Ways and Means of Cellular Reconditioning for Kidney Regeneration

Abstract Background: Mitochondrial, lysosomal, and peroxisomal dysfunction; defective autophagy; mitophagy; and pexophagy, as well as the loss of glycocalyx integrity are known contributors to initiation and progression of diverse kidney diseases. Those cellular organelles are tightly interactive in health, and during development of a disease, damage in one may propagate to others. By extension, it follows that restoring an individual defect may culminate in a broader restorative spectrum and improvement of cell and organ functions. Summary: A novel strategy of reconditioning cellular organellar dysfunction, which we define as refurbishment of pathogenically pivotal intra- or extracellular elements, damaged in the course of disease

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Mutations in the heparan sulfate backbone elongating enzymes EXT1 and EXT2 have no major effect on endothelial glycocalyx and the glomerular filtration barrier

Abstract In this study, the effect of heterozygous germline mutations in the heparan sulfate (HS) glycosaminoglycan chain co-polymerases EXT1 and EXT2 on glomerular barrier function and the endothelial glycocalyx in humans is investigated. Heparan sulfate (HS) glycosaminoglycans are deemed essential to the glomerular filtration barrier, including the glomerular endothelial glycocalyx. Animal studies have shown that loss of HS results in a thinner glycocalyx. Also, decreased glomerular HS expression is observed in various proteinuric renal diseases in humans. A case report of a patient with an EXT1 mutation indicated that this could result in a specific renal phenotype. This patient suffered

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Microvascular rarefaction in patients with cerebrovascular events

Abstract Capillary density rarefaction and endothelial dysfunction contribute to chronic hypoperfusion and cerebral small vessel disease. Previous animal experiments revealed spatiotemporal microvascular remodeling directing post-stroke brain reorganization. We hypothesized that microcirculatory changes during acute cerebrovascular events could be reflected systemically and visualized sublingually. In a prospective observational trial in vivo sublingual sidestream darkfield videomicroscopy was performed in twenty-one patients with either acute stroke (n = 13 ischemic, n = 1 ischemic with hemorrhagic transformation and n = 2 hemorrhagic stroke) or transitory ischemic attacks (n = 5) within 24 h after hospital admission and compared to an age- and sex-matched

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Endothelial glycocalyx and microvascular perfusion are associated with carotid intima-media thickness and impaired myocardial deformation in psoriatic disease

Abstract Psoriatic disease is associated with vascular and myocardial dysfunction. We aimed to evaluate endothelial glycocalyx barrier properties and microvascular perfusion in psoriatic patients, as well as their correlation with carotid intima-media thickness (cIMT) and markers of left ventricular (LV) myocardial deformation. We examined 297 psoriatic patients and 150 controls, adjusted for age, sex, and atherosclerotic risk factors. The severity of psoriatic disease was estimated using the psoriasis area and severity index (PASI). Perfused boundary region (PBR), a marker of glycocalyx barrier function, was measured non-invasively in sublingual microvessels with a diameter 5–25 μm using Sidestream Dark Field camera (Microscan, GlycoCheck).

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Association of Gestational Diabetes With Subclinical Cardiovascular Disease on Echocardiogram and Endothelial Function Testing

Abstract Introduction: Gestational diabetes mellitus (GDM) increases risk for cardiovascular disease (CVD). The subclinical cardiovascular structural and functional changes that contribute to long-term cardiovascular risk are unclear. Hypothesis: We hypothesized that GDM is associated with adverse cardiovascular remodeling, diastolic function abnormalities, and endothelial dysfunction at approximately a decade after delivery, thereby increasing CVD risk. Methods: We conducted a cross-sectional analysis of women from an existing cohort with abstracted clinical pregnancy data. Women attended a follow-up visit at a median of 9 years after delivery. Echocardiograms, Peripheral Arterial Tonometry (EndoPAT), glycocalyx analysis (GlycoCheck) and laboratory testing were conducted at the follow-up

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Impaired Endothelial Glycocalyx Predicts Adverse Outcome in Subjects Without Overt Cardiovascular Disease: a 6-Year Follow-up Study

Abstract We investigated whether disturbance of glycocalyx integrity is related with increased cardiovascular risk. In 600 healthy subjects, we measured perfused boundary region (PBR), a marker of glycocalyx integrity, in sublingual microvessels with diameter ranging 5–25 µm using a dedicated camera (Sideview Darkfield Imaging). Increased PBR indicates reduced glycocalyx thickness. We prospectively monitored the occurrence of cardiovascular events (MACE-death, myocardial infarction, and stroke) during a 6-year follow-up. Fifty-seven MACE were documented. Increased values of PBR5-25 predicted higher risk for MACE in a model including sex, age, hyperlipidemia, diabetes, hypertension, smoking, family history of coronary disease, treatment with ACEi/ARBs, or lipid-lowering

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