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1.
Clin Kidney J ; 16(8): 1278-1287, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37529650

RESUMO

Background: Endothelial damage and cardiovascular disease complicate chronic kidney disease (CKD). The increased atherogenicity observed in patients with CKD can be linked to microinflammation and endothelial damage. Circulating endothelial glycocalyx degradation products, such as perlecan and decorin, tend to be elevated in CKD. We aimed to explore the association between the plasma perlecan and decorin levels and this pro-inflammatory and atherogenic state by studying monocyte subpopulations and intracellular adhesion molecule (ICAM)-1 expression in patients with CKD. Methods: We studied 17 healthy controls, 23 patients with advanced CKD, 25 patients on haemodialysis, 23 patients on peritoneal dialysis and 20 patients who underwent kidney transplantation. Perlecan and decorin levels were evaluated using enzyme-linked immunosorbent assays, and the monocyte phenotype was analysed using direct immunofluorescence and flow cytometry. Results: The plasma perlecan levels were higher in patients with CKD than in the healthy controls. These levels were associated with a higher prevalence of ICAM-1+ monocytes. Conversely, patients with advanced CKD (pre-dialysis) had higher plasma decorin levels, which were associated with a reduced ICAM-1 expression per monocyte. Conclusions: Elevated perlecan levels in CKD may be associated with a higher prevalence of ICAM-1+ monocytes and a pro-inflammatory phenotype. Elevated decorin levels may act as a negative regulator of ICAM-1 expression in monocytes. Therefore, perlecan and decorin may be related to inflammation and monocyte activation in CKD and may act as potential markers of endothelial damage.

2.
Nefrologia (Engl Ed) ; 43(1): 63-80, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37268501

RESUMO

Chronic kidney disease (CKD) is a pathology with a high worldwide incidence and an upward trend affecting the elderly. When CKD is very advanced, the use of renal replacement therapies is required to prolong its life (dialysis or kidney transplantation). Although dialysis improves many complications of CKD, the disease does not reverse completely. These patients present an increase in oxidative stress, chronic inflammation and the release of extracellular vesicles (EVs), which cause endothelial damage and the development of different cardiovascular diseases (CVD). CKD patients develop premature diseases associated with advanced age, such as CVD. EVs play an essential role in developing CVD in patients with CKD since their number increases in plasma and their content is modified. The EVs of patients with CKD cause endothelial dysfunction, senescence and vascular calcification. In addition, miRNAs free or transported in EVs together with other components carried in these EVs promote endothelial dysfunction, thrombotic and vascular calcification in CKD, among other effects. This review describes the classic factors and focuses on the role of new mechanisms involved in the development of CVD associated with CKD, emphasizing the role of EVs in the development of cardiovascular pathologies in the context of CKD. Moreover, the review summarized the EVs' role as diagnostic and therapeutic tools, acting on EV release or content to avoid the development of CVD in CKD patients.


Assuntos
Doenças Cardiovasculares , MicroRNAs , Insuficiência Renal Crônica , Calcificação Vascular , Humanos , Idoso , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/epidemiologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/diagnóstico , Calcificação Vascular/etiologia , Calcificação Vascular/patologia , Inflamação
3.
Mech Ageing Dev ; 211: 111797, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36868323

RESUMO

Sexual dimorphism is a key factor to consider in the ageing process given the impact that it has on life expectancy. The oxidative-inflammatory theory of ageing states that the ageing process is the result of the establishment of oxidative stress which, due to the interplay of the immune system, translates into inflammatory stress, and that both processes are responsible for the damage and loss of function of an organism. We show that there are relevant gender differences in a number of oxidative and inflammatory markers and propose that they may account for the differential lifespan between sexes, given that males display, in general, higher oxidation and basal inflammation. In addition, we explain the significant role of circulating cell-free DNA as a marker of oxidative damage and an inductor of inflammation, connecting both processes and having the potential to become a useful ageing marker. Finally, we discuss how oxidative and inflammatory changes take place differentially with ageing in each sex, which could also have an impact on the sex-differential lifespan. Further research including sex as an essential variable is needed to understand the grounds of sex differences in ageing and to better comprehend ageing itself.


Assuntos
Envelhecimento , Caracteres Sexuais , Feminino , Humanos , Masculino , Fatores Sexuais , Longevidade/genética , Inflamação
4.
Nefrología (Madrid) ; 43(1): 63-80, ene.-feb. 2023. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-215242

RESUMO

La enfermedad renal crónica (ERC) tiene una alta incidencia mundial y una tendencia ascendente que afecta principalmente a personas de edad avanzada. Cuando la ERC está muy avanzada se requiere el uso de terapias renales sustitutivas para prolongar la vida (diálisis o trasplante renal) y, pese a que la diálisis mejora muchas complicaciones de la ERC, la enfermedad no revierte de manera completa. Estos pacientes presentan un aumento del estrés oxidativo, inflamación crónica y aumento de la liberación de vesículas extracelulares (VE), que provocan daño endotelial y el desarrollo de distintas enfermedades cardiovasculares (ECV). De hecho, los pacientes con ERC desarrollan de forma prematura enfermedades asociadas a una edad avanzada, como es el caso de las ECV. Las VE desempeñan un papel muy importante en el desarrollo de ECV en pacientes con ERC, ya que su número aumenta en el plasma y su contenido se modifica. Las VE de pacientes con ERC generan disfunción endotelial, senescencia y calcificación vascular. Además, los miRNA libres o transportados en las VE junto a otros componentes vehiculados en estas VE promueven disfunción endotelial, eventos trombóticos y calcificación vascular en los pacientes con ERC, entre otros efectos. En esta revisión se describen los factores clásicos y el papel de nuevos mecanismos que intervienen en el desarrollo de la ECV asociada a la ERC, con especial hincapié en el papel de las VE en el desarrollo de enfermedades cardiovasculares en un contexto de ERC. Además, se expone el papel de las VE como herramienta diagnóstica y como diana terapéutica, actuando sobre su liberación o contenido para intentar evitar el desarrollo de ECV en enfermos renales crónicos. (AU)


Chronic kidney disease (CKD) is a pathology with a high worldwide incidence and an upward trend affecting the elderly. When CKD is very advanced, the use of renal replacement therapies is required to prolong its life (dialysis or kidney transplantation). Although dialysis improves many complications of CKD, the disease does not reverse completely. These patients present an increase in oxidative stress, chronic inflammation and the release of extracellular vesicles (EVs), which cause endothelial damage and the development of different cardiovascular diseases (CVD). CKD patients develop premature diseases associated with advanced age, such as CVD. EVs play an essential role in developing CVD in patients with CKD since their number increases in plasma and their content is modified. The EVs of patients with CKD cause endothelial dysfunction, senescence and vascular calcification. In addition, miRNAs free or transported in EVs together with other components carried in these EVs promote endothelial dysfunction, thrombotic and vascular calcification in CKD, among other effects. This review describes the classic factors and focuses on the role of new mechanisms involved in the development of CVD associated with CKD, emphasizing the role of EVs in the development of cardiovascular pathologies in the context of CKD. Moreover, the review summarized the EVs’ role as diagnostic and therapeutic tools, acting on EV release or content to avoid the development of CVD in CKD patients. (AU)


Assuntos
Humanos , Insuficiência Renal Crônica , Doenças Cardiovasculares , Calcificação Vascular , Vesículas Extracelulares
5.
J Pers Med ; 12(2)2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35207703

RESUMO

Atherosclerosis is probably one of the paradigms of disease linked to aging. Underlying the physiopathology of atherosclerosis are cellular senescence, oxidative stress, and inflammation. These factors are increased in the elderly and from chronic disease patients. Elevated levels of oxidative stress affect cellular function and metabolism, inducing senescence. This senescence modifies the cell phenotype into a senescent secretory phenotype. This phenotype activates immune cells, leading to chronic systemic inflammation. Moreover, due to their secretory phenotype, senescence cells present an increased release of highlighted extracellular vesicles that will change nearby/neighborhood cells and paracrine signaling. For this reason, searching for specific senescent cell biomarkers and therapies against the development/killing of senescent cells has become relevant. Recently, senomorphic and senolityc drugs have become relevant in slowing down or eliminating senescence cells. However, even though they have shown promising results in experimental studies, their clinical use is still yet to be determined.

6.
Front Med (Lausanne) ; 8: 705159, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646838

RESUMO

Kidney transplantation is the best option for patients with end-stage renal disease. Despite the improvement in cardiovascular burden (leading cause of mortality among patients with chronic kidney disease), cardiovascular adverse outcomes related to the inflammatory process remain a problem. Thus, the aim of the present study was to characterize the immune profile and microvesicles of patients who underwent transplantation. We investigated the lymphocyte phenotype (CD3, CD4, CD8, CD19, and CD56) and monocyte phenotype (CD14, CD16, CD86, and CD54) in peripheral blood, and endothelium-derived microvesicles (annexin V+CD31+CD41-) in plasma of patients with advanced chronic kidney disease (n = 40), patients with transplantation (n = 40), and healthy subjects (n = 18) recruited from the University Hospital "12 de Octubre" (Madrid, Spain). Patients with kidney transplantation had B-cell lymphopenia, an impairment in co-stimulatory (CD86) and adhesion (CD54) molecules in monocytes, and a reduction in endothelium-derived microvesicles in plasma. The correlations between those parameters explained the modifications in the expression of co-stimulatory and adhesion molecules in monocytes caused by changes in lymphocyte populations, as well as the increase in the levels of endothelial-derived microvesicles in plasma caused by changes in lymphocyte and monocytes populations. Immunosuppressive treatment could directly or indirectly induce those changes. Nevertheless, the particular characteristics of these cells may partly explain the persistence of cardiovascular and renal alterations in patients who underwent transplantation, along with the decrease in arteriosclerotic events compared with advanced chronic kidney disease. In conclusion, the expression of adhesion molecules by monocytes and endothelial-derived microvesicles is related to lymphocyte alterations in patients with kidney transplantation.

7.
Antioxidants (Basel) ; 10(7)2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34356387

RESUMO

Oxidative stress plays a key role in the pathophysiology of chronic kidney disease (CKD). Most studies have investigated peripheral redox state focus on plasma, but not in different immune cells. Our study analyzed several redox state markers in plasma and isolated peripheral polymorphonuclear (PMNs) and mononuclear (MNs) leukocytes from advanced-CKD patients, also evaluating differences of hemodialysis (HD) and peritoneal dialysis (PD) procedures. Antioxidant (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH)) and oxidant parameters (xanthine oxidase (XO), oxidized glutathione (GSSG), malondialdehyde (MDA)) were assessed in plasma, PMNs and MNs from non-dialysis-dependent-CKD (NDD-CKD), HD and PD patients and healthy controls. Increased oxidative stress and damage were observed in plasma, PMNs and MNs from NDD-CKD, HD and PD patients (increased XO, GSSG and MDA; decreased SOD, CAT, GPX and GSH; altered GSSG/GSH balance). Several oxidative alterations were more exacerbated in PMNs, whereas others were only observed in MNs. Dialysis procedures had a positive effect on preserving the GSSG/GSH balance in PMNs. Interestingly, PD patients showed greater oxidative stress than HD patients, especially in MNs. The assessment of redox state parameters in PMNs and MNs could have potential use as biomarkers of the CKD progression.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34360333

RESUMO

Over the last hundred years, life expectancy in developed countries has increased because of healthier living habits and the treatment of chronic pathologies causing premature aging. Aging is an inexorable, time-dependent, multifactorial process characterized by a series of progressive and irreversible physiological changes associated with loss of functional, psychological, and social capabilities. Numerous factors, such as oxidative stress, inflammation, and cellular senescence, and an irreversible geriatric syndrome known as frailty, contribute to human body deterioration in aging. The speed of aging may differ between individuals depending on the presence or absence of multiple factors (genetic and/or environment) and the subsequent misbalance of homeostasis, together with the increase of frailty, which also plays a key role in developing chronic diseases. In addition, pathological circumstances have been reported to precipitate or accelerate the aging process. This review investigated the mechanisms involved in the developing pathologies, particularly chronic kidney disease, associated with aging.


Assuntos
Senilidade Prematura , Fragilidade , Insuficiência Renal Crônica , Idoso , Envelhecimento , Fragilidade/epidemiologia , Humanos , Inflamação , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia
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