Human free apolipoprotein A-I and artificial pre-beta-high-density lipoprotein inhibit eNOS activity and NO release.
Little is known about the effects of human free apolipoprotein A-I (Free-Apo A-I) and pre-beta-high density lipoprotein (pre-beta-HDL) on the endothelium function. In this study, we have investigated the effects of Free-Apo A-I and artificial pre-beta-HDL on endothelial NO synthase (eNOS) activity and on NO production by endothelial cells. Free-Apo A-I drastically inhibited NO production in human umbilical cord vein endothelial cells (HUVECs) and eNOS activity in bovine aortic endothelial cells (BAECs). Pre-beta-HDL and serum from human apolipoprotein A-I transgenic rabbits inhibited eNOS activity in BAECs but HDL3 did not. Free-Apo A-I displaced eNOS from BAEC plasma membrane towards intracellular pools without affecting eNOS activity and eNOS mass in BAEC crude homogenates. Free-Apo A-I and HDL3 did not decrease either caveolin bound to BAEC plasma membrane or caveola cholesterol content. As previously described, we showed that HDL3 directly induced endothelium-dependent relaxation of rings from rat aorta. We observed that pre-beta-HDL significantly decreased endothelium-dependent relaxation of rat aortic rings ex vivo.
Briand
Olivier
O
Department of Research on Atherosclerosis, Inserm UMR545, Institut Pasteur de Lille et Faculté des Sciences Pharmaceutiques et Biologiques, Université de Lille 2, 3 rue du Professeur Laguesse, BP 83 59006 Lille Cedex, France.
Nizard
Françoise Martin
FM
David-Dufilho
Monique
M
Six
Isabelle
I
Lestavel
Sophie
S
Brunet
Annie
A
Fruchart
Jean-Charles
JC
Torpier
Gérard
G
Bordet
Régis
R
Clavey
Véronique
V
Duriez
Patrick
P
D000818:Animals; D030801:Animals, Genetically Modified; D001011:Aorta / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000494:pharmacology*; D002417:Cattle; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology; D053442:High-Density Lipoproteins, Pre-beta; D006801:Humans; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008297:Male; D009126:Muscle Relaxation / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D014470:Umbilical Cord / Q000378:metabolism
D016632:Apolipoprotein A-I; C495540:CAV1 protein, human; C495537:Cav1 protein, rat; D051242:Caveolin 1; D022461:Caveolins; D053442:High-Density Lipoproteins, Pre-beta; D008075:Lipoproteins, HDL; D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat