TY  - JOUR
A1  - Tsuprykov, Oleg
A1  - Chaykovska, Lyubov
A1  - Kretschmer, Axel
A1  - Stasch, Johannes-Peter
A1  - Pfab, Thiemo
A1  - Krause-Relle, Katharina
A1  - Reichetzeder, Christoph
A1  - Kalk, Philipp
A1  - Adamski, Jerzy
A1  - Hocher, Berthold
T1  - Endothelin-1 overexpression improves renal function in eNOS knockout mice
JF  - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology
N2  - Background/Aims: To investigate the renal phenotype under conditions of an activated renal ET-1 system in the status of nitric oxide deficiency, we compared kidney function and morphology in wild-type, ET-1 transgenic (ET+/+), endothelial nitric oxide synthase knockout (eNOS-/-) and ET+/+eNOS-/- mice. Methods: We assessed blood pressure, parameters of renal morphology, plasma cystatin C, urinary protein excretion, expression of genes associated with glomerular filtration barrier and tissue remodeling, and plasma metabolites using metabolomics. Results: eNOS-/- and ET+/+eNOS-/- mice developed hypertension. Osteopontin, albumin and protein excretion were increased in eNOS-/- and restored in ET+/+eNOS-/- animals. All genetically modified mice developed renal interstitial fibrosis and glomerulosclerosis. Genes involved in tissue remodeling (serpinel, TIMP1, Collal, CCL2) were up-regulated in eNOS-/-, but not in ET+/+eNOS-/- mice. Plasma levels of free carnitine and acylcarnitines, amino acids, diacyl phosphatidylcholines, lysophosphatidylcholines and hexoses were descreased in eNOS-/- and were in the normal range in ET+/+eNOS-/- mice. Conclusion: eNOS-/- mice developed renal dysfunction, which was partially rescued by ET-1 overexpression in eNOS-/- mice. The metabolomics results suggest that ET-1 overexpression on top of eNOS knockout is associated with a functional recovery of mitochondria (rescue effect in 13-oxidation of fatty acids) and an increase in antioxidative properties (normalization of monounsaturated fatty acids levels). (C) 2015 The Author(s) Published by S. Karger AG, Basel
KW  - Chronic kidney disease
KW  - Endothelial nitric oxide synthase
KW  - Endothelin
KW  - Mice
KW  - Nitric oxide
Y1  - 2015
U6  - https://doi.org/10.1159/000438516
SN  - 1015-8987
SN  - 1421-9778
VL  - 37
IS  - 4
SP  - 1474
EP  - 1490
PB  - Karger
CY  - Basel
ER  - 
TY  - JOUR
A1  - Kumar, Reddi K.
A1  - Heuchel, Matthias
A1  - Kratz, Karl
A1  - Lendlein, Andreas
A1  - Jankowski, Joachim
A1  - Tetali, Sarada D.
T1  - Effects of extracts prepared from modified porous poly(ether imide) microparticulate absorbers on cytotoxicity, macrophage differentiation and proinflammatory behavior of human monocytic (THP-1) cells
JF  - Clinical hemorheology and microcirculation : blood flow and vessels
N2  - Remaining uremic toxins in the blood of chronic renal failure patients represent one central challenge in hemodialysis therapies. Highly porous poly(ether imide) (PEI) microparticles have been recently introduced as candidate absorber materials, which show a high absorption capacity for uremic toxins and allow hydrophilic surface modification suitable for minimization of serum protein absorption. In this work, the effects of extracts prepared from PEI microparticles modified by nucleophilic reaction with low molecular weight polyethylene imine (Pei) or potassium hydroxide (KOH), on human monocytic (THP-1) cells are studied. The obtained results suggested that the extracts of Pei and KOH modified PEI absorbers have no negative effect on THP-1 cell viability and do not initiate the critical differentiation towards macrophages. The extracts did not enhance transcript or protein levels of investigated proinflammatory markers in THP-1 cells, namely, TNF alpha, MCP1, IL6 and IL8. Based on these findings such modified PEI microparticles should be qualified for further pre-clinical evaluation i.e. in an in vivo animal experiment.
KW  - Chronic kidney disease
KW  - hemodialysis
KW  - Inflammation
KW  - Porous poly(ether imide) microparticulate absorbers
KW  - THP-1 cells
KW  - Uremic toxins
Y1  - 2018
U6  - https://doi.org/10.3233/CH-189112
SN  - 1386-0291
SN  - 1875-8622
VL  - 69
IS  - 1-2
SP  - 175
EP  - 185
PB  - IOS Press
CY  - Amsterdam
ER  -