Activated NF-κB/Nrf2 and Wnt/β-catenin pathways are associated with lipid metabolism in CKD patients with microalbuminuria and macroalbuminuria

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2019, Volume and Issue: 1865(9), P. 2317 - 2332

Published: May 16, 2019

Language: Английский

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Albumin is an interface between blood plasma and cell membrane, and not just a sponge

Clinical Kidney Journal, Journal Year: 2021, Volume and Issue: 15(4), P. 624 - 634

Published: Oct. 1, 2021

Albumin is the most abundant protein in blood plasma and acts as a carrier for many circulating molecules. Hypoalbuminaemia, mostly caused by either renal or liver disease malnutrition, can perturb vascular homeostasis involved development of multiple diseases. Here we review four functions albumin consequences hypoalbuminaemia on homeostasis. (i) main determinant colloid osmotic pressure. Hypoalbuminaemia was therefore thought to be mechanism oedema nephrotic syndrome (NS), however, experimental studies showed that intrarenal mechanisms rather than determine formation and, particular, maintenance oedema. (ii) an interface between lysophosphatidylcholine (LPC) factors (lipoproteins erythrocytes) endothelium. Consequently, results higher LPC levels lipoproteins erythrocyte membrane, thereby increasing atherosclerotic properties low-density lipoprotein viscosity, respectively. Furthermore, dose-dependently restores LPC-induced inhibition vasodilation. (iii) impacts nitric oxide (NO) signalling directly NO production endothelial cells, leading reduced sensitivity smooth muscle cells. (iv) Lastly, binds free fatty acids (FFAs). FFAs induce cell apoptosis, uncouple synthase decrease endothelium-dependent Unbound increase reactive oxygen species mitochondrial uncoupling types hypertriglyceridemia NS. In conclusion, circulation impairs aspects function may underlie association with adverse outcomes. However, not key These insights have therapeutic implications.

Language: Английский

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Proprotein convertase subtilisin/kexin type 9 targets megalin in the kidney proximal tubule and aggravates proteinuria in nephrotic syndrome

Kidney International, Journal Year: 2023, Volume and Issue: 104(4), P. 754 - 768

Published: July 3, 2023

Proteinuria is a prominent feature of chronic kidney disease. Interventions that reduce proteinuria slow the progression disease and associated risk cardiovascular Here, we propose mechanistic coupling between proprotein convertase subtilisin/kexin type 9 (PCSK9), regulator cholesterol therapeutic target in PCSK9 undergoes glomerular filtration captured by megalin, receptor responsible for driving protein reabsorption proximal tubule. Accordingly, megalin-deficient mice patients carrying megalin pathogenic variants (Donnai Barrow syndrome) were characterized elevated urinary excretion. Interestingly, knockout displayed increased while overexpression resulted its reduction. Furthermore, promoted trafficking to lysosomes cultured tubule cells, suggesting negative megalin. This effect can be accelerated under conditions since either genetic destruction barrier podocin or minimal change (a common cause nephrotic enhanced tubular uptake Pharmacological inhibition reducing albumin excretion mice. Thus, damage increases concomitantly degradation, resulting escalated proteinuria.

Language: Английский

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Exploring the nexus: The place of kidney diseases within the cardiovascular-kidney-metabolic syndrome spectrum

European Journal of Internal Medicine, Journal Year: 2024, Volume and Issue: 127, P. 1 - 14

Published: July 19, 2024

Language: Английский

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Kidney function is associated with an altered protein composition of high-density lipoprotein

Kidney International, Journal Year: 2017, Volume and Issue: 92(6), P. 1526 - 1535

Published: July 26, 2017

Language: Английский

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