Abstract
Background
Among strategies to reduce the remaining risk of cardiovascular disease, interest
has focused on using infusions of synthetic high-density lipoprotein (sHDL).
Methods
New Zealand rabbits underwent a perivascular injury at both carotids and were randomly
allocated into 2 protocols: (1) a single-dose study, where rabbits were treated with
a single infusion of sHDL containing a trimeric form of human apoA-I (TN-sHDL, 200
mg/kg) or with Placebo; (2) a multiple-dose study, where 4 groups of rabbits were
treated 5 times with Placebo or TN-sHDL at different doses (8, 40, 100 mg/kg). Plaque
changes were analysed in vivo by intravascular ultrasound. Blood was drawn from rabbits for biochemical analyses
and cholesterol efflux capacity evaluation.
Results
In both protocols, atheroma volume in the Placebo groups increased between the first
and the second intravascular ultrasound evaluation. A stabilization or a slight regression
was instead observed vs baseline in the TN-sHDL-treated groups (P < 0.005 vs Placebo after infusion). TN-sHDL treatment caused a sharp rise of plasma-free
cholesterol levels and a significant increase of total cholesterol efflux capacity.
Histologic analysis of carotid plaques showed a reduced macrophage accumulation in
TN-sHDL-treated rabbits compared with Placebo (P < 0.05).
Conclusions
Our results demonstrate that acute and subacute treatments with TN-sHDL are effective
in stabilizing atherosclerotic plaques in a rabbit model. This effect appears to be
related to a reduced intraplaque accumulation of inflammatory cells. Besides recent
failures in proving its efficacy, sHDL treatment remains a fascinating therapeutic
option for the reduction of cardiovascular risk.
Résumé
Contexte
Parmi les stratégies visant à réduire le risque résiduel de maladie cardiovasculaire,
la perfusion de lipoprotéines de haute densité synthétiques (HDLs) suscite un grand
intérêt.
Méthodologie
Des lapins de Nouvelle-Zélande ont subi une lésion périvasculaire aux deux carotides
et ont été répartis de façon aléatoire dans deux protocoles : (1) une étude portant
sur une seule dose, au cours de laquelle les lapins ont reçu une seule perfusion de
HDLs renfermant une forme trimère d’apoA1 humaine (TN-HDLs, 200 mg/kg) ou un placebo;
ou (2) une étude portant sur diverses doses, au cours de laquelle 4 groupes de lapins
ont été traités à 5 reprises par un placebo ou par des perfusions de TN-HDLs à différentes
doses (8, 40, 100 mg/kg). L’évolution des plaques a été analysée in vivo par échographie
intravasculaire. Des échantillons de sang ont été prélevés pour les analyses biochimiques
et l’évaluation de la capacité d’efflux du cholestérol.
Résultats
Dans les deux protocoles, le volume de l’athérome dans les groupes sous placebo a
augmenté entre la première et la seconde évaluation par échographie intravasculaire.
Par contre, dans les groupes ayant reçu les perfusions de TN-HDLs, une stabilisation
ou une légère régression des plaques (p < 0,05 comparativement au placebo après perfusion) ont été observées par rapport
aux valeurs initiales. Le traitement par TN-HDLs a été associé à une élévation marquée
du taux plasmatique de cholestérol libre et à une augmentation significative de la
capacité d’efflux du cholestérol total. Les analyses histologiques des plaques dans
les carotides ont révélé une diminution de l’accumulation de macrophages chez les
lapins ayant reçu des perfusions de TN-HDLs comparativement à ceux sous placebo (p < 0,05).
Conclusions
Nos résultats montrent que les traitements aigus et subaigus par TN-HDLs stabilisent
efficacement les plaques d’athérosclérose dans un modèle de lapin. Cet effet semble
lié à une accumulation moindre de cellules inflammatoires dans les plaques. Malgré
des résultats récents n’ayant pas corroboré son efficacité, le traitement par les
HDLs demeure une option thérapeutique fascinante dans la réduction du risque cardiovasculaire.
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Article info
Publication history
Published online: May 30, 2019
Accepted:
May 23,
2019
Received:
October 24,
2018
Footnotes
See page 1406 for disclosure information.
Identification
Copyright
© 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
