Androgen deprivation therapy improves the in vitro capacity of high-density lipoprotein (HDL) to receive cholesterol and other lipids in patients with prostate carcinoma

Cicero P Albuquerque,Roberto Kalil Filho,Willian C Nahas,Josefa H Lima,Rafael F Coelho,Ana Elisa M Martinelli,Carlos V Serrano,Fatima R Freitas,Raul C Maranhão

doi:10.1186/s12944-020-01305-8

Abstract

BackgroundAndrogen deprivation therapy (ADT) is widely used in the treatment of testosterone-dependent prostate carcinomas. ADT often increases plasma LDL and HDL cholesterol and triglycerides. The aim was to test whether ADT changes the transfer of lipids to HDL, an important aspect of this metabolism and HDL protective functions, and related parameters.MethodsSixteen volunteers with advanced prostate carcinoma submitted to pharmacological ADT or orchiectomy had plasma collected shortly before and after 6 months of ADT. In vitro transfer of lipids to HDL was performed by incubating plasma with donor emulsion containing radioactive lipids by 1 h at 37 °C. After chemical precipitation of apolipoprotein B-containing lipoprotein, the radioactivity of HDL fraction was counted.ResultsADT reduced testosterone to nearly undetectable levels and markedly diminished PSA. ADT increased the body weight but glycemia, triglycerides, LDL and HDL cholesterol, HDL lipid composition and CETP concentration were unchanged. However, ADT increased the plasma unesterified cholesterol concentration (48 ± 12 vs 56 ± 12 mg/dL, p = 0.019) and LCAT concentration (7.15 ± 1.81 vs 8.01 ± 1.55μg/mL, p = 0.020). Transfer of unesterified (7.32 ± 1.09 vs 8.18 ± 1.52%, p < 0.05) and esterified cholesterol (6.15 ± 0.69 vs 6.94 ± 1.29%, p < 0.01) and of triglycerides (6.37 ± 0.43 vs 7.18 ± 0.91%, p < 0.001) to HDL were increased after ADT. Phospholipid transfer was unchanged.ConclusionIncrease in transfer of unesterified and esterified cholesterol protects against cardiovascular disease, as shown previously, and increased LCAT favors cholesterol esterification and facilitates the reverse cholesterol transport. Thus, our results suggest that ADT may offer anti-atherosclerosis protection by improving HDL functional properties. This could counteract, at least partially, the eventual worse effects on plasma lipids.

Highlights

Androgen deprivation therapy (ADT), as achieved by both pharmacological and surgical castration, is an efficient and widely used therapeutic tool for the control of testosterone-dependent prostate carcinomas
Our results suggest that ADT may offer anti-atherosclerosis protection by improving high-density lipoprotein (HDL) functional properties
Cholesterol from other lipoproteins and from the cells transferred to HDL is esterified in this lipoprotein fraction by lecithin cholesterol acyl transferase (LCAT) using apolipoprotein A-I, the main HDL apo, as co-factor [6]

Summary

Introduction

Androgen deprivation therapy (ADT), as achieved by both pharmacological and surgical castration, is an efficient and widely used therapeutic tool for the control of testosterone-dependent prostate carcinomas. Esterification of cholesterol stabilizes the cholesterol plasma pool and drives the reverse cholesterol transport, so that the rates of transfer of cholesterol to HDL may be important to HDL functional role [6]. HDL has several protective actions, such as those of anti-oxidation, vasodilation, anti-inflammatory, anti-apoptotic, anti-thrombotic, anti-infectious actions and is a major transporter of microRNA’s that regulates several metabolic processes [4, 6]. In this setting, the HDL-cholesterol levels do not predict the full protective role of the lipoprotein and functional tests of the lipoprotein have been developed. Androgen deprivation therapy (ADT) is widely used in the treatment of testosterone-dependent prostate carcinomas. The aim was to test whether ADT changes the transfer of lipids to HDL, an important aspect of this metabolism and HDL protective functions, and related parameters

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