Novel Insights Into the Role of Glycans in the Pathophysiology of Glomerular Endotheliosis in Preeclampsia

Galvis-Ramírez, M. F.; Castillo, Juan Carlos Quintana; Bueno-Sánchez, Julio César

doi:10.3389/fphys.2018.01470

Cited by 15 publications

(39 citation statements)

References 93 publications

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“…In various disease conditions, a decrease in N ‐ and 6‐ O ‐sulfate domains in biopsies from patients were associated with albuminuria 17,72,77 . Inflammatory diseases with different etiology may promote EnGL dysfunction by several associated pathways and initiate albuminuria 17 . Intensive care unit (ICU)‐treated COVID‐19 patients with AKI frequently presented with albuminuria 103,104 …”

Section: Glycocalyx and Sulfationmentioning

confidence: 99%

Pathogenesis of COVID‐19 described through the lens of an undersulfated and degraded epithelial and endothelial glycocalyx

et al. 2021

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The glycocalyx surrounds every eukaryotic cell and is a complex mesh of proteins and carbohydrates. It consists of proteoglycans with glycosaminoglycan side chains, which are highly sulfated under normal physiological conditions. The degree of sulfation and the position of the sulfate groups mainly determine biological function. The intact highly sulfated glycocalyx of the epithelium may repel severe acute respiratory syndrome‐related coronavirus 2 (SARS‐CoV‐2) through electrostatic forces. However, if the glycocalyx is undersulfated and 3‐O‐sulfotransferase 3B (3OST‐3B) is overexpressed, as is the case during chronic inflammatory conditions, SARS‐CoV‐2 entry may be facilitated by the glycocalyx. The degree of sulfation and position of the sulfate groups will also affect functions such as immune modulation, the inflammatory response, vascular permeability and tone, coagulation, mediation of sheer stress, and protection against oxidative stress. The rate‐limiting factor to sulfation is the availability of inorganic sulfate. Various genetic and epigenetic factors will affect sulfur metabolism and inorganic sulfate availability, such as various dietary factors, and exposure to drugs, environmental toxins, and biotoxins, which will deplete inorganic sulfate. The role that undersulfation plays in the various comorbid conditions that predispose to coronavirus disease 2019 (COVID‐19), is also considered. The undersulfated glycocalyx may not only increase susceptibility to SARS‐CoV‐2 infection, but would also result in a hyperinflammatory response, vascular permeability, and shedding of the glycocalyx components, giving rise to a procoagulant and antifibrinolytic state and eventual multiple organ failure. These symptoms relate to a diagnosis of systemic septic shock seen in almost all COVID‐19 deaths. The focus of prevention and treatment protocols proposed is the preservation of epithelial and endothelial glycocalyx integrity.

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Section: Glycocalyx and Sulfationmentioning

confidence: 99%

Pathogenesis of COVID‐19 described through the lens of an undersulfated and degraded epithelial and endothelial glycocalyx

et al. 2021

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“…There is evidence of unchanged ( Table 2, line 8, 9, 20) endocan contents, which may be due to specific characteristics of cohorts [42] and the paucity of the PE group [43]. Third, the urinary GAGs excretion and its increased urine contents (Table 2, line 2) were revealed in patients with PE and linked with decreased HSPGs (heparan sulfate proteoglycans) and CSPGs (chondroitin sulfate proteoglycans) contents in the glomerular basement membrane (GMB); this will disrupt the macromolecular organization of the GMB architecture with concomitant permeability changes and functional disorder of the GMB, thus leading to increased proteinuria [44,45]. Case-control study Lectin histochemistry…”

Section: Regulation Of Interactions Of Blood Cells With the Vascular mentioning

confidence: 99%

Can Endothelial Glycocalyx Be a Major Morphological Substrate in Pre-Eclampsia?

Ziganshina

Yarotskaya

Bovin

et al. 2020

IJMS

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Today pre-eclampsia (PE) is considered as a disease of various theories; still all of them agree that endothelial dysfunction is the leading pathogenic factor. Endothelial dysfunction is a sequence of permanent immune activation, resulting in the change of both the phenotype and the functions of an endothelial cell and of the extracellular layer associated with the cell membrane—endothelial glycocalyx (eGC). Numerous studies demonstrate that eGC mediates and regulates the key functions of endothelial cells including regulation of vascular tone and thromboresistance; and these functions are disrupted during PE. Taking into account that eGC and its components undergo alterations under pathological conditions leading to endothelial activation, it is supposed that eGC plays a certain role in pathogenesis of PE. Envisaging the eGC damage as a key factor of PE, might be a new approach to prevention, treatment, and rehabilitation of patients with PE. This approach could include the development of drugs protecting eGC and promoting regeneration of this structure. Since the issue of PE is far from being solved, any effort in this direction might be valuable.

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“…In the present study, the histological findings were not the typical findings reported in PE 36,40 except for the basement membrane thickening, fusion of foot processes and mesangial expansion 40,41 . However, the changes do indicate damage to the glomerular filtration barrier, which compromises renal function 40,42 . In general changes in oncotic pressure might significantly affect blood volume regulation and therefore the blood pressure in a normal physiological response 43 .…”

Section: Discussionmentioning

confidence: 99%

Pregnant alpha-1-microglobulin (A1M) knockout mice exhibit features of kidney and placental damage, hemodynamic changes and intrauterine growth restriction

Aleksenko

Åkerström

Hansson

et al. 2020

Sci Rep

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Alpha-1-microglobulin (A1M) is an antioxidant previously shown to be elevated in maternal blood during pregnancies complicated by preeclampsia and suggested to be important in the endogenous defense against oxidative stress. A knockout mouse model of A1M (A1Mko) was used in the present study to assess the importance of A1M during pregnancy in relation to the kidney, heart and placenta function. Systolic blood pressure (SBP) and heart rate (HR) were determined before and throughout gestation. The morphology of the organs was assessed by both light and electron microscopy. Gene expression profiles relating to vascular tone and oxidative stress were analyzed using RT-qPCR with validation of selected gene expression relating to vascular tone and oxidative stress response. Pregnant age-matched wild type mice were used as controls. In the A1Mko mice there was a significantly higher SBP before pregnancy that during pregnancy was significantly reduced compared to the control. In addition, the HR was higher both before and during pregnancy compared to the controls. Renal morphological abnormalities were more frequent in the A1Mko mice, and the gene expression profiles in the kidney and the heart showed downregulation of transcripts associated with vasodilation. Simultaneously, an upregulation of vasoconstrictors, blood pressure regulators, and genes for osmotic stress response, ion transport and reactive oxygen species (ROS) metabolism occurred. Fetal weight was lower in the A1Mko mice at E17.5. The vessels in the labyrinth zone of the placentas and the endoplasmic reticulum in the spongiotrophoblasts were collapsed. The gene profiles in the placenta showed downregulation of antioxidants, ROS metabolism and oxidative stress response genes. In conclusion, intact A1M expression is necessary for the maintenance of normal kidney, heart as well as placental structure and function for a normal pregnancy adaptation.

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Novel Insights Into the Role of Glycans in the Pathophysiology of Glomerular Endotheliosis in Preeclampsia

Cited by 15 publications

References 93 publications

Pathogenesis of COVID‐19 described through the lens of an undersulfated and degraded epithelial and endothelial glycocalyx

Pathogenesis of COVID‐19 described through the lens of an undersulfated and degraded epithelial and endothelial glycocalyx

Can Endothelial Glycocalyx Be a Major Morphological Substrate in Pre-Eclampsia?

Pregnant alpha-1-microglobulin (A1M) knockout mice exhibit features of kidney and placental damage, hemodynamic changes and intrauterine growth restriction

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