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

Jens Van De Wouw*, Jaap A. Joles

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

12 Citations (Scopus)
33 Downloads (Pure)


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

Original languageEnglish
Pages (from-to)624-634
Number of pages11
JournalClinical Kidney Journal
Issue number4
Publication statusPublished - Apr 2022

Bibliographical note

Funding Information:
This work was supported by a grant from the Netherlands CardioVascular Research Initiative, an initiative with support of the Dutch Heart Foundation [CVON2014-11 (RECONNECT)] and from the Dutch CardioVascular Alliance, an initiative with support of the Dutch Heart Foundation (Grant 2020B008; RECONNEXT).

Publisher Copyright:
© 2021 The Author(s).


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