Elevated HDL cholesterol is functionally ineffective in cardiac transplant recipients: evidence for impaired reverse cholesterol transport.
BACKGROUND
Cardiac transplant recipients frequently have high plasma HDL levels but it is unclear whether these promote a cardioprotective profile.


METHODS
Parameters of reverse cholesterol transport and endothelial function were compared in 25 cardiac transplant recipients with low (<1.4 mmol/L; n=11) or high (>1.4 mmol/L; n=14) plasma levels of HDL and in a reference healthy group.


RESULTS
Patients with high HDL had lower levels of triglyceride and prebeta1-HDL and a higher proportion of large HDL particles. When normalized to apoA-I content, non-ABCA1-dependent cholesterol efflux from RAW 264.7 macrophage cells to plasma from high HDL patients was 33% lower when compared to plasma from patients with low HDL, whereas ABCA1-dependent cholesterol efflux was not impaired. Forearm vascular responses to acetylcholine and sodium nitroprusside were not influenced by HDL levels in these patients. Compared to a reference healthy group (n=26), cardiac transplant recipients had higher levels of triglyceride, lower levels of prebeta1-HDL and LCAT, and lower activities of cholesteryl ester transfer protein and phospholipid transfer protein.


CONCLUSIONS
Hyperalphalipoproteinaemia in cardiac transplant recipients is associated with the formation of partially dysfunctional HDL. We conclude that high levels of HDL may not confer cardioprotection in this group of patients.
Baker Heart Research Institute, Melbourne, Victoria, Australia. dmitri.sviridov@baker.edu.au
Dmitri
D
Sviridov
Jaye
J
Chin-Dusting
Paul
P
Nestel
Bronwyn
B
Kingwell
Anh
A
Hoang
Beata
B
Olchawa
Jennifer
J
Starr
Anthony
A
Dart
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood; D001692:Biological Transport; D002784:Cholesterol / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D006951:Hyperlipoproteinemias / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology
D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D009599:Nitroprusside; D002784:Cholesterol; D000109:Acetylcholine