TY  - JOUR
A1  - Krieter, Detlef H.
A1  - Jeyaseelan, Jarline
A1  - Rüth, Marieke
A1  - Lemke, Horst-Dieter
A1  - Wanner, Christoph
A1  - Drechsler, Christiane
T1  - Clinical hemocompatibility of double-filtration lipoprotein apheresis comparing polyethersulfone and ethylene-vinyl alcohol copolymer membranes
JF  - Artificial Organs
N2  - Activation of the complement system and leukocytes by blood–membrane interactions may further promote arteriosclerosis typically present in patients on lipoprotein apheresis. As clinical data on the hemocompatibility of lipoprotein apheresis are scarce, a controlled clinical study comparing two different types of plasma separation and fractionation membranes used in double-filtration lipoprotein apheresis was urgently needed, as its outcome may influence clinical decision-making. In a prospective, randomized, crossover controlled trial, eight patients on double-filtration lipoprotein apheresis were subjected to one treatment with recent polyethersulfone (PES) plasma separation and fractionation membranes and one control treatment using a set of ethylene-vinyl alcohol copolymer (EVAL) membranes. White blood cell (WBC) and platelet (PC) counts, complement factor C5a and thrombin–antithrombin III (TAT) concentrations were determined in samples drawn at defined times from different sites of the extracorporeal blood and plasma circuit. With a nadir at 25 minutes, WBCs in EVAL decreased to 33.5 ± 10.7% of baseline compared with 63.8 ± 22.0% at 20 minutes in PES (P < .001). The maximum C5a levels in venous blood reentering the patients were measured at 30 minutes, being 30.0 ± 11.2 µg/L with EVAL and 12.3 ± 9.0 µg/L with PES (P < .05). The highest C5a concentrations were found in plasma after the plasma filters (EVAL 56.1 ± 22.0 µg/L at 15 minutes vs PES 23.3 ± 15.2 µg/L at 10 minutes; P < .001). PC did not significantly decrease over time with both membrane types, whereas TAT levels did not rise until the end of the treatment without differences between membranes. Regarding lipoprotein(a) and low-density lipoprotein (LDL) cholesterol removal, both membrane sets performed equally. Compared with EVAL, PES membranes cause less leukocyte and complement system activation, the classical parameters of hemocompatibility of extracorporeal treatment procedures, at identical treatment efficacy. Better hemocompatibility may avoid inflammation-promoting effects through blood–material interactions in patients requiring double-filtration lipoprotein apheresis.
KW  - lipoprotein(a)
KW  - biocompatibility
KW  - fractionation membranev
KW  - hypercholesterolemia
KW  - LDL cholesterol
KW  - lipoprotein apheresis
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258307
VL  - 45
IS  - 9
ER  - 
TY  - JOUR
A1  - Kraft, Peter
A1  - Schuhmann, Michael K.
A1  - Garz, Cornelia
A1  - Jandke, Solveig
A1  - Urlaub, Daniela
A1  - Mencl, Stine
A1  - Zernecke, Alma
A1  - Heinze, Hans-Jochen
A1  - Carare, Roxana O.
A1  - Kleinschnitz, Christoph
A1  - Schreiber, Stefanie
T1  - Hypercholesterolemia induced cerebral small vessel disease
JF  - PLoS ONE
N2  - Background
While hypercholesterolemia plays a causative role for the development of ischemic stroke in large vessels, its significance for cerebral small vessel disease (CSVD) remains unclear. We thus aimed to understand the detailed relationship between hypercholesterolemia and CSVD using the well described Ldlr\(^{−/-}\) mouse model.

Methods
We used Ldlr\(^{−/-}\) mice (n = 16) and wild-type (WT) mice (n = 15) at the age of 6 and 12 months. Ldlr\(^{−/-}\) mice develop high plasma cholesterol levels following a high fat diet. We analyzed cerebral capillaries and arterioles for intravascular erythrocyte accumulations, thrombotic vessel occlusions, blood-brain barrier (BBB) dysfunction and microbleeds.

Results
We found a significant increase in the number of erythrocyte stases in 6 months old Ldlr\(^{−/-}\) mice compared to all other groups (P < 0.05). Ldlr\(^{−/-}\) animals aged 12 months showed the highest number of thrombotic occlusions while in WT animals hardly any occlusions could be observed (P < 0.001). Compared to WT mice, Ldlr\(^{−/-}\) mice did not display significant gray matter BBB breakdown. Microhemorrhages were observed in one Ldlr\(^{−/-}\) mouse that was 6 months old. Results did not differ when considering subcortical and cortical regions.

Conclusions
In Ldlr\(^{−/-}\) mice, hypercholesterolemia is related to a thrombotic CSVD phenotype, which is different from hypertension-related CSVD that associates with a hemorrhagic CSVD phenotype. Our data demonstrate a relationship between hypercholesterolemia and the development of CSVD. Ldlr\(^{−/-}\) mice appear to be an adequate animal model for research into CSVD.
KW  - hypercholesterolemia
KW  - cerebral small vessel disease
KW  - mouse model
KW  - histology
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170493
VL  - 12
IS  - 8
ER  -