Renal microvascular endothelial cell responses in sepsis-induced acute kidney injury

Grietje Molema*, Jan G Zijlstra, Matijs van Meurs, Jan A A M Kamps

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

12 Citaten (Scopus)
389 Downloads (Pure)

Samenvatting

Endothelial cells in the kidney microvasculature have an intrinsic molecular and phenotypic heterogeneity and respond to sepsis-induced acute kidney injury conditions in a segment-specific manner. This Review discusses the roles of these cells and the molecular systems that control endothelial functions in the development of sepsis-induced acute kidney injury.

Microvascular endothelial cells in the kidney have been a neglected cell type in sepsis-induced acute kidney injury (sepsis-AKI) research; yet, they offer tremendous potential as pharmacological targets. As endothelial cells in distinct cortical microvascular segments are highly heterogeneous, this Review focuses on endothelial cells in their anatomical niche. In animal models of sepsis-AKI, reduced glomerular blood flow has been attributed to inhibition of endothelial nitric oxide synthase activation in arterioles and glomeruli, whereas decreased cortex peritubular capillary perfusion is associated with epithelial redox stress. Elevated systemic levels of vascular endothelial growth factor, reduced levels of circulating sphingosine 1-phosphate and loss of components of the glycocalyx from glomerular endothelial cells lead to increased microvascular permeability. Although coagulation disbalance occurs in all microvascular segments, the molecules involved differ between segments. Induction of the expression of adhesion molecules and leukocyte recruitment also occurs in a heterogeneous manner. Evidence of similar endothelial cell responses has been found in kidney and blood samples from patients with sepsis. Comprehensive studies are needed to investigate the relationships between segment-specific changes in the microvasculature and kidney function loss in sepsis-AKI. The application of omics technologies to kidney tissues from animals and patients will be key in identifying these relationships and in developing novel therapeutics for sepsis.

Originele taal-2English
Pagina's (van-tot)95-112
Aantal pagina's18
TijdschriftNature Reviews Nephrology
Volume18
Nummer van het tijdschrift2
Vroegere onlinedatum19-okt-2021
DOI's
StatusPublished - feb-2022

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