Effect of Selective Androgen Receptor Modulator on Cholesterol Efflux Capacity, Size, and Subspecies of HDL Particles.
J Endocr Soc
; 6(8): bvac099, 2022 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-35822201
ABSTRACT
Context Selective androgen receptor modulators (SARMs), because of their preferential muscle vs prostate selectivity, are being developed for muscle-wasting conditions. Oral SARMs suppress high-density lipoprotein cholesterol (HDL-C) but their effects on functional capacity and atherogenic potential of HDL particles are unknown. Objective:
To determine the effects of an oral SARM (OPK-88004) on cholesterol efflux capacity, HDL particle number and size, apolipoprotein particle number and size and HDL subspecies.Methods:
We measured cholesterol efflux capacity (CEC); HDL particle number and size; APOB; APOA1; and protein-defined HDL subspecies associated with coronary heart disease (CHD) risk in men, who had undergone prostatectomy for low-grade prostate cancer during 12-week treatment with placebo or 1, 5, or 15 mg of an oral SARM (OPK-88004).Results:
SARM significantly suppressed HDL-C (Pâ <â .001) but HDL particle size did not change significantly. SARM had minimal effect on CEC of HDL particles (changeâ +â 0.016, -0.036, +0.070, and -0.048%/µmol-HDL/L-1 at 0, 1, 5, and 15 mg SARM, Pâ =â .045). SARM treatment suppressed APOAI (Pâ <â .001) but not APOB (Pâ =â .077), and reduced APOA1 in HDL subspecies associated with increased (subspecies containing α2-macroglobulin, complement C3, or plasminogen) as well as decreased (subspecies containing APOC1 or APOE) CHD risk; relative proportions of APOA1 in these HDL subspecies did not change. SARM increased hepatic triacylglycerol lipase (HTGL) (Pâ <â .001).Conclusion:
SARM treatment suppressed HDL-C but had minimal effect on its size or cholesterol efflux function. SARM reduced APOA1 in HDL subspecies associated with increased as well as decreased CHD risk. SARM-induced increase in HTGL could contribute to HDL-C suppression. These data do not support the simplistic notion that SARM-associated suppression of HDL-C is necessarily proatherogenic; randomized trials are needed to determine SARM's effects on cardiovascular events.
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MEDLINE
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Ano de publicação:
2022
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Article