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Published on: October 12, 2017
Elevated HDL cholesterol is functionally ineffective in cardiac transplant recipients: evidence for impaired reverse
Dmitri Sviridov1, Jaye Chin-Dusting, Paul Nestel
1Baker Heart Research Institute, Melbourne, Victoria, Australia. dmitri.sviridov@baker.edu.au
Insights
High high-density lipoprotein (HDL) in heart transplant patients may not be cardioprotective. This study found that high HDL levels are linked to dysfunctional HDL particles, suggesting a lack of heart protection.
Area of Science:
- Cardiovascular Science
- Lipid Metabolism
- Transplant Immunology
Background:
- Cardiac transplant recipients often exhibit elevated plasma high-density lipoprotein (HDL) levels.
- The cardioprotective role of these high HDL levels in this specific patient population remains unclear.
Purpose of the Study:
- To investigate whether high plasma HDL levels in cardiac transplant recipients are associated with a cardioprotective profile.
- To compare reverse cholesterol transport and endothelial function in relation to HDL levels.
Main Methods:
- Compared 25 cardiac transplant recipients (11 low HDL, 14 high HDL) and 26 healthy controls.
- Assessed parameters of reverse cholesterol transport (cholesterol efflux) and endothelial function.
- Analyzed lipid profiles, including triglycerides, prebeta1-HDL, and HDL particle size.
Main Results:
- High HDL patients showed lower triglycerides and prebeta1-HDL, with a higher proportion of large HDL particles.
- Non-ABCA1-dependent cholesterol efflux was reduced in high HDL patients compared to low HDL patients.
- No significant differences in endothelial function (vascular responses) were observed based on HDL levels.
Conclusions:
- Hyperalphalipoproteinemia in cardiac transplant recipients is associated with partially dysfunctional HDL.
- Elevated HDL levels in this group may not provide the expected cardioprotection.
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.
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