Small Vessels, Big Role

Chade, Alejandro

doi:10.1161/hypertensionaha.116.08319

Cited by 29 publications

(14 citation statements)

References 148 publications

(197 reference statements)

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“…42 Therefore, endothelial dysfunction could be an early-stage manifestation of MetS and related diseases and could have a causal role in the development of organ failure and/or CKD. 43 Increases in AGE levels were not observed in the kidney of 20 weeks HFD-induced MetS rats. Since we have previously shown that serum and liver AGEs levels are increased in animals with MetS 20 it is plausible to think that macrophages and kupffer cells from the liver are actively participating in AGEs detoxification, generating low molecular weight soluble peptides which are further excreted by the kidneys.…”

Section: Discussionmentioning

confidence: 93%

<p>High-fat diet-induced kidney alterations in rats with metabolic syndrome: endothelial dysfunction and decreased antioxidant defense</p>

Silvares

Pereira

Flores

et al. 2019

DMSO

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This study aimed to investigate changes in renal function and the AGE-RAGE axis in the kidney of a non-genetic animal model of metabolic syndrome (MetS) induced by high-fat diet (HFD). Additionally, we evaluated the protective effect of pyridoxamine (PM), a vitamin B6 analog with anti-AGE effects, in the context of diet-related renal endothelial dysfunction. Methodology: In Wistar rats, the MetS animal model was induced by 20 or 28 weeks of HFD feeding. When indicated, a subgroup of animals was treated daily with PM (60 mg/kg) for 2 months. Tissue perfusion in renal microcirculation was examined by laser speckle contrast imaging. Oxidative stress was analyzed by thiobarbituric acid reactive species and the inflammatory markers by ELISA (TNF-α and IL-1β). Reverse transcription polymerase chain reaction was used to analyze eNOs, IL-6, vascular cell adhesion molecule (VCAM), NADPH oxidase subunit 47 (N47), catalase, and receptor for AGE (RAGE) gene expression. Results: Wistar rats fed a HFD showed negligible alteration in renal function, decrease in catalase mRNA transcripts and catalase enzyme activity compared to control (CTL) animals. Increased levels of IL-1β were observed in the kidney of MetS-induced rats. HFD-fed rats exhibited kidney endothelial dysfunction, with no significant differences in basal microvascular blood flow. PM significantly improved kidney vasorelaxation in HFD-fed rats. eNOS, VCAM, and RAGE gene expression and AGE content were not altered in kidneys of HFDinduced MetS rats in comparison to CTLs. Conclusions: Our findings suggest that HFD-induced microvascular dysfunction precedes the decline in renal function, and could be related to antioxidant machinery defects and inflammation activation in the kidney. PM showed a vasoprotective effect, and thus, could be an important contributory factor in ameliorating diet-induced renal damage.

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Section: Discussionmentioning

confidence: 93%

<p>High-fat diet-induced kidney alterations in rats with metabolic syndrome: endothelial dysfunction and decreased antioxidant defense</p>

Silvares

Pereira

Flores

et al. 2019

DMSO

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“…Common kidney diseases include acute kidney injury (AKI), chronic kidney disease (CKD), diabetic nephropathy (DN), lupus nephritis, and hypertensive nephropathy, induced by various causes. The main therapeutic methods against these kidney diseases include drug therapy, dialysis, and kidney transplantation [ 2 , 3 ]; however, new therapies emerge due to the limitations of drug therapy, inconvenience of dialysis, and shortage of donors for kidney transplantation [ 4 ]. In recent years, stem cells, as a new regenerative therapy, have been used to treat numerous diseases, including kidney diseases [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cells and extracellular vesicles in therapy against kidney diseases

Huang

Yang

2021

Stem Cell Res Ther

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Kidney diseases pose a threat to human health due to their rising incidence and fatality rate. In preclinical and clinical studies, it has been acknowledged that mesenchymal stem cells (MSCs) are effective and safe when used to treat kidney diseases. MSCs play their role mainly by secreting trophic factors and delivering extracellular vesicles (EVs). The genetic materials and proteins contained in the MSC-derived EVs (MSC-EVs), as an important means of cellular communication, have become a research focus for targeted therapy of kidney diseases. At present, MSC-EVs have shown evident therapeutic effects on acute kidney injury (AKI), chronic kidney disease (CKD), diabetic nephropathy (DN), and atherosclerotic renovascular disease (ARVD); however, their roles in the transplanted kidney remain controversial. This review summarises the mechanisms by which MSC-EVs treat these diseases in animal models and proposes certain problems, expecting to facilitate corresponding future clinical practice.

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“…Studies from pre-clinical and clinical settings showed that renal microvascular rarefaction, both functional and structural, is a universal pathological feature of CKD that may start early in prominent cardiovascular and renal risk factors like hypertension, diabetes, or obesity and may often predict decline in renal function 12– 18 . Pre-clinical studies also show that ARVD induces a significant and often progressive remodeling and loss of the microvasculature distal to the stenosis, paired with blunted renal mechanisms of microvascular repair and angiogenesis 19, 20 . The progressive microvascular injury is the result of combined insults such as renal ischemia, systemic and renal inflammation, and consequent pro-fibrotic and pro-apoptotic activity that develops in the kidney, often independently of the severity of renal artery stenosis but exacerbated when several cardiovascular risk factors coexist 21, 22 .…”

Section: Trying To Fix Some Of the Bumpsmentioning

confidence: 99%

Understanding and managing atherosclerotic renovascular disease: still a work in progress

Chade

2018

F1000Res

Self Cite

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Atherosclerotic renovascular disease (ARVD) is an unresolved therapeutic dilemma despite extensive pre-clinical and clinical studies. The pathophysiology of the disease has been widely studied, and many factors that may be involved in progressive renal injury and cardiovascular risk associated with ARVD have been identified. However, therapies and clinical trials have focused largely on attempts to resolve renal artery stenosis without considering the potential need to treat the renal parenchyma beyond the obstruction. The results of these trials show a staggering consistence: although nearly 100% of the patients undergoing renal angioplasty show a resolution of the vascular obstruction, they do not achieve significant improvements in renal function or blood pressure control compared with those patients receiving medical treatment alone. It seems that we may need to take a step back and reconsider the pathophysiology of the disease in order to develop more effective therapeutic strategies. This mini-review discusses potential therapeutic alternatives that focus on the renal parenchyma distal to the vascular obstruction and may provide additional tools to enhance current treatment of ARVD.

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Small Vessels, Big Role

Cited by 29 publications

References 148 publications

<p>High-fat diet-induced kidney alterations in rats with metabolic syndrome: endothelial dysfunction and decreased antioxidant defense</p>

<p>High-fat diet-induced kidney alterations in rats with metabolic syndrome: endothelial dysfunction and decreased antioxidant defense</p>

Mesenchymal stem cells and extracellular vesicles in therapy against kidney diseases

Understanding and managing atherosclerotic renovascular disease: still a work in progress

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