies of IgAN and Henoch-Schönlein purpura (HSP), becau...
Source: Acta Histochemica - Category: Biochemistry Authors: Tags: Acta Histochem Source Type: research
In this study, we investigated whether HIF activation has a beneficial effect on kidney and cardiovascular outcomes in the remnant kidney model. We used the 5/6 nephrectomy model with a nitric oxide synthase inhibitor Nω-nitro-L-arginine (L-NNA, 20 mg/L in the drinking water). Rats received diet with 0.005% enarodustat (PHD inhibitor) or vehicle for 8 weeks starting 2 week prior to the 5/6 nephrectomy. Activation of HIF by the PHD inhibitor reduced cardiac hypertrophy and ameliorated myocardial fibrosis in association with restored capillary density and improvement in mitochondrial morphology. In regard to kidneys, e...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research
Authors: Brassetti A, Anceschi U, Bertolo R, Ferriero M, Tuderti G, Capitanio U, Larcher A, Garisto J, Antonelli A, Mottire A, Minervini A, Dell'oglio P, Veccia A, Amparore D, Flammia RS, Mari A, Porpiglia F, Montorsi F, Kaouk J, Autorino R, Carini M, Gallucci M, Simone G Abstract BACKGROUND: To improve standard reporting of outcomes after partial nephrectomy, different "Trifecta" systems have been conceived. The subjective assessment of the included parameters and the unreliability for off-clamp procedures limited their reproducibility; their role in predicting functional and oncologic outcomes has never...
Source: Minerva Urologica e Nefrologica - Category: Urology & Nephrology Tags: Minerva Urol Nefrol Source Type: research
More News: Biology | Cardiology | Cardiovascular | Cardiovascular & Thoracic Surgery | Chia | Chronic Kidney Disease | Diovan | Heart | Nephrectomy | Statistics | Study | Urology & Nephrology