Nitric oxide and endothelin after lipid apheresis - a pilot study.
OBJECTIVE
Patients with the heterozygous form of familial hypercholesterolemia (FH) display an early onset of atherosclerosis due to disturbed vascular-endothelial function. Whether the improvements of endothelial function after lipid apheresis are mediated by increased NO-production or by an altered turnover of vasoconstrictors such as ET-1 is still unknown. This was the onset of the present study.


METHODS
Patients with FH and advanced atherosclerosis receiving regular LDL apheresis at 1 to 3 weeks were recruited. Lipids, L-arginine (L-Arg), L-hydroxyarginine (NHA), L-citrulline as well as big endothelin (Big-ET) and endothelin (ET-1) were measured after DALI, HELP and TheraSorb apheresis.


RESULTS
17 patients with severe FH aged 55.6 years (mean) received a total of 30 treatments. TC, LDL-C, HDL-C, TG and TC / HDL-C ratio were reduced (55, 70, 9, 48, and 52%; p<0.01) with no differences between apheresis systems. L-Arg was reduced after apheresis (HELP -18.0%, DALI -26.5%; Therasorb -7.6%) and returned to baseline after 2 h. Big-ET (p<0.01) and ET-1 were found to be increased directly and 2 hours after apheresis with HELP while transiently decreasing with DALI and Therasorb.


CONCLUSIONS
Improvement of endothelial function after apheresis seems to have multifaceted causes. The further elucidation of the interrelationship between endothelial dysfunction and restricted NO synthesis, as addressed in this study by measuring L-NHA, L-Arg, L-Cit, ET-1 and Big-ET will be necessary in the future.
Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden. jan.beyer@uniklinikum-dresden.de
J
J
Beyer-Westendorf
W
W
Seitz
N
N
Jabs
P
P
Bramlage
E
E
Kuhlisch
U
U
Julius
S R
SR
Bornstein
S M
SM
Schellong
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001120:Arginine / Q000097:blood; D050197:Atherosclerosis / Q000097:blood / Q000235:genetics / Q000628:therapy*; D015415:Biomarkers / Q000097:blood; D001781:Blood Component Removal / Q000379:methods; D016022:Case-Control Studies; D002956:Citrulline / Q000097:blood; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000235:genetics / Q000628:therapy*; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D010865:Pilot Projects; D016896:Treatment Outcome
D015415:Biomarkers; D019332:Endothelin-1; D008055:Lipids; D002956:Citrulline; D009569:Nitric Oxide; D001120:Arginine